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研究生：	黃暉庭 Huang, Hui-Ting
論文名稱：	攝取高脂誘導肥胖引發腦部微膠質細胞增生的機制性與藥理之探討 Mechanistic examination and pharmacological approach to study brain microgliosis in high fat diet-associated obesity
指導教授：	曾淑芬 Tzeng, Shun-Fen
學位類別：	博士 Doctor
系所名稱：	生物科學與科技學院 - 生命科學系 Department of Life Sciences
論文出版年：	2020
畢業學年度：	108
語文別：	英文
論文頁數：	81
中文關鍵詞：	神經發炎、寡突膠質細胞、微膠質細胞增生、介白素-33 、高脂飼料、脂多醣、三氟拉嗪
外文關鍵詞：	Neuroinflammation, Oligodendrocytes, Microgliosis, IL-33, HFD, LPS, TFP
相關次數：	點閱：91 下載：0
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肥胖為現今社會常見之代謝疾病，並增加罹患心血管病、第二型糖尿病、癌症甚至情感型疾病。神經發炎在肥胖的發展過程中扮演著至關重要的角色。下視丘為大腦中調控能量平衡與飲食的腦區。過去臨床研究與動物實驗中發現，肥胖個體的下視丘具有發炎情形。另有研究指出，去除下視丘內具免疫功能之微膠質細胞可以改善肥胖所造成的體重增加。過去我們實驗餵食C57BL/6小鼠2、3及4個月高脂飼料(high fat diet, HFD)，誘發下視丘弓狀核 (arcuate nucleus, ARC)內微膠質細胞增生(microgliosis)並導致由寡突膠質細胞（oligodendrocytes, OLs）構成髓鞘之完整性的缺失。在本項研究中，利用脂多醣（lipopolysaccharides, LPS）間歇性給予增強周邊發炎與藥物給予方式來探討下視丘內微膠質細胞對於OLs致病機轉與肥胖發展過程的作用。實驗結果首先發現餵養3和4個月HFD後，下視丘內星狀膠質細胞與OLs中警報蛋白-介白素33（interleukin-33, IL-33）表現量上升。另外，給予重組IL-33蛋白會破壞OLs形成之膜狀結構並降低髓鞘鹼性蛋白（myelin basic protein, MBP）表現量。這些發現指出IL-33對於長期HFD餵食之肥胖小鼠下視丘內OLs產生有害作用。

由於肥胖會引起周邊組織輕度發炎，因此透過增強周邊發炎程度觀察發炎對於肥胖所造成體重改變之影響。於餵食HFD期間的第1、2與8週透過腹腔注射給予LPS（1 mg / kg）。實驗結果顯示，與注入生理食鹽水組的HFD餵食之小鼠(HFD-Saline)相比，接受LPS注射的HFD餵食之小鼠(HFD-LPS)的體重並無明顯變化。有趣的是，透過高架十字迷宮（elavated plus maze, EPM）與開放場域測試（open fields test, OFT）觀察動物行為變化發現，間歇性LPS注射增加了正常飼料餵食五個月小鼠（Chow-LPS）的探索行為，但於HFD-LPS組別中受到抑制。此外，HFD餵食誘發ARC和伏隔核（nucleus accumbens. NAc）內的微膠質細胞活化於HFD-LPS組別中受到抑制。處理LPS所導致的基底外側杏仁核（basolateral amygdala, BLA）內微膠質細胞的活化於HFD-LPS組別同樣受到抑制。不同於微膠質細胞，HFD-LPS組別中ARC和BLA內星形膠質細胞形態生成增加。上述發現提供新的見解，不同免疫刺激共同作用下改變微膠質細胞對於單一刺激物的反應，進而改變大腦區域的發炎微環境並影響動物行為。篩選抗糖尿病藥物庫中抑制LPS誘導微膠質細胞活化之藥物，並選擇多巴胺D2受體拮抗劑-三氟拉嗪（TFP）。將餵食3個月HFD小鼠透過腹腔注射每天給予2 mg / kg TFP持續一個月，過程中持續餵食HFD。結果發現連續給予1個月TFP可以抑制HFD餵養小鼠下視丘內膠質細胞增生，但無法降低肥胖小鼠的體重和代謝指標異常。不過TFP可以降低HFD誘導肥胖小鼠的高血糖症。

總結上述研究結果，IL-33可能參與下視丘神經膠質細胞對於長期HFD餵食的反應。HFD攝食期間伴隨急性發炎並不會對肥胖小鼠體重產生影響，但改變微膠質細胞對於長期HFD餵養之敏感性。最後，抑制ARC內微膠質細胞作用不足以減少因長期HFD餵養所引起的體重增加。

Obesity is a common syndrome in the modern society, which increases the risk of several diseases, such as cardiovascular diseases, type II diabetes mellitus, cancers and even mood disorders. Neuroinflammation has been considered as a critical regulator in the development of obesity. The hypothalamus is a brain region, which regulates energy balance and ingestion. The clinical and animal studies indicate hypothalamic inflammation occurs in obese individuals. Moreover, evidence reveals that the ablation of hypothalamic microglia, a glial population as immune cells in central nervous system (CNS), can reduce the body weight of high fat diet (HFD)-fed animals. We have used eight-week old male C57BL/6 mouse model that received HFD feeding at 2, 3, and 4 months, which induced sustained microgliosis in hypothalamic arcuate nucleus (ARC) at the three time points and trigger the de-integrity of myelin produced by oligodendrocytes (OLs). In this study, we attempted to uncover the role of hypothalamic microglia in OL pathogenesis and obesity development through the enhancement of peripheral inflammation using intermittent administrations of lipopolysaccaride (LPS) or via pharmacological approach. The results first showed that interleukin-33 (IL-33), an alarm protein, widely detected in astrocytes and OLs in the hypothalamus, was upregulated after HFD-feeding for 3 and 4 months. The addition of recombinant IL-33 proteins into mature OLs impaired their morphology along the reduction of their mature marker, myelin basic protein (MBP). The findings suggest that IL-33 might exert the detrimental effect on hypothalamic OLs in obese mice receiving chronic HFD feeding.

Given the fact that obesity causes peripheral mild inflammation, we attempted to determine if the body weight was affected by enhanced peripheral inflammation in obese. We conducted the experiments that the intermittent administrations with LPS (1 mg/kg) via intraperitoneal (i.p.) injection at 1 week, 2 week and 8 week after HFD feeding. The results indicated that a nonsignificant change in the body weight was detected in HFD-fed mice receiving LPS injections (HFD-LPS) when compared to that of HFD-fed mice with Saline injections (HFD-Saline). Interestingly, examination of the animal behaviors through elevated plus maze (EPM) and open fields test (OFT) at 5 month after HFD feeding showed that intermittent LPS injections increased an exploratory behavior in Chow-fed mice (Chow-LPS) when compared to that observed in the Chow group with Saline injections (Chow-Saline). Yet, this behavior was inhibited in the HFD-LPS group. Moreover, HFD feeding-associated microglia activation in ARC and nucleus accumbens (NAc) was suppressed in the HFD-LPS group. LPS-induced microglia activation in basal lateral amygdala (BLA) was inhibited in the HFD-LPS group. Yet, astrocyte morphogenesis in ARC and BLA was enhanced in the HFD-LPS group. These findings give an insight that the co-stimulation of the distinct immune stimuli might modify microglia in response to one single stimulus, which can amend microenvironmental inflammation in the brain regions and alter the animal behavior.

Through examination of anti-diabetes library collection in the inhibition of LPS-induced microglia activation, trifluoperazine (TFP), a dopamine D2R antagonist, was selected and its daily application of 2 mg/kg per day via i.p. injection for 1 month into mice that have received HFD feeding for 3 months. The results indicated that TFP administration can suppress gliosis in the hypothalamus of HFD-fed mice, but did not lower down the body weight of the obese mice and abnormal metabolic index. Yet, HFD-induced hyperglycemia was reduced by TFP administration into obese mice.

In conclusion, the findings of our study are summarized as below. First, IL-33 could be involved in hypothalamic glial response to chronic HFD feeding. Second, the acute exposure to the potent inflammagen during HFD intake caused no effect on the body weight of obese mice, but primed microglia to modify their sensitivity to chronic HFD feeding. Third, the inhibition of ARC microglia is not sufficient for the reduction of the body weight gain induced by chronic HFD feeding.

Abstract in Chinese	I
Abstract	III
Acknowledgments	VI
Contents	VII
Abbreviations list	XI
Introduction	1
1-1. The Brain Regions Response to Obesity	2
1-2. Obesity-induced Inflammation in CNS	3
Peripheral inflammation in obesity	3
Obesity-induced CNS inflammation	5
1-3. The Effects of Neuroinflammation in Neurodegenerative Disease	8
1-4. Mood disorders and Brain inflammation	9
The brain regions involved in emotion	9
The Interaction Between Mood Disorders and Neuroinflammation	11
1-5. Metabolic syndromes and Mood disorders	12
Specific aims	14
Materials and Methods	15
2-1. Animals	15
2-2. Preparation of Primary Oligodendrocyte Precursor Cells (OPCs)	15
2-3. Preparation of Primary Microglia	16
2-4. Western blot analysis	17
2-5. Immunofluorescence staining	17
2-6. Cytokine detection and metabolic index in plasma	18
2-7. Animal behavior test	18
a. Elevated plus maze (EPM)	18
b. Open field test (OFT)	19
2-8. Microglia Number and Cell Body Analysis	19
2-9. Quantification of Oligodendrocyte Morphology	19
2-10. Quantitative real-time polymerase chain reaction (QPCR)	19
2-11. Statistical analysis	20
Results	21
3-1. Microglia activation induced by chronic HFD feeding in hypothalamic arcuate nucleus	.....................................................................................................................................................21
3-2. IL-33 in hypothalamus was increased by chronic HFD feeding.	22
3-3. Chronic HFD feeding attenuates early LPS administration-induced exploratory behaviors in mice.	23
3-4. Early LPS administrations in combination with chronic HFD feeding decreases microglia activation associated with in ARC, BLA and NAc	24
3-5. Early LPS administrations in combination with chronic HFD feeding decreases microglia activation associated with in ACC and Insula	25
3-6. Astrogliosis in ARC and BLA after early LPS administration in HFD-fed mice	26
3-7. Anti-inflammatory drugs effects on hypothalamic inflammation	27
Discussion	29
4-1. Inflammatory cytokines in hypothalamus after HFD feeding	29
4-2. What is mechanism of IL-33 to trigger HFD-induced disruption of myelin structure and oligodendrocytes?	30
4-3. Combination of LPS administration with chronic HFD-feeding eliminates inflammation response.	32
4-4. Hypothalamic inflammation in the development of obesity.	33
4-5. LPS-induced exploratory behaviors	34
4-6. Conclusion	35
References	37
Figures and Legends	53
Figure. 1 Expression of cytokines and chemokines in the hypothalamus of Chow and HFD-fed mice.	53
Figure. 2 Microglia activation induced by chronic HFD feeding in hypothalamic arcuate nucleus.	54
Figure. 3 Microglia activation induced by chronic HFD feeding in hypothalamic arcuate nucleus and median eminence.	55
Figure. 4 IL-33 in hypothalamus was increased by chronic HFD feeding.	57
Figure. 5 IL-33 expression after LM and IL-1β treatment in astrocytic conditioned medium (ACM) and oligodendrocytic conditioned medium (OCM).	58
Figure. 6 IL-33 induces the morphologic change of mouse OLs.	59
Figure. 7 IL-33 induces the morphologic change of rat OLs.	60
Figure. 8 The schematic diagram illustrates the experimental design and brain regions used for Iba1 and GFAP immunofluorescence (IF).	61
Figure. 9 Hypothalamic TNF-α and IL-1β levels were increased after the first LPS injection but no change on bodyweight.	62
Figure. 10 The plasma levels of TNF-α and IL-1β were increased by LPS injection in Chow or HFD-fed mice.	63
Figure. 11 Morphological changes of microglia in the hypothalamic arcuate nucleus after intermittent LPS administration in HFD-fed mice at 1, 2 and 8 week.	64
Figure. 12 Chronic HFD feeding attenuated the suppression of LPS-induced behavior in mice.	65
Figure. 13 Morphological alteration of microglia in the hypothalamic arcuate nucleus was induced by intermittent LPS administration in HFD-fed mice.	66
Figure. 14 Microglial activation in the BLA and NAc was attenuated by intermittent LPS administration and chronic HFD feeding.	67
Figure. 15 Microglial activation in the ACC and insula was attenuated by intermittent LPS administration and chronic HFD feeding.	69
Figure. 16 Enhanced astrocyte morphogenesis was observed in the ARC and BLA of mice intermittently administered LPS and chronically fed HFD.	71
Figure. 17 Intense GFAP immunoreactivity detected in insula of HFD-fed mice.	72
Figure. 18 Microglia morphology and iNOS expression after the treatment of anti-diabetes related drugs.	73
Figure. 19 Pro-inflammatory cytokines levels in plasma after TFP treatment within LPS.	74
Figure. 20 Dopamine D2R expression in different brain regions after HFD-feeding.	75
Figure. 21 The schematic diagram illustrates the experimental design of TFP treatment	76
Figure. 22 The bodyweight and metabolic index after TFP injection in HFD-fed mice.	77
Figure. 23 Pro-inflammatory cytokines levels in plasma after TFP treatment in HFD-fed mice.	78
Figure. 24 Microglial and astrocytic activation in ARC was diminished by TFP administration in HFD-fed mice.	79
Figure. 25 The bodyweight and metabolic index after TFP injection in HFD-fed mice.	80
Figure. 26 The bodyweight and metabolic index after simvastatin injection in HFD-fed mice.	81


                                    

1. van der Klaauw AA, Farooqi IS: The hunger genes: pathways to obesity. Cell 2015, 161(1):119-132.
2. Ghanem AM, Sen S, Philp B, Dziewulski P, Shelley OP: Body Mass Index (BMI) and mortality in patients with severe burns: is there a "tilt point" at which obesity influences outcome? Burns 2011, 37(2):208-214.
3. Katsiki N, Anagnostis P, Kotsa K, Goulis DG, Mikhailidis DP: Obesity, Metabolic Syndrome and the Risk of Microvascular Complications in Patients with Diabetes mellitus. Current Pharmaceutical Design 2019, 25(18):2051-2059.
4. Czech MP: Insulin action and resistance in obesity and type 2 diabetes. Nature Medicine 2017, 23(7):804-814.
5. Mehran AE, Templeman NM, Brigidi GS, Lim GE, Chu KY, Hu X, Botezelli JD, Asadi A, Hoffman BG, Kieffer TJ et al: Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Cell Metabolism 2012, 16(6):723-737.
6. Knight ZA, Hannan KS, Greenberg ML, Friedman JM: Hyperleptinemia Is Required for the Development of Leptin Resistance. PLoS One 2010, 5(6):e11376.
7. Mukherjee B, Hossain CM, Mondal L, Paul P, Ghosh MK: Obesity and insulin resistance: an abridged molecular correlation. Lipid Insights 2013, 6:1-11.
8. Wang H, Wen B, Cheng J, Li H: Brain Structural Differences between Normal and Obese Adults and their Links with Lack of Perseverance, Negative Urgency, and Sensation Seeking. Scientific Reports 2017, 7:40595.
9. Casquero-Veiga M, García-García D, Pascau J, Desco M, Soto-Montenegro ML: Stimulating the nucleus accumbens in obesity: A positron emission tomography study after deep brain stimulation in a rodent model. PLoS One 2018, 13(9):e0204740.
10. Ruegsegger GN, Booth FW: Running from Disease: Molecular Mechanisms Associating Dopamine and Leptin Signaling in the Brain with Physical Inactivity, Obesity, and Type 2 Diabetes. Frontiers in Endocrinology 2017, 8(109).
11. Harat M, Rudas M, Zielinski P, Birska J, Sokal P: Nucleus accumbens stimulation in pathological obesity. Neurologia i neurochirurgia polska 2016, 50(3):207-210.
12. Mestre ZL, Bischoff-Grethe A, Eichen DM, Wierenga CE, Strong D, Boutelle KN: Hippocampal atrophy and altered brain responses to pleasant tastes among obese compared with healthy weight children. International Journal of Obesity 2017, 41(10):1496-1502.
13. Cherbuin N, Sargent-Cox K, Fraser M, Sachdev P, Anstey KJ: Being overweight is associated with hippocampal atrophy: the PATH Through Life Study. International Journal of Obesity 2015, 39(10):1509-14.
14. Mueller K, Sacher J, Arelin K, Holiga S, Kratzsch J, Villringer A, Schroeter ML: Overweight and obesity are associated with neuronal injury in the human cerebellum and hippocampus in young adults: a combined MRI, serum marker and gene expression study. Translational psychiatry 2012, 2(12):e200.
15. Dietrich MO, Horvath TL: Hypothalamic control of energy balance: insights into the role of synaptic plasticity. Trends in Neurosciences 2013, 36(2):65-73.
16. Ganong WF: Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Clinical and Experimental Pharmacology and Physiology 2000, 27(5-6):422-427.
17. Kim EM, O'Hare E, Grace MK, Welch CC, Billington CJ, Levine AS: ARC POMC mRNA and PVN alpha-MSH are lower in obese relative to lean zucker rats. Brain Research 2000, 862(1-2):11-16.
18. Zheng F, Kim YJ, Chao PT, Bi S: Overexpression of neuropeptide Y in the dorsomedial hypothalamus causes hyperphagia and obesity in rats. Obesity 2013, 21(6):1086-1092.
19. Kim YJ, Bi S: Knockdown of neuropeptide Y in the dorsomedial hypothalamus reverses high-fat diet-induced obesity and impaired glucose tolerance in rats. The American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2016, 310(2):R134-142.
20. Gali Ramamoorthy T, Begum G, Harno E, White A: Developmental programming of hypothalamic neuronal circuits: Impact on energy balance control. Frontiers in neuroscience 2015, 9:126.
21. Berglund E, Vianna C, Donato J, Kim M, Chuang J-C, Lee C, Lauzon D, Lin P, Brule L, Scott M et al: Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. The Journal of clinical investigation 2012, 122 (3):1000-9.
22. Paeger L, Pippow A, Hess S, Paehler M, Klein AC, Husch A, Pouzat C, Brüning JC, Kloppenburg P: Energy imbalance alters Ca(2+) handling and excitability of POMC neurons. Elife 2017, 6:e25641.
23. Gamber KM, Huo L, Ha S, Hairston JE, Greeley S, Bjørbæk C: Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. PLoS One 2012, 7(1):e30485.
24. Moraes JC, Coope A, Morari J, Cintra DE, Roman EA, Pauli JR, Romanatto T, Carvalheira JB, Oliveira AL, Saad MJ et al: High-fat diet induces apoptosis of hypothalamic neurons. PLoS One 2009, 4(4):e5045.
25. Schmidt FM, Weschenfelder J, Sander C, Minkwitz J, Thormann J, Chittka T, Mergl R, Kirkby KC, Faßhauer M, Stumvoll M et al: Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS One 2015, 10(3):e0121971.
26. Miao H, Chen L, Hao L, Zhang X, Chen Y, Ruan Z, Liang H: Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes. Scientific Reports 2015, 5:13092.
27. Stolic M, Russell A, Hutley L, Fielding G, Hay J, MacDonald G, Whitehead J, Prins J: Glucose uptake and insulin action in human adipose tissue—influence of BMI, anatomical depot and body fat distribution. International Journal of Obesity 2002, 26(1):17-23.
28. Hwang DH, Kim JA, Lee JY: Mechanisms for the activation of Toll-like receptor 2/4 by saturated fatty acids and inhibition by docosahexaenoic acid. European Journal of Pharmacology 2016, 785:24-35.
29. Saltiel AR, Olefsky JM: Inflammatory mechanisms linking obesity and metabolic disease. Journal of Clinical Investigation 2017, 127(1):1-4.
30. Caër C, Rouault C, Le Roy T, Poitou C, Aron-Wisnewsky J, Torcivia A, Bichet JC, Clément K, Guerre-Millo M, André S: Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue. Scientific Reports 2017, 7(1):3000.
31. Ouchi N, Walsh K: Adiponectin as an anti-inflammatory factor. Clinica Chimica Acta 2007, 380(1-2):24-30.
32. Holland WL, Xia JY, Johnson JA, Sun K, Pearson MJ, Sharma AX, Quittner-Strom E, Tippetts TS, Gordillo R, Scherer PE: Inducible overexpression of adiponectin receptors highlight the roles of adiponectin-induced ceramidase signaling in lipid and glucose homeostasis. Molecular Metabolism 2017, 6(3):267-275.
33. Chen Z, Yu R, Xiong Y, Du F, Zhu S: A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease. Lipids in Health and Diseases 2017, 16(1):203.
34. Zhang B, Xu D, She L, Wang Z, Yang N, Sun R, Zhang Y, Yan C, Wei Q, Aa J et al: Silybin inhibits NLRP3 inflammasome assembly through the NAD(+)/SIRT2 pathway in mice with nonalcoholic fatty liver disease. FASEB Journal 2018, 32(2):757-767.
35. Wu H, Ballantyne CM: Skeletal muscle inflammation and insulin resistance in obesity. Journal of Clinical Investigation 2017, 127(1):43-54.
36. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR et al: Obesity is associated with hypothalamic injury in rodents and humans. Journal of Clinical Investigation 2012, 122(1):153-162.
37. Ballabh P, Braun A, Nedergaard M: The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiology of Disease 2004, 16(1):1-13.
38. Guillemot-Legris O, Muccioli GG: Obesity-Induced Neuroinflammation: Beyond the Hypothalamus. Trends in Neurosciences 2017, 40(4):237-253.
39. Basu A, Krady JK, Levison SW: Interleukin-1: A master regulator of neuroinflammation. Journal of Neuroscience Research 2004, 78(2):151-156.
40. Craft JM, Watterson DM, Hirsch E, Van Eldik LJ: Interleukin 1 receptor antagonist knockout mice show enhanced microglial activation and neuronal damage induced by intracerebroventricular infusion of human β-amyloid. Journal of Neuroinflammation 2005, 2(1):15.
41. Noronha SSR, Lima PM, Campos GSV, Chírico MTT, Abreu AR, Figueiredo AB, Silva FCS, Chianca DA, Lowry CA, De Menezes RCA: Association of high-fat diet with neuroinflammation, anxiety-like defensive behavioral responses, and altered thermoregulatory responses in male rats. Brain, Behavior, and Immunity 2019, 80:500-511.
42. Décarie-Spain L, Sharma S, Hryhorczuk C, Issa-Garcia V, Barker PA, Arbour N, Alquier T, Fulton S: Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive sucrose seeking elicited by saturated dietary fat. Molecular Metabolism 2018, 10:1-13.
43. Fernandez-Sanchez A, Madrigal-Santillan E, Bautista M, Esquivel-Soto J, Morales-Gonzalez A, Esquivel-Chirino C, Durante-Montiel I, Sanchez-Rivera G, Valadez-Vega C, Morales-Gonzalez JA: Inflammation, oxidative stress, and obesity. International Journal of Molecular Sciences 2011, 12(5):3117-3132.
44. de Mello AH, Costa AB, Engel JDG, Rezin GT: Mitochondrial dysfunction in obesity. Life Sciences 2018, 192:26-32.
45. Ferreira ST, Clarke JR, Bomfim TR, De Felice FG: Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer's disease. Alzheimer's & Dementia 2014, 10(1 Suppl):S76-83.
46. Cao C, Li L, Chen W, Zhu Y, Qi Y, Wang X, Wan X, Chen X: Deficiency of IKKepsilon inhibits inflammation and induces cardiac protection in high-fat diet-induced obesity in mice. International Journal of Molecular Medicine 2014, 34(1):244-252.
47. Shoelson SE, Lee J, Yuan M: Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. International journal of obesity and related metabolic disorders 2003, 27 Suppl 3:S49-52.
48. Li J, Tang Y, Cai D: IKKbeta/NF-kappaB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes. Nature Cell Biology 2012, 14(10):999-1012.
49. Wake H, Moorhouse AJ, Nabekura J: Functions of microglia in the central nervous system--beyond the immune response. Neuron Glia Biology 2011, 7(1):47-53.
50. Streit WJ, Walter SA, Pennell NA: Reactive microgliosis. Progress in Neurobiology 1999, 57(6):563-581.
51. Yin Z, Raj DD, Schaafsma W, van der Heijden RA, Kooistra SM, Reijne AC, Zhang X, Moser J, Brouwer N, Heeringa P et al: Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging. Frontiers in Molecular Neuroscience 2018, 11(65).
52. Valdearcos M, Robblee MM, Benjamin DI, Nomura DK, Xu AW, Koliwad SK: Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Reports 2014, 9(6):2124-2138.
53. André C, Guzman-Quevedo O, Rey C, Rémus-Borel J, Clark S, Castellanos-Jankiewicz A, Ladeveze E, Leste-Lasserre T, Nadjar A, Abrous DN et al: Inhibiting Microglia Expansion Prevents Diet-Induced Hypothalamic and Peripheral Inflammation. Diabetes 2017, 66(4):908-919.
54. Valdearcos M, Douglass JD, Robblee MM, Dorfman MD, Stifler DR, Bennett ML, Gerritse I, Fasnacht R, Barres BA, Thaler JP et al: Microglial Inflammatory Signaling Orchestrates the Hypothalamic Immune Response to Dietary Excess and Mediates Obesity Susceptibility. Cell Metabolism 2017, 26(1):185-197.
55. Kim JD, Yoon NA, Jin S, Diano S: Microglial UCP2 Mediates Inflammation and Obesity Induced by High-Fat Feeding. Cell Metabolism 2019, 30(5):952-962.e5..
56. Buckman LB, Ellacott KLJ: The contribution of hypothalamic macroglia to the regulation of energy homeostasis. Frontiers in Systems Neuroscience 2014, 8(212).
57. Varvel NH, Grathwohl SA, Baumann F, Liebig C, Bosch A, Brawek B, Thal DR, Charo IF, Heppner FL, Aguzzi A et al: Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells. Proceedings of the National Academy of Sciences 2012, 109(44): 18150-5.
58. Baufeld C, Osterloh A, Prokop S, Miller KR, Heppner FL: High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia. Acta neuropathologica 2016, 132(3):361-375.
59. Douglass JD, Dorfman MD, Fasnacht R, Shaffer LD, Thaler JP: Astrocyte IKKβ/NF-κB signaling is required for diet-induced obesity and hypothalamic inflammation. Molecular Metabolism 2017, 6(4):366-373.
60. Sofroniew MV, Vinters HV: Astrocytes: biology and pathology. Acta neuropathologica 2010, 119(1):7-35.
61. Pekny M, Pekna M: Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits. Physiological Reviews 2014, 94(4):1077-1098.
62. Berkseth KE, Guyenet SJ, Melhorn SJ, Lee D, Thaler JP, Schur EA, Schwartz MW: Hypothalamic gliosis associated with high-fat diet feeding is reversible in mice: a combined immunohistochemical and magnetic resonance imaging study. Endocrinology 2014, 155(8):2858-2867.
63. Bouyakdan K, Martin H, Lienard F, Budry L, Taib B, Rodaros D, Chretien C, Biron E, Husson Z, Cota D et al: The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system. Journal of Clinical Investigation 2019, 129(6):2417-2430.
64. Bradl M, Lassmann H: Oligodendrocytes: biology and pathology. Acta Neuropathologica 2010, 119(1):37-53.
65. Toyama K, Koibuchi N, Hasegawa Y, Uekawa K, Yasuda O, Sueta D, Nakagawa T, Ma M, Kusaka H, Lin B et al: ASK1 is involved in cognitive impairment caused by long-term high-fat diet feeding in mice. Scientific Reports 2015, 5:10844.
66. Graham LC, Grabowska WA, Chun Y, Risacher SL, Philip VM, Saykin AJ, Sukoff Rizzo SJ, Howell GR: Exercise prevents obesity-induced cognitive decline and white matter damage in mice. Neurobiology of Aging 2019, 80:154-172.
67. Xiao G, Burguet J, Kawaguchi R, Havton LA, Hinman JD: Obesity restricts oligodendrocyte maturation and impedes repair after white matter stroke. bioRxiv 2018:283184.
68. Lin W, Harding HP, Ron D, Popko B: Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-γ. Journal of Cell Biology 2005, 169(4):603-612.
69. Martin-Jiménez CA, Gaitán-Vaca DM, Echeverria V, González J, Barreto GE: Relationship Between Obesity, Alzheimer’s Disease, and Parkinson’s Disease: an Astrocentric View. Molecular Neurobiology 2017, 54(9):7096-7115.
70. Alford S, Patel D, Perakakis N, Mantzoros CS: Obesity as a risk factor for Alzheimer's disease: weighing the evidence. Obesity Reviews 2018, 19(2):269-280.
71. Molteni R, Barnard RJ, Ying Z, Roberts CK, Gomez-Pinilla F: A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 2002, 112(4):803-814.
72. Rivera P, Perez-Martin M, Pavon FJ, Serrano A, Crespillo A, Cifuentes M, Lopez-Avalos MD, Grondona JM, Vida M, Fernandez-Llebrez P et al: Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus. PLoS One 2013, 8(5):e64750.
73. Theriault P, ElAli A, Rivest S: High fat diet exacerbates Alzheimer's disease-related pathology in APPswe/PS1 mice. Oncotarget 2016, 7(42):67808-67827.
74. Petrov D, Pedros I, Artiach G, Sureda FX, Barroso E, Pallas M, Casadesus G, Beas-Zarate C, Carro E, Ferrer I et al: High-fat diet-induced deregulation of hippocampal insulin signaling and mitochondrial homeostasis deficiences contribute to Alzheimer disease pathology in rodents. Biochimica et Biophysica Acta 2015, 1852(9):1687-1699.
75. Naderali EK, Ratcliffe SH, Dale MC: Obesity and Alzheimer's disease: a link between body weight and cognitive function in old age. American Journal of Alzheimer's Disease and other Dementias 2009, 24(6):445-449.
76. Wang W-Y, Tan M-S, Yu J-T, Tan L: Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Annals of Translational Medicine 2015, 3(10):136.
77. Domingues C, da Cruz E Silva OAB, Henriques AG: Impact of Cytokines and Chemokines on Alzheimer's Disease Neuropathological Hallmarks. Current Alzheimer research 2017, 14(8):870-882.
78. Alasmari F, Alshammari MA, Alasmari AF, Alanazi WA, Alhazzani K: Neuroinflammatory Cytokines Induce Amyloid Beta Neurotoxicity through Modulating Amyloid Precursor Protein Levels/Metabolism. BioMed Research International 2018, 2018:1-8.
79. Lukens JR, Gross JM, Kanneganti T-D: IL-1 family cytokines trigger sterile inflammatory disease. Frontiers in immunology 2012, 3:315.
80. Xiong Z, Thangavel R, Kempuraj D, Yang E, Zaheer S, Zaheer A: Alzheimer's disease: evidence for the expression of interleukin-33 and its receptor ST2 in the brain. Journal of Alzheimers Disease 2014, 40(2):297-308.
81. Allan D, Fairlie-Clarke KJ, Elliott C, Schuh C, Barnett SC, Lassmann H, Linnington C, Jiang H-R: Role of IL-33 and ST2 signalling pathway in multiple sclerosis: expression by oligodendrocytes and inhibition of myelination in central nervous system. Acta Neuropathologica Communications 2016, 4(1):75.
82. Carlock C, Wu J, Shim J, Moreno-Gonzalez I, Pitcher MR, Hicks J, Suzuki A, Iwata J, Quevado J, Lou Y: Interleukin33 deficiency causes tau abnormality and neurodegeneration with Alzheimer-like symptoms in aged mice. Translational Psychiatry 2017, 7(7):e1164.
83. Fu AKY, Hung K-W, Yuen MYF, Zhou X, Mak DSY, Chan ICW, Cheung TH, Zhang B, Fu W-Y, Liew FY et al: IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline. Proceedings of the National Academy of Sciences 2016, 113(19):e2705-e2713.
84. Chen J, Guan Z, Wang L, Song G, Ma B, Wang Y: Meta-analysis: overweight, obesity, and Parkinson's disease. International Journal of Endocrinology 2014, 2014:1-7.
85. Chen H, Zhang SM, Schwarzschild MA, Hernan MA, Willett WC, Ascherio A: Obesity and the risk of Parkinson's disease. American Journal of Epidemiology 2004, 159(6):547-555.
86. Ferrari CC, Pott Godoy MC, Tarelli R, Chertoff M, Depino AM, Pitossi FJ: Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1beta in the substantia nigra. Neurobiology of Disease 2006, 24(1):183-193.
87. Tovote P, Fadok JP, Lüthi A: Neuronal circuits for fear and anxiety. Nature Reviews Neuroscience 2015, 16:317-31.
88. Brooks SJ, Stein DJ: A systematic review of the neural bases of psychotherapy for anxiety and related disorders. Dialogues in Clinical Neuroscience 2015, 17(3):261-279.
89. Castro DC, Cole SL, Berridge KC: Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry. Frontiers in Systems Neuroscience 2015, 9(90).
90. Scofield MD, Heinsbroek JA, Gipson CD, Kupchik YM, Spencer S, Smith ACW, Roberts-Wolfe D, Kalivas PW: The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis. Pharmacological Reviews 2016, 68(3):816-871.
91. Russo SJ, Nestler EJ: The brain reward circuitry in mood disorders. Nature Reviews Neuroscience 2013, 14:609-25.
92. Schindler S, Geyer S, Strauss M, Anwander A, Hegerl U, Turner R, Schonknecht P: Structural studies of the hypothalamus and its nuclei in mood disorders. Psychiatric Research 2012, 201(1):1-9.
93. Woodworth CH: Attack elicited in rats by electrical stimulation of the lateral hypothalamus. Physiology & Behavior 1971, 6(4):345-353.
94. Smith SM, Vale WW: The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in Clinical Neuroscience 2006, 8(4):383-395.
95. Maric NP, Adzic M: Pharmacological modulation of HPA axis in depression - new avenues for potential therapeutic benefits. Psychiatr Danub 2013, 25(3):299-305.
96. Claes SJ: Corticotropin-releasing hormone (CRH) in psychiatry: from stress to psychopathology. Ann Med 2004, 36(1):50-61.
97. Okamoto S, Sato T, Tateyama M, Kageyama H, Maejima Y, Nakata M, Hirako S, Matsuo T, Kyaw S, Shiuchi T et al: Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat. Cell Reports 2018, 22(3):706-721.
98. Felger JC: Imaging the Role of Inflammation in Mood and Anxiety-related Disorders. Current Neuropharmacology 2018, 16(5):533-558.
99. Ferrari P, Parisi MM, Colombo R, Becker M, Fries G, Ascoli BM, Géa LP, Anna MK, Kapczinski F, Klamt F et al: Depression and Mania Induce Pro-inflammatory Activation of Macrophages Following Application of Serum from Individuals with Bipolar Disorder. Clinical Psychopharmacology and Neuroscience 2018, 16(1):103-108.
100. Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T: Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond. Neuropsychopharmacology 2017, 42(1):254-270.
101. Steiner J, Bielau H, Brisch R, Danos P, Ullrich O, Mawrin C, Bernstein HG, Bogerts B: Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. Journal of Psychiatric 2008, 42(2):151-157.
102. Rao JS, Harry GJ, Rapoport SI, Kim HW: Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients. Molecular Psychiatry 2009, 15:384-92.
103. Feresten AH, Barakauskas V, Ypsilanti A, Barr AM, Beasley CL: Increased expression of glial fibrillary acidic protein in prefrontal cortex in psychotic illness. Schizophrenia Research 2013, 150(1):252-257.
104. Chu Qi C, zhu Ma X, Chao Chen H, Jun Wang Q, Ping Gao L, Yin J, Hong Jing Y: Microglial Activation in the Ventral Hippocampus Induced by Acute Social Defeat is Associated with Amygdala Activity. Neuropsychiatry 2018, 08.
105. Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T: Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond. Neuropsychopharmacology 2016, 42:254-270.
106. Peruga I, Hartwig S, Thone J, Hovemann B, Gold R, Juckel G, Linker RA: Inflammation modulates anxiety in an animal model of multiple sclerosis. Behavioural Brain Research 2011, 220(1):20-29.
107. Salim S, Asghar M, Taneja M, Hovatta I, Chugh G, Vollert C, Vu A: Potential contribution of oxidative stress and inflammation to anxiety and hypertension. Brain Research 2011, 1404:63-71.
108. Young JJ, Bruno D, Pomara N: A review of the relationship between proinflammatory cytokines and major depressive disorder. Journal of Affective Disorders 2014, 169:15-20.
109. Edgar N, Sibille E: A putative functional role for oligodendrocytes in mood regulation. Translational psychiatry 2012, 2(5):e109.
110. Hao S, Dey A, Yu X, Stranahan AM: Dietary obesity reversibly induces synaptic stripping by microglia and impairs hippocampal plasticity. Brain, Behavior, and Immunity 2016, 51:230-239.
111. Liu Y, Zhou L-J, Wang J, Li D, Ren W-J, Peng J, Wei X, Xu T, Xin W-J, Pang R-P et al: TNF-α Differentially Regulates Synaptic Plasticity in the Hippocampus and Spinal Cord by Microglia-Dependent Mechanisms after Peripheral Nerve Injury. Journal of neuroscience 2017, 37(4):871-881.
112. Copeland S, Warren HS, Lowry SF, Calvano SE, Remick D: Acute Inflammatory Response to Endotoxin in Mice and Humans. Clinical and Diagnostic Laboratory Immunology 2005, 12(1):60-67.
113. O'Connor JC, Lawson MA, André C, Moreau M, Lestage J, Castanon N, Kelley KW, Dantzer R: Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Molecular Psychiatry 2009, 14(5):511-522.
114. Zhao J, Bi W, Xiao S, Lan X, Cheng X, Zhang J, Lu D, Wei W, Wang Y, Li H et al: Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Scientific Reports 2019, 9(1):5790.
115. Sulakhiya K, Keshavlal GP, Bezbaruah BB, Dwivedi S, Gurjar SS, Munde N, Jangra A, Lahkar M, Gogoi R: Lipopolysaccharide induced anxiety- and depressive-like behaviour in mice are prevented by chronic pre-treatment of esculetin. Neuroscience Letters 2016, 611:106-111.
116. Vogelzangs N, de Jonge P, Smit JH, Bahn S, Penninx BW: Cytokine production capacity in depression and anxiety. Translational Psychiatry 2016, 6:e825.
117. Cordeiro RC, Chaves Filho AJM, Gomes NS, Tomaz VdS, Medeiros CD, Queiroz AIdG, Maes M, Macedo DS, Carvalho AF: Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors. Frontiers in Psychiatry 2019, 10(125).
118. Kesebir S: Epigenetics of Metabolic Syndrome as a Mood Disorder. J Clin Med Res 2018, 10(6):453-460.
119. Mansur RB, Brietzke E, McIntyre RS: Is there a “metabolic-mood syndrome”? A review of the relationship between obesity and mood disorders. Neuroscience & Biobehavioral Reviews 2015, 52:89-104.
120. Martinac M, Pehar D, Karlovic D, Babic D, Marcinko D, Jakovljevic M: Metabolic syndrome, activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in depressive disorder. Acta Clinica Croatica 2014, 53(1):55-71.
121. McIntyre RS, Alsuwaidan M, Goldstein BI, Taylor VH, Schaffer A, Beaulieu S, Kemp DE: The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid metabolic disorders. Annals of Clinical Psychiatry 2012, 24(1):69-81.
122. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG: Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Archives Of General Psychiatr 2010, 67(3):220-229.
123. Simon GE, Ludman EJ, Linde JA, Operskalski BH, Ichikawa L, Rohde P, Finch EA, Jeffery RW: Association between obesity and depression in middle-aged women. General hospital psychiatry 2008, 30(1):32-39.
124. Kubzansky LD, Gilthorpe MS, Goodman E: A prospective study of psychological distress and weight status in adolescents/young adults. Ann Behav Med 2012, 43(2):219-228.
125. Kocakaya H, Batmaz S, Demir O, Songur E, Celikbas Z: Metabolic syndrome in bipolar disorder: prevalence, demographics and clinical correlates in individuals with bipolar I, bipolar II, and healthy controls. Archives of Clinical Psychiatry 2018, 45:143-149.
126. Silarova B, Giltay EJ, Van Reedt Dortland A, Van Rossum EF, Hoencamp E, Penninx BW, Spijker AT: Metabolic syndrome in patients with bipolar disorder: comparison with major depressive disorder and non-psychiatric controls. Journal of Psychosomatic Research 2015, 78(4):391-398.
127. Cope EC, LaMarca EA, Monari PK, Olson LB, Martinez S, Zych AD, Katchur NJ, Gould E: Microglia Play an Active Role in Obesity-Associated Cognitive Decline. The Journal of Neuroscience 2018, 38(41):8889-8904.
128. Vagena E, Ryu JK, Baeza-Raja B, Walsh NM, Syme C, Day JP, Houslay MD, Baillie GS: A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling. Translational Psychiatry 2019, 9(1):141.
129. Toups MSP, Myers AK, Wisniewski SR, Kurian B, Morris DW, Rush AJ, Fava M, Trivedi MH: Relationship between obesity and depression: characteristics and treatment outcomes with antidepressant medication. Psychosomatic medicine 2013, 75(9):863-872.
130. Martinac M, Babic D, Bevanda M, Vasilj I, Glibo DB, Karlovic D, Jakovljevic M: Activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in major depressive disorder with or without metabolic syndrome. Psychiatr Danub 2017, 29(1):39-50.
131. Davy Vancampfort, Ph.D. ,, Kristof Vansteelandt, Ph.D. ,, Christoph U. Correll, M.D. ,, Alex J. Mitchell, M.D. ,, Amber De Herdt, M.Sc. ,, Pascal Sienaert, M.D., Ph.D. ,, Michel Probst, Ph.D. , and, Marc De Hert, M.D., Ph.D.: Metabolic Syndrome and Metabolic Abnormalities in Bipolar Disorder: A Meta-Analysis of Prevalence Rates and Moderators. American Journal of Psychiatry 2013, 170(3):265-274.
132. Gautam S, Meena PS: Drug-emergent metabolic syndrome in patients with schizophrenia receiving atypical (second-generation) antipsychotics. Indian J Psychiatry 2011, 53(2):128-133.
133. Tschoner A, Engl J, Rettenbacher M, Edlinger M, Kaser S, Tatarczyk T, Effenberger M, Patsch JR, Fleischhacker WW, Ebenbichler CF: Effects of six second generation antipsychotics on body weight and metabolism - risk assessment and results from a prospective study. Pharmacopsychiatry 2009, 42(1):29-34.
134. Roix JJ, DeCrescenzo GA, Cheung PH, Ciallella JR, Sulpice T, Saha S, Halse R: Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion. Diabetes, Obesity and Metabolism 2012, 14(4):329-334.
135. Correll CU, Lencz T, Malhotra AK: Antipsychotic drugs and obesity. Trends in molecular medicine 2011, 17(2):97-107.
136. Sicras-Mainar A, Navarro-Artieda R, Rejas-Gutiérrez J, Blanca-Tamayo M: Relationship between obesity and antipsychotic drug use in the adult population: a longitudinal, retrospective claim database study in Primary Care settings. Neuropsychiatric disease and treatment 2008, 4(1):219-226.
137. Gadani SP, Walsh JT, Smirnov I, Zheng J, Kipnis J: The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury. Neuron 2015, 85(4):703-709.
138. Huang H-T, Tsai S-F, Wu H-T, Huang H-Y, Hsieh H-H, Kuo Y-M, Chen P-S, Yang C-S, Tzeng S-F: Chronic exposure to high fat diet triggers myelin disruption and interleukin-33 upregulation in hypothalamus. BMC Neuroscience 2019, 20(1):33.
139. Holder MK, Blaustein JD: Developmental time course and effects of immunostressors that alter hormone-responsive behavior on microglia in the peripubertal and adult female mouse brain. PLoS One 2017, 12(2):e0171381.
140. Yang TT, Lin C, Hsu CT, Wang TF, Ke FY, Kuo YM: Differential distribution and activation of microglia in the brain of male C57BL/6J mice. Brain Structure & Function 2013, 218(4):1051-1060.
141. Boksem MA, Tops M: Mental fatigue: costs and benefits. Brain Research Reviews 2008, 59(1):125-139.
142. Marques LDO, Soares B, Silva de Lima M: Trifluoperazine for schizophrenia. Cochrane Database of Systematic Reviews 2004(1): CD003545.
143. Duan Y, Zeng L, Zheng C, Song B, Li F, Kong X, Xu K: Inflammatory Links Between High Fat Diets and Diseases. Frontiers in Immunology 2018, 9(2649).
144. Nakashima T, Hori T, Mori T, Kuriyama K, Mizuno K: Recombinant human interleukin-1 beta alters the activity of preoptic thermosensitive neurons in vitro. Brain Research Bulletin 1989, 23(3):209-213.
145. Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS: Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proceedings of the National Academy of Sciences of the United States of America 2010, 107(6):2669-2674.
146. Burmeister AR, Marriott I: The Interleukin-10 Family of Cytokines and Their Role in the CNS. Frontiers in Cellular Neuroscience 2018, 12:458.
147. Dubový P, Klusáková I, Hradilová-Svíženská I, Joukal M, Boadas-Vaello P: Activation of Astrocytes and Microglial Cells and CCL2/CCR2 Upregulation in the Dorsolateral and Ventrolateral Nuclei of Periaqueductal Gray and Rostral Ventromedial Medulla Following Different Types of Sciatic Nerve Injury. Frontiers in Cellular Neuroscience 2018, 12:40.
148. de Aquino CC, Leitão RA, Oliveira Alves LA, Coelho-Santos V, Guerrant RL, Ribeiro CF, Malva JO, Silva AP, Oriá RB: Effect of Hypoproteic and High-Fat Diets on Hippocampal Blood-Brain Barrier Permeability and Oxidative Stress. Frontiers in Nutrition 2019, 5(131).
149. Molofsky AB, Savage AK, Locksley RM: Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation. Immunity 2015, 42(6):1005-1019.
150. Fairlie-Clarke K, Barbour M, Wilson C, Hridi SU, Allan D, Jiang H-R: Expression and Function of IL-33/ST2 Axis in the Central Nervous System Under Normal and Diseased Conditions. Frontiers in Immunology 2018, 9(2596).
151. Yang Y, Liu H, Zhang H, Ye Q, Wang J, Yang B, Mao L, Zhu W, Leak RK, Xiao B et al: ST2/IL-33-Dependent Microglial Response Limits Acute Ischemic Brain Injury. Journal of Neuroscience 2017, 37(18):4692-4704.
152. Natarajan C, Yao SY, Sriram S: TLR3 Agonist Poly-IC Induces IL-33 and Promotes Myelin Repair. PLoS One 2016, 11(3):e0152163.
153. Sung HY, Chen WY, Huang HT, Wang CY, Chang SB, Tzeng SF: Down-regulation of interleukin-33 expression in oligodendrocyte precursor cells impairs oligodendrocyte lineage progression. Journal of Neurochemistry 2019, 150(6):691-708.
154. Fattori V, Borghi SM, Verri WA: IL-33/ST2 signaling boosts inflammation and pain. Proceedings of the National Academy of Sciences 2017, 114(47):e10034-e10035.
155. Zarpelon AC, Rodrigues FC, Lopes AH, Souza GR, Carvalho TT, Pinto LG, Xu D, Ferreira SH, Alves-Filho JC, McInnes IB et al: Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain. The FASEB Journal 2016, 30(1):54-65.
156. Mahmutovic Persson I, Menzel M, Ramu S, Cerps S, Akbarshahi H, Uller L: IL-1β mediates lung neutrophilia and IL-33 expression in a mouse model of viral-induced asthma exacerbation. Respiratory Research 2018, 19(1):16.
157. Zaiss MM, Maslowski KM, Mosconi I, Guenat N, Marsland BJ, Harris NL: IL-1β Suppresses Innate IL-25 and IL-33 Production and Maintains Helminth Chronicity. PLoS Pathogens 2013, 9(8):e1003531.
158. Nordgreen J, Munsterhjelm C, Aae F, Popova A, Boysen P, Ranheim B, Heinonen M, Raszplewicz J, Piepponen P, Lervik A et al: The effect of lipopolysaccharide (LPS) on inflammatory markers in blood and brain and on behavior in individually-housed pigs. Physiology & Behavior 2018, 195:98-111.
159. Quan N, Whiteside M, Herkenham M: Time course and localization patterns of interleukin-1beta messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide. Neuroscience 1998, 83(1):281-293.
160. Quan N, Stern EL, Whiteside MB, Herkenham M: Induction of pro-inflammatory cytokine mRNAs in the brain after peripheral injection of subseptic doses of lipopolysaccharide in the rat. Journal of Neuroimmunology 1999, 93(1-2):72-80.
161. Chen Z, Jalabi W, Shpargel KB, Farabaugh KT, Dutta R, Yin X, Kidd GJ, Bergmann CC, Stohlman SA, Trapp BD: Lipopolysaccharide-induced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4. Journal of neuroscience 2012, 32(34):11706-11715.
162. Wendeln AC, Degenhardt K, Kaurani L, Gertig M, Ulas T, Jain G, Wagner J, Hasler LM, Wild K, Skodras A et al: Innate immune memory in the brain shapes neurological disease hallmarks. Nature 2018, 556(7701):332-338.
163. Biswas SK, Lopez-Collazo E: Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends in immunology 2009, 30(10):475-487.
164. Becerra-Calixto A, Cardona-Gómez GP: The Role of Astrocytes in Neuroprotection after Brain Stroke: Potential in Cell Therapy. Frontiers in Molecular Neuroscience 2017, 10(88).
165. Buckman LB, Thompson MM, Lippert RN, Blackwell TS, Yull FE, Ellacott KLJ: Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice. Molecular Metabolism 2014, 4(1):58-63.
166. Huck JHJ, Freyer D, Böttcher C, Mladinov M, Muselmann-Genschow C, Thielke M, Gladow N, Bloomquist D, Mergenthaler P, Priller J: De novo expression of dopamine D2 receptors on microglia after stroke. J Cereb Blood Flow Metab 2015, 35(11):1804-1811.
167. Mahmoodi M, Hadad MK, Shamsizadeh A, Azarang A, Rayeni RA: Effect of trifluoperazine on carrageenan-induced acute inflammation in intact and adrenalectomized rats. International Journal of Physiology, Pathophysiology and Pharmacology 2009, 1(2):150-153.
168. Khaksari M, Mahmoudi M, Asadi Karam GR, Ferdosi F, Shariati M: The Effect of Trifluoperazine on Increased Vascular Permeability in an Experimental Model of Chronic Diabetic Rat. Physiology and Pharmacology 2005, 9(1):47-55.
169. Pellow S, File SE: Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacology Biochemistry & Behavior 1986, 24(3):525-529.
170. Yang Y, Wang J-Z: From Structure to Behavior in Basolateral Amygdala-Hippocampus Circuits. Frontiers in Neural Circuits 2017, 11:86-86.
171. Stein DJ, Vasconcelos MF, Albrechet-Souza L, Ceresér KMM, de Almeida RMM: Microglial Over-Activation by Social Defeat Stress Contributes to Anxiety- and Depressive-Like Behaviors. Frontiers in Behavioral Neuroscience 2017, 11:207.
172. Tynan RJ, Naicker S, Hinwood M, Nalivaiko E, Buller KM, Pow DV, Day TA, Walker FR: Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions. Brain, Behavior, and Immunity 2010, 24(7):1058-1068.

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