Chronic but not acute foot-shock stress leads to temporary suppression of cell proliferation in rat hippocampus.
Stressful experiences, especially when prolonged and severe are associated with psychopathology and impaired neuronal plasticity. Among other effects on the brain, stress has been shown to negatively regulate hippocampal neurogenesis, and this effect is considered to be exerted via glucocorticoids. Here, we sought to determine the temporal dynamics of changes in hippocampal neurogenesis after acute and chronic exposure to foot-shock stress. Rats subjected to a foot-shock procedure showed strong activation of the hypothalamic-pituitary-adrenal (HPA) axis, even after exposure to daily stress for 3 weeks. Despite a robust release of corticosterone, acute foot-shock stress did not affect the rate of hippocampal cell proliferation. In contrast, exposure to foot-shock stress daily for 3 weeks led to reduced cell proliferation 2 hours after the stress procedure. Interestingly, this stress-induced effect did not persist and was no longer detected 24 hours later. Also, while chronic foot-shock stress had no impact on survival of hippocampal cells that were born before the stress procedure, it led to a decreased number of doublecortin-positive granule neurons that were born during the chronic stress period. Thus, whereas a strong activation of the HPA axis during acute foot-shock stress is not sufficient to reduce hippocampal cell proliferation, repeated exposure to stressful stimuli for prolonged period of time ultimately results in dysregulated neurogenesis. In sum, this study supports the notion that chronic stress may lead to cumulative changes in the brain that are not seen after acute stress. Such changes may indicate compromised brain plasticity and increased vulnerability to neuropathology.
Dagyte
G
G
Department of Molecular Neurobiology, University of Groningen, PO Box 14, 9750 AA, Haren, The Netherlands. G.Dagyte@student.rug.nl
Van der Zee
E A
EA
Postema
F
F
Luiten
P G M
PG
Den Boer
J A
JA
Trentani
A
A
Meerlo
P
P
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001835:Body Weight; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D003345:Corticosterone / Q000097:blood; D000089662:Doublecortin Protein; D004435:Eating; D006624:Hippocampus / Q000473:pathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D014828:Vocalization, Animal
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone