Neuropsychopharmacology ：一种抗抑郁药或可治疗大脑皮质损伤

日本医学专家日前在美国期刊《神经心理药物学》上报告说，他们给一些正常的成年实验鼠使用一种抗抑郁药，成功使其抑制性神经元的数量增加。

这一发现将有助于研究如何防止抑制性神经元数量减少，为防治与此相关的大脑皮质损伤提供新方法。

日本藤田保健卫生大学综合医学研究所的宫川刚教授和同事，连续3周给一些实验鼠喂食抗抑郁药氟西汀，给对照组实验鼠喂食生理盐水。3周后，“氟西汀组”实验鼠的大脑皮质几乎所有区域都出现神经祖细胞增加现象。由这些神经祖细胞分化而成的神经细胞中，约80%为抑制性神经元。与喂食生理盐水的对照组相比，“氟西汀组”实验鼠的新生抑制性神经元数量达到前者的近20倍。

另外，研究人员还通过实验证明，这些新生的抑制性神经元能抑制因脑缺血引起的细胞死亡。

doi: 10.1038/npp.2013.2
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Fluoxetine-Induced Cortical Adult Neurogenesis

Koji Ohira1,2, Rika Takeuchi1,2, Hirotaka Shoji1,2 and Tsuyoshi Miyakawa1,2,3

Adult neurogenesis in the hippocampal subgranular zone (SGZ) and the anterior subventricular zone (SVZ) is regulated by multiple factors, including neurotransmitters, hormones, stress, aging, voluntary exercise, environmental enrichment, learning, and ischemia. Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) modulates adult neurogenesis in the SGZ, the neuronal area that is hypothesized to mediate the antidepressant effects of these substances. Layer 1 inhibitory neuron progenitor cells (L1-INP cells) were recently identified in the adult cortex, but it remains unclear what factors other than ischemia affect the neurogenesis of L1-INP cells. Here, we show that chronic treatment with an SSRI, fluoxetine (FLX), stimulated the neurogenesis of gamma-aminobutyric acid (GABA)ergic interneurons from L1-INP cells in the cortex of adult mice. Immunofluorescence and genetic analyses revealed that FLX treatment increased the number of L1-INP cells in all examined cortical regions in a dose-dependent manner. Furthermore, enhanced Venus reporter expression driven by the synapsin I promoter demonstrated that GABAergic interneurons were derived from retrovirally labeled L1-INP cells. In order to assess if these new GABAergic interneurons possess physiological function, we examined the their effect on apoptosis surrounding areas following ischemia. Intriguingly, the number of neurons expressing the apoptotic marker, active caspase-3, was significantly lower in adult mice pretreated with FLX. Our findings indicate that FLX stimulates the neurogenesis of cortical GABAergic interneurons, which might have, at least, some functions, including a suppressive effect on apoptosis induced by ischemia.