Chikama Koji, Yamada Hidetaka, Tsukamoto Tatsuo, Kajitani Kosuke, Nakabeppu Yusaku, Uchimura Naohisa
Department of Neuropsychiatry, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
Department of Neuropsychiatry, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan; Department of Psychiatry, Center for Memory and Aging, Kurume University Medical Center, 155-1 Kokubumachi, Kurume, Fukuoka 839-0863, Japan.
Brain Res. 2017 Dec 1;1676:77-82. doi: 10.1016/j.brainres.2017.09.006. Epub 2017 Sep 9.
It is suggested that altered neuroplasticity contributes to the pathophysiology of schizophrenia and antipsychotics may exhibit some of their therapeutic efficacies by improving neurogenesis and/or proliferation of neural progenitors. The aim of this study is to investigate whether chronic antipsychotics treatment affect neurogenesis in adult mouse hippocampus. Animals were administered olanzapine, quetiapine, clozapine, risperidone, aripiprazole, or haloperidol via the osmotic minipump for 21days and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. BrdU-positive cells in the hippocampus were quantified by stereology. Aripiprazole, quetiapine, clozapine, and olanzapine significantly increased density of BrdU-positive cells in the hippocampus. Interestingly, other antipsychotic drugs had tendency to increasing BrdU-positive cells, whereas haloperidol had propensity to decrease with a marginal significance. These results suggest that differences of neurogenesis among these drugs may, at least in part, account for their pharmacological profiles.
有人认为，神经可塑性改变促成了精神分裂症的病理生理学，抗精神病药物可能通过改善神经发生和/或神经祖细胞的增殖而发挥其部分治疗功效。本研究的目的是调查长期使用抗精神病药物治疗是否会影响成年小鼠海马体中的神经发生。通过渗透微型泵给动物施用奥氮平、喹硫平、氯氮平、利培酮、阿立哌唑或氟哌啶醇，持续21天，然后注射5-溴-2'-脱氧尿苷（BrdU）以标记有丝分裂细胞。通过体视学对海马体中BrdU阳性细胞进行定量。阿立哌唑、喹硫平、氯氮平和奥氮平显著增加了海马体中BrdU阳性细胞的密度。有趣的是，其他抗精神病药物有增加BrdU阳性细胞的趋势，而氟哌啶醇有减少BrdU阳性细胞的倾向，且具有边缘显著性。这些结果表明，这些药物之间神经发生的差异可能至少部分地解释了它们的药理学特征。
