Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 33, Issue 4, Pages 688-694Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2009.03.022
Keywords
Depression; Ischemia; Notch signaling pathway; Neurogenesis; Stroke
Funding
- National Natural Science Foundation of China [30600206, 30870870]
- Nature Science Intensive Fund of JiangSu province [BK2008302]
- National Nature Science Foundation of China for the Excellent Young Scientist [30825014]
Ask authors/readers for more resources
Accumulating evidence indicates that the Notch signaling pathway fulfills important roles in ischemia-stimulated neurogenesis, which may be regarded as an etiological factor in post-stroke depression. Here we explored Notch, signaling, hippocampal neurogenesis and behavioral responses to chronic unpredicted mild stress (CUMS) in adult ischemic rats. Animals were treated with permanent middle cerebral artery occlusion followed by an 18 day CUMS procedure. Proliferating cells in the hippocampus and their cell fate were investigated on days 19 and 28 after ischemic surgery. Additionally, expression of the Notch, intracellular domain (NICD) and its downstream targets Hes1 and Hes5 was examined. A sucrose preference test and forced swim test were used to assess behavioral responses. CUMS produced depressive-like behaviors and decreased the number of proliferating cells on day 19 (both p<0.001), accompanied by a decreased expression of both Hes1 and Hes5 in the hippocampus of ischemic animals (p<0.001). On day 28, CUMS resulted in a decreased number of neurogenically-differentiating cells in the subgranular zone (p<0.001) while permitting differentiation into astrocytes in the hilus (p<0.05). Hes1 and Hes5 protein expression levels were increased. The expression of the NICD was significantly decreased at both time-points. CUMS led to expression changes in the Notch, signaling cascade in ischemic rats, most of which concerned hippocampal neurogenesis. This suggests that variation in Notch, activity and subsequent expression of its downstream targets, including Hes1 and Hes5, may, at least in part, contribute to modulation of ischemia-related hippocampal neurogenesis by CUMS. (C) 2009 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available