儘管短期壓力可以使我們提高警覺遠離危險，但慢性壓力不僅會導致身體各個部位產生疾病，還會增加產生精神和情緒問題的風險，例如憂鬱症，而嚴重的憂鬱症最可怕的地方是可能導致病患產生自殺的念頭，此外，慢性壓力也會導致認知功能障礙，以及增加罹患失智症和阿茲海默氏症的風險，甚至會導致神經退化，而這可能是造成大腦衰老的原因。記憶缺陷是大腦衰老最主要的特徵，也是阿茲海默氏症最常見的症狀。近期有研究指出細胞衰老是老化的標誌，而造成細胞衰老的原因包括DNA損傷，發炎和壓力，然而細胞衰老對於壓力誘導產生的記憶受損的作用仍不清楚，因此本篇研究意旨於探討細胞衰老是否能調節慢性壓力誘導產生的記憶缺損。我們使用慢性不可預測的壓力模型（CUS）來模擬C57BL / 6小鼠處於充滿壓力的生活狀況，結果中我們發現經過CUS的小鼠產生認知障礙和細胞衰老的現象，為了進一步確認細胞衰老與認知功能障礙之間的關係，我們使用抗衰老藥來以清除衰老的細胞，發現在清除衰老細胞後可以挽救CUS誘導產生的認知障礙。除此以外，先前的研究指出腦衰反應調節蛋白5（CRMP5）是腦衰反應調節蛋白家族的一員，其表現在海馬迴中，並與精神障礙以及神經退行性疾病有關聯，但是CRMP5在壓力誘導產生的記憶缺陷中的作用目前仍不清楚。因此本篇研究的另一個目的為探討CRMP5是否能調節慢性壓力誘導產生的記憶缺陷。根據結果顯示經歷過CUS的小鼠其海馬迴中CRMPs的表現量會增加，尤其是CRMP2和CRMP5，但只有CRMP5的表現量高低與認知障礙的嚴重程度呈負相關性，為了進一步確認CRMP5與記憶障礙之間的關聯性，我們將Dpysl5（CRMP5）shRNA或Dpysl5 cDNA注射進小鼠的海馬迴中，結果發現降低CRMP5表現量後可以挽救CUS誘導的認知障礙，相反的，正常小鼠在增加CRMP5表現量後給予不超過閾值的微量壓力則會加劇記憶力受損，此外我們發現與Dpysl5-GRE結合的磷酸化糖皮質激素受體 (pGR）表現量顯著增加，還發現了調控CRMP5的表現量會影響經歷過CUS的小鼠其海馬迴中的神經發育以及發炎因子的分泌。綜合以上所有發現表明了細胞衰老和CRMP5可能是慢性壓力誘導產生記憶障礙的新治療靶標。

Although acute stress can make us alert to stay away from danger, chronic stress not only leads to diseases of the body but also increases the risk of mental and emotional problems, such as depression. The most terrible thing is that severe depression can lead to suicide. In addition, chronic stress can cause cognitive impairment, has a higher risk of dementia and Alzheimer's disease and even leads to neuronal degeneration, which may be the cause of brain aging. Memory impairment is the most major characteristic of brain aging, which is a common symptom in Alzheimer's disease. Recent studies have indicated that cellular senescence is a hallmark of aging, which is caused by DNA damage, inflammation, and stress. However, the role of cellular senescence in stress-induced memory decline is still not clear. Thus, this study aimed to examine whether cellular senescence would modulate chronic stress-induced memory impairments. We used chronic unpredictable stress (CUS) to mimic stressful life situations in C57BL/6 mice. In this study, CUS-treated mice exhibited cognitive impairments and cellular senescence. To further confirm the association between cellular senescence and cognitive impairments, we used senolytic drugs to clear senescent cells. The data showed that the clearance of senescent cells rescued CUS-induced cognitive impairments. In addition, previous studies suggest that the collapsin response mediator protein 5 (CRMP5) is a member of the CRMP family, which expresses in the hippocampus and is involved in mental disorders and neurodegenerative diseases. However, the role of CRMP5 in stress-induced memory deficits is still not clear. Thus, another aim of our study is to examine whether CRMP5 would modulate the chronic stress-induced memory impairments. The data showed that CUS-treated mice increased hippocampal CRMPs levels, especially CRMP2 and CRMP5 expressions, but only CRMP5 levels had a negative correlation with the severity of cognitive impairments. To further confirm the association between CRMP5 expressions and memory impairments, we injected Dpysl5 (CRMP5) shRNA or Dpysl5 cDNA into mouse hippocampi. The data showed that knockdown of CRMP5 levels rescued CUS-induced cognitive impairment, whereas increased CRMP5 levels in control mice exacerbated memory decline after subthreshold stress treatment. In addition, we found that phosphorylation of the glucocorticoid receptors (pGR) binding to the Dpysl5-GRE was significantly increased. We also found that the regulation of CRMP5 affects hippocampal neurogenesis and secretion of inflammatory factors in CUS-treated mice. Taken together, our study indicated that cellular senescence and CRMP5 may be new therapeutic targets for chronic stress-induced memory impairments.

Abelaira, H. M., G. Z. Reus, and J. Quevedo. 2013. 'Animal models as tools to study the pathophysiology of depression', Braz J Psychiatry, 35 Suppl 2: S112-20.
Abraham, Y., B. Gerrits, M. G. Ludwig, M. Rebhan, and C. Gubser Keller. 2017. 'Exploring Glucocorticoid Receptor Agonists Mechanism of Action Through Mass Cytometry and Radial Visualizations', Cytometry B Clin Cytom, 92: 42-56.
Bachevalier, J. 2019. 'Nonhuman primate models of hippocampal development and dysfunction', Proc Natl Acad Sci U S A.
Ben-Yakov, A., and Y. Dudai. 2011. 'Constructing realistic engrams: poststimulus activity of hippocampus and dorsal striatum predicts subsequent episodic memory', J Neurosci, 31: 9032-42.
Bergmann, T. O., M. Molle, J. Diedrichs, J. Born, and H. R. Siebner. 2012. 'Sleep spindle-related reactivation of category-specific cortical regions after learning face-scene associations', Neuroimage, 59: 2733-42.
Bettio, L. E. B., L. Rajendran, and J. Gil-Mohapel. 2017. 'The effects of aging in the hippocampus and cognitive decline', Neurosci Biobehav Rev, 79: 66-86.
Bilal, N., N. Suhail, S. Hasan, G. M. Ashraf, S. Fatima, H. Y. Khan, M. S. Alharbi, A. Alexiou, and N. Banu. 2017. 'Exacerbation of N-nitrosodiethylamine Induced Hepatotoxicity and DNA Damage in Mice Exposed to Chronic Unpredictable Stress', Front Pharmacol, 8: 360.
Bremner, J. D. 2006. 'Traumatic stress: effects on the brain', Dialogues Clin Neurosci, 8: 445-61.
Brot, S., V. Rogemond, V. Perrot, N. Chounlamountri, C. Auger, J. Honnorat, and M. Moradi-Ameli. 2010. 'CRMP5 interacts with tubulin to inhibit neurite outgrowth, thereby modulating the function of CRMP2', J Neurosci, 30: 10639-54.
Bruel-Jungerman, E., S. Davis, C. Rampon, and S. Laroche. 2006. 'Long-term potentiation enhances neurogenesis in the adult dentate gyrus', J Neurosci, 26: 5888-93.
Burke, S. N., and C. A. Barnes. 2006. 'Neural plasticity in the ageing brain', Nat Rev Neurosci, 7: 30-40.
Childs, B. G., M. Gluscevic, D. J. Baker, R. M. Laberge, D. Marquess, J. Dananberg, and J. M. van Deursen. 2017. 'Senescent cells: an emerging target for diseases of ageing', Nat Rev Drug Discov, 16: 718-35.
Coppe, J. P., C. K. Patil, F. Rodier, Y. Sun, D. P. Munoz, J. Goldstein, P. S. Nelson, P. Y. Desprez, and J. Campisi. 2008. 'Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor', PLoS Biol, 6: 2853-68.
Cotter, M. A., S. R. Florell, S. A. Leachman, and D. Grossman. 2007. 'Absence of senescence-associated beta-galactosidase activity in human melanocytic nevi in vivo', J Invest Dermatol, 127: 2469-71.
de Magalhaes, J. P., and J. F. Passos. 2018. 'Stress, cell senescence and organismal ageing', Mech Ageing Dev, 170: 2-9.
De Sio, S., G. Buomprisco, R. Perri, G. Bruno, N. Mucci, H. A. Nieto, E. Trovato Battagliola, and F. Cedrone. 2020. 'Work-related stress risk and preventive measures of mental disorders in the medical environment: an umbrella review', Eur Rev Med Pharmacol Sci, 24: 821-30.
Demyanenko, G. P., A. Y. Tsai, and P. F. Maness. 1999. 'Abnormalities in neuronal process extension, hippocampal development, and the ventricular system of L1 knockout mice', J Neurosci, 19: 4907-20.
Deng, W., J. B. Aimone, and F. H. Gage. 2010. 'New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?', Nat Rev Neurosci, 11: 339-50.
Dhabhar, F. S. 2014. 'Effects of stress on immune function: the good, the bad, and the beautiful', Immunol Res, 58: 193-210.
Diaconu, C., L. Tartau, and C. E. Lupusoru. 2011. '[The influence of stress factors on liver function and lipid metabolism in an animal model of arterial hypertension]', Rev Med Chir Soc Med Nat Iasi, 115: 871-5.
Dickstein, D. L., C. M. Weaver, J. I. Luebke, and P. R. Hof. 2013. 'Dendritic spine changes associated with normal aging', Neuroscience, 251: 21-32.
Dimri, G. P., X. Lee, G. Basile, M. Acosta, G. Scott, C. Roskelley, E. E. Medrano, M. Linskens, I. Rubelj, O. Pereira-Smith, and et al. 1995. 'A biomarker that identifies senescent human cells in culture and in aging skin in vivo', Proc Natl Acad Sci U S A, 92: 9363-7.
Fukata, Y., T. J. Itoh, T. Kimura, C. Menager, T. Nishimura, T. Shiromizu, H. Watanabe, N. Inagaki, A. Iwamatsu, H. Hotani, and K. Kaibuchi. 2002. 'CRMP-2 binds to tubulin heterodimers to promote microtubule assembly', Nat Cell Biol, 4: 583-91.
Ghosh, S., T. R. Laxmi, and S. Chattarji. 2013. 'Functional connectivity from the amygdala to the hippocampus grows stronger after stress', J Neurosci, 33: 7234-44.
Goshima, Y., F. Nakamura, P. Strittmatter, and S. M. Strittmatter. 1995. 'Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33', Nature, 376: 509-14.
Hasan, S., N. Suhail, N. Bilal, G. M. Ashraf, S. K. Zaidi, S. AlNohair, and N. Banu. 2016. 'Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway', Tumour Biol, 37: 5999-6006.
Hewitt, G., D. Jurk, F. D. Marques, C. Correia-Melo, T. Hardy, A. Gackowska, R. Anderson, M. Taschuk, J. Mann, and J. F. Passos. 2012. 'Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence', Nat Commun, 3: 708.
Hotta, A., R. Inatome, J. Yuasa-Kawada, Q. Qin, H. Yamamura, and S. Yanagi. 2005. 'Critical role of collapsin response mediator protein-associated molecule CRAM for filopodia and growth cone development in neurons', Mol Biol Cell, 16: 32-9.
Immordino-Yang, M. H., and V. Singh. 2013. 'Hippocampal contributions to the processing of social emotions', Hum Brain Mapp, 34: 945-55.
Inatome, R., T. Tsujimura, T. Hitomi, N. Mitsui, P. Hermann, S. Kuroda, H. Yamamura, and S. Yanagi. 2000. 'Identification of CRAM, a novel unc-33 gene family protein that associates with CRMP3 and protein-tyrosine kinase(s) in the developing rat brain', J Biol Chem, 275: 27291-302.
John, A., U. Patel, J. Rusted, M. Richards, and D. Gaysina. 2019. 'Affective problems and decline in cognitive state in older adults: a systematic review and meta-analysis', Psychol Med, 49: 353-65.
Jurk, D., C. Wilson, J. F. Passos, F. Oakley, C. Correia-Melo, L. Greaves, G. Saretzki, C. Fox, C. Lawless, R. Anderson, G. Hewitt, S. L. Pender, N. Fullard, G. Nelson, J. Mann, B. van de Sluis, D. A. Mann, and T. von Zglinicki. 2014. 'Chronic inflammation induces telomere dysfunction and accelerates ageing in mice', Nat Commun, 2: 4172.
Justice, N. J. 2018. 'The relationship between stress and Alzheimer's disease', Neurobiol Stress, 8: 127-33.
Kawano, Y., T. Yoshimura, D. Tsuboi, S. Kawabata, T. Kaneko-Kawano, H. Shirataki, T. Takenawa, and K. Kaibuchi. 2005. 'CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation', Mol Cell Biol, 25: 9920-35.
Keeney, A., D. S. Jessop, M. S. Harbuz, C. A. Marsden, S. Hogg, and R. E. Blackburn-Munro. 2006. 'Differential effects of acute and chronic social defeat stress on hypothalamic-pituitary-adrenal axis function and hippocampal serotonin release in mice', J Neuroendocrinol, 18: 330-8.
Kendler, K. S., L. M. Karkowski, and C. A. Prescott. 1999. 'Causal relationship between stressful life events and the onset of major depression', Am J Psychiatry, 156: 837-41.
Kessler, R. C., W. T. Chiu, O. Demler, K. R. Merikangas, and E. E. Walters. 2005. 'Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication', Arch Gen Psychiatry, 62: 617-27.
Kirkland, J. L., T. Tchkonia, Y. Zhu, L. J. Niedernhofer, and P. D. Robbins. 2017. 'The Clinical Potential of Senolytic Drugs', J Am Geriatr Soc, 65: 2297-301.
Krishnan, V., and E. J. Nestler. 2011. 'Animal models of depression: molecular perspectives', Curr Top Behav Neurosci, 7: 121-47.
Lara, V. P., P. Caramelli, A. L. Teixeira, M. T. Barbosa, K. C. Carmona, M. G. Carvalho, A. P. Fernandes, and K. B. Gomes. 2013. 'High cortisol levels are associated with cognitive impairment no-dementia (CIND) and dementia', Clin Chim Acta, 423: 18-22.
Lee, H. K., K. Takamiya, J. S. Han, H. Man, C. H. Kim, G. Rumbaugh, S. Yu, L. Ding, C. He, R. S. Petralia, R. J. Wenthold, M. Gallagher, and R. L. Huganir. 2003. 'Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory', Cell, 112: 631-43.
Leung, T., Y. Ng, A. Cheong, C. H. Ng, I. Tan, C. Hall, and L. Lim. 2002. 'p80 ROKalpha binding protein is a novel splice variant of CRMP-1 which associates with CRMP-2 and modulates RhoA-induced neuronal morphology', FEBS Lett, 532: 445-9.
Li, Y., L. Ning, Y. Yin, R. Wang, Z. Zhang, L. Hao, B. Wang, X. Zhao, X. Yang, L. Yin, S. Wu, D. Guo, and C. Zhang. 2020. 'Age-related shifts in gut microbiota contribute to cognitive decline in aged rats', Aging (Albany NY), 12: 7801-17.
Lieberman, J. A., R. R. Girgis, G. Brucato, H. Moore, F. Provenzano, L. Kegeles, D. Javitt, J. Kantrowitz, M. M. Wall, C. M. Corcoran, S. A. Schobel, and S. A. Small. 2018. 'Hippocampal dysfunction in the pathophysiology of schizophrenia: a selective review and hypothesis for early detection and intervention', Mol Psychiatry, 23: 1764-72.
Lin, Y. S., Y. F. Lin, K. C. Chen, Y. K. Yang, and Y. H. Hsiao. 2019. 'Collapsin response mediator protein 5 (CRMP5) causes social deficits and accelerates memory loss in an animal model of Alzheimer's disease', Neuropharmacology, 157: 107673.
Lopes, S., J. Vaz-Silva, V. Pinto, C. Dalla, N. Kokras, B. Bedenk, N. Mack, M. Czisch, O. F. Almeida, N. Sousa, and I. Sotiropoulos. 2016. 'Tau protein is essential for stress-induced brain pathology', Proc Natl Acad Sci U S A, 113: E3755-63.
Mattson, M. P., and T. V. Arumugam. 2018. 'Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States', Cell Metab, 27: 1176-99.
Miller, S. M., and A. Sahay. 2019. 'Functions of adult-born neurons in hippocampal memory interference and indexing', Nat Neurosci, 22: 1565-75.
Ogrodnik, M., Y. Zhu, L. G. P. Langhi, T. Tchkonia, P. Kruger, E. Fielder, S. Victorelli, R. A. Ruswhandi, N. Giorgadze, T. Pirtskhalava, O. Podgorni, G. Enikolopov, K. O. Johnson, M. Xu, C. Inman, A. K. Palmer, M. Schafer, M. Weigl, Y. Ikeno, T. C. Burns, J. F. Passos, T. von Zglinicki, J. L. Kirkland, and D. Jurk. 2019. 'Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis', Cell Metab, 29: 1061-77 e8.
Passos, J. F., G. Nelson, C. Wang, T. Richter, C. Simillion, C. J. Proctor, S. Miwa, S. Olijslagers, J. Hallinan, A. Wipat, G. Saretzki, K. L. Rudolph, T. B. Kirkwood, and T. von Zglinicki. 2010. 'Feedback between p21 and reactive oxygen production is necessary for cell senescence', Mol Syst Biol, 6: 347.
Peavy, G. M., D. P. Salmon, M. W. Jacobson, A. Hervey, A. C. Gamst, T. Wolfson, T. L. Patterson, S. Goldman, P. J. Mills, S. Khandrika, and D. Galasko. 2009. 'Effects of chronic stress on memory decline in cognitively normal and mildly impaired older adults', Am J Psychiatry, 166: 1384-91.
Porterfield, V., S. S. Khan, E. P. Foff, M. M. Koseoglu, I. K. Blanco, S. Jayaraman, E. Lien, M. J. McConnell, G. S. Bloom, J. S. Lazo, and E. R. Sharlow. 2020. 'A three-dimensional dementia model reveals spontaneous cell cycle re-entry and a senescence-associated secretory phenotype', Neurobiol Aging, 90: 125-34.
Quach, T. T., J. Honnorat, P. E. Kolattukudy, R. Khanna, and A. M. Duchemin. 2015. 'CRMPs: critical molecules for neurite morphogenesis and neuropsychiatric diseases', Mol Psychiatry, 20: 1037-45.
Ribeiro, L. R., I. D. Della-Pace, A. P. de Oliveira Ferreira, V. R. Funck, S. Pinton, F. Bobinski, C. V. de Oliveira, F. da Silva Fiorin, M. M. Duarte, A. F. Furian, M. S. Oliveira, C. W. Nogueira, A. R. Dos Santos, L. F. Royes, and M. R. Fighera. 2013. 'Chronic administration of methylmalonate on young rats alters neuroinflammatory markers and spatial memory', Immunobiology, 218: 1175-83.
Richter-Levin G, Xu L. 2018. 'How could stress lead to major depressive disorder?', IBRO reports, 4: 38-43.
Rosslenbroich, V., L. Dai, S. L. Baader, A. A. Noegel, V. Gieselmann, and J. Kappler. 2005. 'Collapsin response mediator protein-4 regulates F-actin bundling', Exp Cell Res, 310: 434-44.
Salleh, M. R. 2008. 'Life event, stress and illness', Malays J Med Sci, 15: 9-18.
Satoh, A., S. I. Imai, and L. Guarente. 2017. 'The brain, sirtuins, and ageing', Nat Rev Neurosci, 18: 362-74.
Shors, T. J., and E. Dryver. 1994. 'Effect of stress and long-term potentiation (LTP) on subsequent LTP and the theta burst response in the dentate gyrus', Brain Res, 666: 232-8.
Shrestha, A., M. Roach, K. Joshi, J. J. Sheehan, P. Goutam, K. Everson, K. Heerlein, and A. B. Jena. 2020. 'Incremental Health Care Burden of Treatment-Resistant Depression Among Commercial, Medicaid, and Medicare Payers', Psychiatr Serv, 71: 593-601.
Stone, S. S., C. M. Teixeira, L. M. Devito, K. Zaslavsky, S. A. Josselyn, A. M. Lozano, and P. W. Frankland. 2011. 'Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory', J Neurosci, 31: 13469-84.
Tada, S., M. Furuta, K. Fukada, D. Hirozawa, M. Matsui, F. Aoike, T. Okuno, J. Sawada, H. Mochizuki, and T. Hazama. 2016. 'Severe parkinsonism associated with anti-CRMP5 antibody-positive paraneoplastic neurological syndrome and abnormal signal intensity in the bilateral basal ganglia', J Neurol Neurosurg Psychiatry, 87: 907-10.
Tian, R., G. Hou, D. Li, and T. F. Yuan. 2014. 'A possible change process of inflammatory cytokines in the prolonged chronic stress and its ultimate implications for health', ScientificWorldJournal, 2014: 780616.
Tominaga, K., and H. I. Suzuki. 2019. 'TGF-beta Signaling in Cellular Senescence and Aging-Related Pathology', Int J Mol Sci, 20.
Turner, A. D., A. W. Capuano, R. S. Wilson, and L. L. Barnes. 2015. 'Depressive symptoms and cognitive decline in older african americans: two scales and their factors', Am J Geriatr Psychiatry, 23: 568-78.
Uchida, Y., T. Ohshima, N. Yamashita, M. Ogawara, Y. Sasaki, F. Nakamura, and Y. Goshima. 2009. 'Semaphorin3A signaling mediated by Fyn-dependent tyrosine phosphorylation of collapsin response mediator protein 2 at tyrosine 32', J Biol Chem, 284: 27393-401.
van Deursen, J. M. 2014. 'The role of senescent cells in ageing', Nature, 509: 439-46.
von Kobbe, C. 2019. 'Targeting senescent cells: approaches, opportunities, challenges', Aging (Albany NY), 11: 12844-61.
Wada, S., J. Yanagida, H. Sasase, T. Zhang, X. Li, H. Kamii, M. Domoto, S. Deyama, E. Hinoi, A. Yamanaka, N. Nishitani, K. Nagayasu, S. Kaneko, M. Minami, and K. Kaneda. 2020. 'Acute restraint stress augments the rewarding memory of cocaine through activation of alpha1 adrenoceptors in the medial prefrontal cortex of mice', Neuropharmacology, 166: 107968.
Wang, X. L., D. Q. Wang, F. C. Jiao, K. M. Ding, Y. B. Ji, L. Lu, K. Yuan, G. F. Gao, and S. X. Li. 2020. 'Diurnal rhythm disruptions induced by chronic unpredictable stress relate to depression-like behaviors in rats', Pharmacol Biochem Behav, 194: 172939.
Wiley, C. D., M. C. Velarde, P. Lecot, S. Liu, E. A. Sarnoski, A. Freund, K. Shirakawa, H. W. Lim, S. S. Davis, A. Ramanathan, A. A. Gerencser, E. Verdin, and J. Campisi. 2016. 'Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype', Cell Metab, 23: 303-14.
Wissler Gerdes, E. O., Y. Zhu, T. Tchkonia, and J. L. Kirkland. 2020. 'Discovery, development, and future application of senolytics: theories and predictions', FEBS J, 287: 2418-27.
Wojtowicz, J. M., and N. Kee. 2006. 'BrdU assay for neurogenesis in rodents', Nat Protoc, 1: 1399-405.
Yamashita, N., B. Mosinger, A. Roy, M. Miyazaki, K. Ugajin, F. Nakamura, Y. Sasaki, K. Yamaguchi, P. Kolattukudy, and Y. Goshima. 2011. 'CRMP5 (collapsin response mediator protein 5) regulates dendritic development and synaptic plasticity in the cerebellar Purkinje cells', J Neurosci, 31: 1773-9.
Yang, L., Y. Zhao, Y. Wang, L. Liu, X. Zhang, B. Li, and R. Cui. 2015. 'The Effects of Psychological Stress on Depression', Curr Neuropharmacol, 13: 494-504.
Yap, S. M., T. Lynch, P. MacMahon, and B. Murray. 2017. 'Paraneoplastic Atypical Parkinsonism with Anti-CRMP5 Antibodies and Severe Caudate and Putaminal Hypometabolism on 18-Fluorodeoxyglucose Positron Emission Tomography of the Brain', Mov Disord Clin Pract, 4: 263-65.
Zhang, P., Y. Kishimoto, I. Grammatikakis, K. Gottimukkala, R. G. Cutler, S. Zhang, K. Abdelmohsen, V. A. Bohr, J. Misra Sen, M. Gorospe, and M. P. Mattson. 2019. 'Senolytic therapy alleviates Abeta-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model', Nat Neurosci, 22: 719-28.