Fluoxetine-induced proliferation and differentiation of neural progenitor cells isolated from rat postnatal cerebellum.
Fluoxetine-induced proliferation and differentiation of neural progenitor cells isolated from rat postnatal cerebellum.
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DOI：
10.1016/j.bcp.2008.05.014
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发表时间：
2008-08
影响因子：
5.8
通讯作者：
M. Zusso;P. Debetto;D. Guidolin;M. Barbierato;H. Manev;P. Giusti
中科院分区：
文献类型：
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作者：
M. Zusso;P. Debetto;D. Guidolin;M. Barbierato;H. Manev;P. Giusti
先前的研究表明，氟西汀（SSRI）可影响来自出生后小脑或成年海马的神经祖细胞，并刺激其增殖。在人类小脑中，小脑颗粒细胞（CGC）的增殖持续到出生后第11个月，并且可能受到母乳喂养的SSRIs的影响。目前关于氟西汀对出生后小脑神经祖细胞影响的信息有限。在这里，我们报告的特点氟西汀行动对大鼠出生后小脑神经祖细胞。RT-PCR和免疫组化显示5-羟色胺转运体（SERT）、5-HT 1A受体、色氨酸羟化酶（TPH）和5-羟色胺（5-HT）的表达。氟西汀处理的Proximal体外细胞增殖和分化增加。氟西汀、5 HT和5 HT 1A受体选择性激动剂反式-8-羟基-2-（N-正丙基-N-3′-碘-2 ′-丙烯基）氨基四氢萘（8-OH-PIPAT）的增殖作用可被5 HT 1A受体选择性拮抗剂N-[2-[4-（2-甲氧基苯基）-1-哌嗪基]乙基]-N-（2-吡啶基）环己烷甲酰胺三盐酸盐（WAY-100635）所消除。此外，氟西汀诱导cAMP反应元件结合（CREB）蛋白和细胞外信号调节蛋白激酶（ERK 1/2）的激活，这被MAP激酶激酶（MEK）的选择性抑制剂1，4-二氨基-2，3-二氰基-1，4-双（2-氨基苯硫基）丁二烯（U 0126）消除，并增加细胞周期蛋白D1的表达。WAY-100635可预防所有这些效应。总的来说，我们的研究结果表明，大鼠出生后小脑含有神经祖细胞能够增殖和分化的氟西汀暴露，可能通过激活5 HT 1A受体。这些研究结果的相关性可能SSRI对发育中的出生后/婴儿人类小脑的影响应进行探讨。
Previous studies have shown that the serotonin-reuptake inhibitor (SSRI) fluoxetine affects neural progenitors derived from postnatal cerebellum or adult hippocampus and stimulates their proliferation. In the human cerebellum, the proliferation of cerebellar granule cells (CGC) continues until the 11th postnatal month and could be influenced in infants by breastfeeding-delivered SSRIs. Current information about fluoxetine effects on postnatal cerebellar neural progenitors is limited. Here we report the characterization of fluoxetine actions on rat postnatal cerebellar neural progenitors. RT-PCR and immunostaining revealed the expression of serotonin transporter (SERT), 5HT1Areceptors, tryptophan hydroxylase (TPH), and serotonin (5HT). Protracted in vitro fluoxetine treatment increased cell proliferation and differentiation. The proliferative effects of fluoxetine, 5HT, and the selective agonist of 5HT1Areceptors trans-8-hydroxy-2-(N-n-propyl-N-3′-iodo-2′-propenyl)aminotetralin (8-OH-PIPAT) were abolished by the selective antagonist of 5HT1Areceptors, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635). Furthermore, fluoxetine-induced activation of both the cAMP-response element-binding (CREB) protein and extracellular signal-regulated protein kinases (ERK1/2), which was abolished by the selective inhibitor of MAP kinase kinase (MEK) 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), and increased cyclin D1 expression. All these effects were prevented by WAY-100635. Collectively, our results demonstrate that rat postnatal cerebellum contains neural progenitors capable of proliferating and differentiating in response to fluoxetine exposure, possibly through the activation of 5HT1Areceptors. The relevance of these findings for possible SSRI effects on the developing postnatal/infant human cerebellum should be explored.