Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.
Laboratory of Nutritional Brain Science, Department of Food Science and Nutrition, Mukogawa Women's University, Nishinomiya, Hyogo, 663-8558, Japan.
Mol Brain. 2019 Aug 5;12(1):69. doi: 10.1186/s13041-019-0489-5.
The selective serotonin reuptake inhibitor fluoxetine (FLX) is widely used to treat depression and anxiety disorders. Chronic FLX treatment reportedly induces cellular responses in the brain, including increased adult hippocampal and cortical neurogenesis and reversal of neuron maturation in the hippocampus, amygdala, and cortex. However, because most previous studies have used rodent models, it remains unclear whether these FLX-induced changes occur in the primate brain. To evaluate the effects of FLX in the primate brain, we used immunohistological methods to assess neurogenesis and the expression of neuronal maturity markers following chronic FLX treatment (3 mg/kg/day for 4 weeks) in adult marmosets (n = 3 per group). We found increased expression of doublecortin and calretinin, markers of immature neurons, in the hippocampal dentate gyrus of FLX-treated marmosets. Further, FLX treatment reduced parvalbumin expression and the number of neurons with perineuronal nets, which indicate mature fast-spiking interneurons, in the hippocampus, but not in the amygdala or cerebral cortex. We also found that FLX treatment increased the generation of cortical interneurons; however, significant up-regulation of adult hippocampal neurogenesis was not observed in FLX-treated marmosets. These results suggest that dematuration of hippocampal neurons and increased cortical neurogenesis may play roles in FLX-induced effects and/or side effects. Our results are consistent with those of previous studies showing hippocampal dematuration and increased cortical neurogenesis in FLX-treated rodents. In contrast, FLX did not affect hippocampal neurogenesis or dematuration of interneurons in the amygdala and cerebral cortex.
选择性 5-羟色胺再摄取抑制剂氟西汀（FLX）被广泛用于治疗抑郁症和焦虑症。据报道，慢性 FLX 治疗会引起大脑中的细胞反应，包括增加成年海马和皮质神经发生以及逆转海马、杏仁核和皮质中的神经元成熟。然而，由于大多数先前的研究使用了啮齿动物模型，因此尚不清楚这些 FLX 诱导的变化是否发生在灵长类动物的大脑中。为了评估 FLX 在灵长类动物大脑中的作用，我们使用免疫组织化学方法评估了慢性 FLX 治疗（3mg/kg/天，持续 4 周）后成年狨猴大脑中的神经发生和神经元成熟标志物的表达（每组 n=3）。我们发现 FLX 处理的狨猴海马齿状回中的双皮质素和钙视网膜蛋白表达增加，这些标志物表明不成熟神经元。此外，FLX 治疗减少了海马中具有周细胞网络的神经元的表达和数量，这表明成熟的快速放电中间神经元，但在杏仁核或大脑皮质中没有。我们还发现 FLX 治疗增加了皮质中间神经元的生成；然而，在 FLX 处理的狨猴中未观察到成年海马神经发生的显著上调。这些结果表明，海马神经元的去成熟和皮质神经发生的增加可能在 FLX 诱导的作用和/或副作用中起作用。我们的结果与先前的研究结果一致，表明 FLX 处理的啮齿动物中存在海马去成熟和皮质神经发生增加。相比之下，FLX 并未影响杏仁核和大脑皮质中海马神经发生或中间神经元的去成熟。
