title: Learned helplessness activates hippocampal microglia in rats: A potential target for the antidepressant imipramine.
abstract: An accumulating body of evidence has demonstrated that inflammation is associated with the pathology of depression. We recently found that psychological stress induces inflammation in the hippocampus of the rat brain through the inflammasome, a component of the innate immune system. Microglia, the resident macrophages in the brain, play a central role in the innate immune system and express inflammasomes; thus, we hypothesized that hippocampal microglia would be key mediators in the development of depression via stress-induced inflammation. To test this hypothesis and to determine how antidepressants modulate microglial function, we used immunohistochemistry to examine the morphological changes that occur in the hippocampal microglia of rats exposed to the learned helplessness (LH) paradigm. We noted significantly increased numbers of activated microglia in the granule cell layer, hilus, CA1, and CA3 regions of the hippocampi of LH rats. Conversely, administering imipramine to LH rats for 7days produced a significant decrease in the number of activated microglia in the hilus, but not in the other examined regions. Nonetheless, there were no significant differences in the combined number of activated and non-activated microglia either in LH or LH+imipramine rats relative to control rats. In addition, treating the naïve rats with imipramine or fluvoxamine produced no discernible microglial changes. These data suggest that stress activates hippocampal microglia, while certain antidepressants decrease the number of activated microglia in the hilus, but not in other hippocampal regions. Therefore, the hilus represents a candidate target region for the antidepressant imipramine.
authors: Department of Neuropsychiatry, Faculty of Medicine, Tottori University, Yonago, Japan.
authors: Masaaki
authors: M
authors: Iwata
authors: Department of Neuropsychiatry, Faculty of Medicine, Tottori University, Yonago, Japan.
authors: Hisahito
authors: H
authors: Ishida
authors: Department of Neuropsychiatry, Faculty of Medicine, Tottori University, Yonago, Japan.
authors: Koichi
authors: K
authors: Kaneko
authors: Department of Psychiatry, Teikyo University Chiba Medical Center, Ichihara, Japan. Electronic address: shirayama@rapid.ocn.ne.jp.
authors: Yukihiko
authors: Y
authors: Shirayama
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D006380:Helplessness, Learned; D006624:Hippocampus / Q000502:physiology*; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D017628:Microglia / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000928:Antidepressive Agents; D007099:Imipramine
keywords: Antidepressants; Depression; Hippocampus; Learned helplessness; Microglia