在人類已有不少研究指出「社會支持」不論對於生理疾病(例如高血壓等)或是心理疾病(例如憂鬱症等)都具有調節的作用。當受到壓力的時候，壓力會使人體血液內的皮質醇濃度或老鼠血液內的腎上腺皮質酮濃度上升。壓力也會造成中樞神經系統一些特定區域神經新生的情形降低。而社會支持包含親屬朋友間的良好互動、實質幫助、鼓勵及陪伴等等正面的影響力，本研究主要探討同伴陪伴這其中一種。我們利用小鼠的模式來探討處於壓力時的同伴陪伴對於壓力造成的神經新生數目降低是否有緩解的作用。首先藉由測量血清中腎上腺皮質酮濃度的高低代表不同壓力事件的強度，並在老鼠接受壓力前先腹腔注射一劑Bromodeoxyuridine (BrdU, 100mg/kg, i.p.)以標定新生的細胞。我們發現老鼠經歷無規則時距的電刺激(unexpected electrical foot shock)三十次及泡在水中的禁錮(constraint in water)可以造成血清中的腎上腺皮質酮濃度迅速明顯上升，而在壓力之後三個小時則會降回基礎值；為了增加壓力事件的持續影響力，我們持續給予小鼠電刺激及禁錮兩種壓力，並以此當做實驗的主要壓力程序。在小鼠經歷壓力時，分別有獨自經歷、與熟識同伴或具有熟識同伴味道的木塊一起經歷、與不熟識同伴(不同籠的小鼠)或不熟悉木塊一起經歷等組別。當小鼠經歷壓力後3小時及6小時分別灌流取腦以進行免疫組織化學染色。我們發現接續壓力確實造成血液中腎上腺皮質酮濃度上升並抑制海馬齒狀迴的神經新生，但對於腦室下區的神經新生幾乎沒有影響；經歷壓力時，不論是熟悉或不熟悉的同伴陪伴，以及熟悉或不熟悉同伴的氣味陪伴都可以減緩壓力抑制海馬齒狀迴的神經新生，但並不影響壓力刺激腎上腺皮質酮的分泌。顯示當經歷壓力時，同伴的陪伴可以減除壓力抑制的神經新生，但此減緩的原因並非經由抑制壓力荷爾蒙的分泌達成。

Many studies have indicated that social support acts as a moderating factor on physical and psychological diseases such as hypertension and depression in hunam. Both psychological and physical stress has been reported to increase cortisol (in human) or corticosterone (CORT in mice) concentration and diminish neurogenesis. The term “social support” often included a broad sense, such as the positive emotional support from amicable network of relatives, friends and coworkers, helps, tangible encouragement, and so on. The conspecific companions were the kind of social support. It was undertaken to study the modulating effect of social support on stress-decreased neurogenesis in mice. We measured serum CORT concentration to reveal the stress magnitude. We found that mice undergoing stress (including constraint in water and unexpected electrical foot shock) exhibited an increased CORT concentration at 30 min following the stress exposure. Such an increased CORT concentration was back to basal levels at 3 hours post stress. In an attempt to maximize the stress effect, shock and constraint stress were combined in a secquence. Bromodeoxyuridine (BrdU, 100mg/kg, i.p. injection prior to stress treatment) was used to label neuroprogenitor cells. We injected intraperitoneally each mice a dose of BrdU prior to the combined stress treatment. Mice experienced the stress events alone, or along with three familiar companions or odor-familiar wooden blocks, or along with three unfamiliar companions or odor-unfamiliar wooden blocks from different cages. Mice were then perfused at three or six hours after last stress for quantifying the BrdU and BrdU/Dcx positive cells in the dentate gyrus and subventricular zone. We found that stress did stimulate serum corticosterone level and diminish neurogenesis in the dentate gyrus. Social support from conspecific (familiar and unfamiliar) companions or presence of their familiar and unfamiliar odors did reverse stress-decreased neurogenesis in the dentate gurus. However, mice experienced stress with conspecific companions didn’t affect the CORT level response to stress. These results suggested that exposure to social support throughout the stress may alleviate stress-decreasing effect on neurogenesis, but the modulating effect wasn’t cause by inhibition of stress hormone secretion.

1. Anisman H, Prakash P, Merali Z, Poulter MO (2007). Corticotropin releasing hormone receptor alterations elicited by acute and chronic unpredictable stressor challenges in stressor-susceptible and resilient strains of mice. Behav Brain Res. 181(2):180-90.
2. Brown SL, Nesse RM, Vinokur AD, Smith DM (2003). Providing social support may be more beneficial than receiving it: results from a prospective study of mortality. Psychol Sci. 14(4):320-7.
3. Cameron HA and McKay RD (1999). Restoring production of hippocampal neurons in old age. Nat Neurosci. 2(10):894-7.
4. Cobb S. (1976). Presidential Address-1976. Social support as a moderator of life stress. Psychosom Med. 38(5):300-14.
5. Coe CL (1993). Psychosocial factors and immunity in nonhuman primates: a review. Psychosom. Med 55(3):298-308.
6. Cohen S. (1988). Psychosocial models of the role of social support in the etiology of physical disease. Health Psychol. 7(3):269-97.
7. Cohen S and Wills TA (1985). Stress, social support, and the buffering hypothesis. Psychol Bull. 98(2):310-57.
8. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E (2001). Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA 98:12796–12801.
9. Czeh B, Welt T, Fischer AK, Erhardt A, Schmitt W, Muller MB, Toschi N, Fuchs E, Keck ME (2002). Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis. Biol Psychiatry 52:1057–1065.
10. De Kloet ER, Derijk R. (2004). Signaling pathways in brain involved in predisposition and pathogenesis of stress-related disease: genetic and kinetic factors affecting the MR/GR balance. Ann N Y Acad Sci. 1032:14-34.
11. De Kloet ER, Karst H, Joëls M (2008). Corticosteroid hormones in the central stress response: quick-and-slow. Front Neuroendocrinol. 29(2):268-72.
12. DeVries AC, Glasper ER, Detillion CE (2003). Social modulation of stress responses. Physiol Behav. 79(3):399-407.
13. Engelmann M, Landgraf R, Wotjak CT (2004). The hypothalamic - neurohypophysial system regulates the hypothalamic–pituitary-adrenal axis under stress: an old concept revisited. Front Neuroendocrinol. 25(3-4):132-49.
14. Fischer Aggarwal BA, Liao M, Mosca L. Physical activity as a potential mechanism through which social support may reduce cardiovascular disease risk. J Cardiovasc Nurs. 23(2):90-6.
15. Fuchs E, Flugge G (1998). Stress, glucocorticoids and structural plasticity of the hippocampus. Neurosci Biobehav Rev 23:295–300.
16. Gould E (2007). How widespread is adult neurogenesis in mammals? Nat Rev Neurosci. 8(6):481-8.
17. Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E (1998). Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci USA 95:3168–3171.
18. Gould E, Woolley CS, Cameron HA, Daniels DC, McEwen BS. (1991) Adrenal steroids regulate postnatal development of the rat dentate gyrus: II. Effects of glucocorticoids and mineralocorticoids on cell birth. J Comp Neurol. 15; 313(3):486-93.
19. Jacobs BL, van Praag H, Gage FH (2000). Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 5:262–269.
20. Jacobs BL, van Praag H, Gage FH (2000). Depression and the birth and death of brain cells. Am Sci 88:340–345.
21. Kee N., Teixeira CM, Wang AH, Frankland PW. (2007) Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nature Neuroscience 10, 355 – 362
22. Kessler RC (1997). The effects of stressful life events on depression. Annu Rev Psychol 48:191–214.
23. Malberg JE, Duman RS (2003). Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology 28:1562–1571.
24. Mirescu C, Gould E. (2006) Stress and adult neurogenesis. Hippocampus. 16(3):233-8.
25. Palme R, Rettenbacher S, Touma C, El-Bahr SM, Möstl E. (2005). Stress hormones in mammals and birds: comparative aspects regarding metabolism, excretion, and noninvasive measurement in fecal samples. Ann N Y Acad Sci. 1040:162-71.
26. Pham K, Nacher J, Hof PR, McEwen BS (2003). Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci 17:879–886.
27. Swiergiel AH, Leskov IL, Dunn AJ (2008). Effects of chronic and acute stressors and CRF on depression-like behavior in mice. Behav Brain Res. 186(1):32-40.
28. Thomas RM, Hotsenpiller G, Peterson DA (2007). Acute psychosocial stress reduces cell survival in adult hippocampal neurogenesis without altering proliferation. J Neurosci 27(11):2734-43.