Luk K C, Sadikot A F
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, H3A 2B4, Montreal, Canada.
Neuroscience. 2001;104(1):93-103. doi: 10.1016/s0306-4522(01)00038-0.
Amino-acid neurotransmitters regulate a wide variety of developmental processes in the mammalian CNS including neurogenesis, cell migration, and apoptosis. In order to investigate the role of GABA in early development of forebrain interneurons, we determined the survival of parvalbumin-immunoreactive GABAergic interneurons in the adult rat striatum following prenatal exposure to either GABA(A) receptor agonist or antagonist. Unbiased stereology was used to quantify parvalbumin-immunoreactive neuron number in the neostriatum of adult rats exposed to the drugs in utero, and the results were compared to pair-fed or vehicle controls. Embryos were exposed to the GABA(A) antagonist (bicuculline) or agonist (muscimol) during previously defined proliferative or post-proliferative periods for parvalbumin-immunoreactive interneurons. Unbiased stereology using the optical fractionator was used to estimate the total number of parvalbumin-immunoreactive neurons in neostriatum of experimental and control rats. No significant alteration in parvalbumin-immunoreactive neuron number was observed in rats treated with either bicuculline (1 or 2mg/kg/day) or muscimol (1mg/kg/day) during the proliferative phase. Administration of bicuculline during the post-proliferative phase significantly reduced parvalbumin-immunoreactive neuron number in the neostriatum. A concomitant decrease in neostriatal volume was also observed, suggesting that the effect is not restricted to parvalbumin-immunoreactive interneurons. Positional analysis revealed loss of normal regional distribution gradients for parvalbumin-immunoreactive neurons in neostriatum of rats exposed to bicuculline in the embryonic post-proliferative phase. This data collectively suggests that GABA promotes survival but not proliferation of parvalbumin-immunoreactive progenitors. GABA may also promote migration of subpopulations of interneurons that ultimately populate the ventral telencephalon.
氨基酸神经递质调节哺乳动物中枢神经系统中广泛的发育过程，包括神经发生、细胞迁移和细胞凋亡。为了研究γ-氨基丁酸（GABA）在前脑中间神经元早期发育中的作用，我们测定了成年大鼠纹状体中钙结合蛋白免疫反应性GABA能中间神经元在产前暴露于GABA(A)受体激动剂或拮抗剂后的存活率。采用无偏立体学方法对子宫内暴露于药物的成年大鼠新纹状体中钙结合蛋白免疫反应性神经元数量进行量化，并将结果与配对喂食或溶剂对照组进行比较。在先前确定的钙结合蛋白免疫反应性中间神经元增殖期或增殖后期，胚胎暴露于GABA(A)拮抗剂（荷包牡丹碱）或激动剂（蝇蕈醇）。使用光学分割器的无偏立体学方法用于估计实验大鼠和对照大鼠新纹状体中钙结合蛋白免疫反应性神经元的总数。在增殖期用荷包牡丹碱（1或2mg/kg/天）或蝇蕈醇（1mg/kg/天）处理的大鼠中，未观察到钙结合蛋白免疫反应性神经元数量有显著变化。在增殖后期给予荷包牡丹碱显著减少了新纹状体中钙结合蛋白免疫反应性神经元的数量。同时还观察到新纹状体体积减小，这表明该效应不限于钙结合蛋白免疫反应性中间神经元。位置分析显示，在胚胎增殖后期暴露于荷包牡丹碱的大鼠新纹状体中，钙结合蛋白免疫反应性神经元的正常区域分布梯度丧失。这些数据共同表明，GABA促进钙结合蛋白免疫反应性祖细胞的存活但不促进其增殖。GABA还可能促进最终定居于腹侧端脑的中间神经元亚群的迁移。
