Notch1 signaling related hippocampal neurogenesis in adult poststroke depression rats: a valid index for an efficient combined citalopram and WAY100635 pharmacotherapy.
We investigated the hypothesis that hippocampal neurogenesis related to Notch1 signaling could be a valid index for a combined citalopram and WAY100635 pharmacotherapy for the treatment of depression arising after stroke. Adult rats were exposed to a chronic mild stress paradigm after ischemic surgery. Behavioral tests included the open-field test and a sucrose consumption test. Proliferating cells in the hippocampus ipsilateral to ischemia and their fate were monitored by bromodeoxyuridine labeling and confocal laser scanning microscopy for up to 28 days (day 28) after ischemia. Expression of the Notch1 signaling cascade, including its ligand and downstream target genes, was also examined. WAY100635 shortened the onset of citalopram action to less than the day 21 required with citalopram alone and also proved more effective. The activity of the Notch1 signaling pathway in the hippocampus fluctuated in its function in proliferation (day 21) and differentiation (day 28) of newly formed cells in animals receiving the combination treatment. This indicated that augmentation of citalopram by cotreatment with a selective 5-hydroxytryptamine 1A antagonist would be an efficacious strategy for poststroke depression. The observed effects are most likely because of enhanced poststroke neurogenesis mediated by the Notch1 signaling cascade.
Wang
Shao-Hua
SH
The Department of Neurology, ZhongDa Hospital of Southeast Universit, Nanjing 210009, PR China.
Zhang
Zhi-Jun
ZJ
Guo
Yi-Jing
YJ
Sui
Yu-Xiu
YX
Sun
Yi
Y
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015283:Citalopram / Q000008:administration & dosage*; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D010879:Piperazines / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D012702:Serotonin Antagonists / Q000008:administration & dosage; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects*
D015283:Citalopram; D010879:Piperazines; D011725:Pyridines; D051881:Receptor, Notch1; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C497763:Notch1 protein, rat; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide