Hippocampal neurogenesis and behavioural studies on adult ischemic rat response to chronic mild stress.
Stress and antidepressants have been shown to influence hippocampal neurogenesis, which is hypothesized to be an etiological factor of depression. Robust ischemia-stimulated neurogenesis implies the existence of an innate response and rehabilitation mechanism to injury repair, i.e. cognitive recovery. We investigated whether unpredictable chronic mild stress (CMS) influences ischemia-stimulated compensatory neurogenesis in the hippocampus and also studied the therapeutic effect of citalopram. Adult rats were exposed to the CMS paradigm after left middle cerebral artery occlusion (MCAO). The open-field test (OFT) and the sucrose consumption test were employed to assess depression-like behaviour. The survival and fate of proliferating cells was monitored by labelling with bromodeoxyuridine (BrdU) and other cell markers. Cell proliferation was examined 1 day after the last BrdU injection, and survival and differentiation were determined up to 45 days after ischemia. The number of BrdU-positive cells that were labelled using the 2 protocols and the proportion of newborn neurons in the dentate gyrus (DG) ipsilateral to ischemia were higher than in the control. CMS induced depressive behaviours in ischemic rats, and this was accompanied by reduced proliferation and survival/neurogenic fate. All these effects were reversed by citalopram administration. These results support a putative role for ischemia-induced neurogenesis in what may be an adaptive or compensatory process, which is influenced by post-stroke stressors. This may contribute to the onset of Post-stroke depression (PSD) and thus represents a potential target for therapy.
Wang
Shao-hua
SH
Department of Neurology and Institution of Cerebral Vascular Disease, ZhongDa Hospital of Southeast University, Nanjing 210009, JiangSu Province, China.
Zhang
Zhi-jun
ZJ
Guo
Yi-jing
YJ
Teng
Gao-jun
GJ
Chen
Bao-an
BA
D000222:Adaptation, Physiological / Q000187:drug effects; D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D015283:Citalopram / Q000494:pharmacology; D003863:Depression / Q000517:prevention & control; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D008297:Male; D016555:Matched-Pair Analysis; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications / Q000473:pathology*
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram