title: Postischemic Anhedonia Associated with Neurodegenerative Changes in the Hippocampal Dentate Gyrus of Rats.
abstract: Poststroke depression is one of the major symptoms observed in the chronic stage of brain stroke such as cerebral ischemia. Its pathophysiological mechanisms, however, are not well understood. Using the transient right middle cerebral artery occlusion- (MCAO-, 90 min) operated rats as an ischemia model in this study, we first observed that aggravation of anhedonia spontaneously occurred especially after 20 weeks of MCAO, and it was prevented by chronic antidepressants treatment (imipramine or fluvoxamine). The anhedonia specifically associated with loss of the granular neurons in the ipsilateral side of hippocampal dentate gyrus and was also prevented by an antidepressant imipramine. Immunohistochemical analysis showed increased apoptosis inside the granular cell layer prior to and associated with the neuronal loss, and imipramine seemed to recover the survival signal rather than suppressing the death signal to prevent neurons from apoptosis. Proliferation and development of the neural stem cells were increased transiently in the subgranular zone of both ipsi- and contralateral hippocampus within one week after MCAO and then decreased and almost ceased after 6 weeks of MCAO, while chronic imipramine treatment prevented them partially. Overall, our study suggests new insights for the mechanistic correlation between poststroke depression and the delayed neurodegenerative changes in the hippocampal dentate gyrus with effective use of antidepressants on them.
authors.affiliation: Department of Neurobiology and Therapeutics, Institute of Biomedical Sciences, Graduate School and Faculty of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8505, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Kasahara
authors.affiliation: Department of Neurobiology and Therapeutics, Institute of Biomedical Sciences, Graduate School and Faculty of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8505, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Department of Neurobiology and Therapeutics, Institute of Biomedical Sciences, Graduate School and Faculty of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8505, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Tezuka
authors.affiliation: Department of Neurobiology and Therapeutics, Institute of Biomedical Sciences, Graduate School and Faculty of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8505, Japan.
authors.forename: Nanae
authors.initials: N
authors.lastname: Oka
mesh_terms: D059445:Anhedonia / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D002545:Brain Ischemia / Q000473:pathology / Q000523:psychology*; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D016666:Fluvoxamine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000523:psychology*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000928:Antidepressive Agents; D016666:Fluvoxamine; D007099:Imipramine