Stress-induced suppression of hippocampal neurogenesis in adult male rats is altered by prenatal ethanol exposure.
In adulthood, both alcohol (ethanol) and stress are known to suppress hippocampal neurogenesis in male rats. Similarly, most studies report that prenatal alcohol exposure (PAE) reduces cell proliferation and/or cell survival in the hippocampus of adult males. Furthermore, PAE is known to have marked effects on behavioral and hypothalamic-pituitary-adrenal (HPA) responsiveness to stressors. However, no studies have examined the modulation of adult hippocampal neurogenesis by stress in PAE animals. We hypothesized that, in accordance with previous data, PAE would suppress basal levels of adult hippocampal neurogenesis, and further that stress acting on a sensitized HPA axis would have greater adverse effects on adult hippocampal neurogenesis in PAE than in control rats. Adult male offspring from PAE, pair-fed (PF) control, and ad libitum-fed control (C) groups were subjected to restraint stress (9 days, 1 h/day) or left undisturbed. Rats were then injected with bromodeoxyuridine (BrdU) on day 10, perfused 24 h (proliferation) or 3 weeks (survival) later, and brains processed for BrdU immunohistochemistry. We found that (1) under non-stressed conditions, PAE rats had a small but statistically significant suppressive effect on levels of hippocampal neurogenesis and (2) unexpectedly, repeated restraint stress significantly reduced neurogenesis in C and PF, but not PAE rats. We speculate that the failure of PAE males to mount an appropriate (i.e. suppressive) neurogenic response to stressors, implies reduced plasticity and adaptability or resilience, which could impact negatively on hippocampal structure and function.
Department of Cellular and Physiological Sciences, The University of the British Columbia, Vancouver, BC, V6T 1Z3, Canada. sliwowsk@interchange.ubc.ca
J H
JH
Sliwowska
J M
JM
Barker
C K
CK
Barha
N
N
Lan
J
J
Weinberg
L A M
LA
Galea
D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*
D000431:Ethanol; D003345:Corticosterone