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神经发生和星形胶质细胞发生对成年猫单侧前庭神经切断术后前庭功能恢复的贡献:细胞和行为学证据。

Neurogenesis and astrogenesis contribution to recovery of vestibular functions in the adult cat following unilateral vestibular neurectomy: cellular and behavioral evidence.

机构信息

UMR 6149 Neurosciences Intégratives et Adaptatives, Pôle 3C, Comportement, Cerveau, Cognition, Centre de St Charles, Case B-3 Place Victor Hugo, 13331 Marseille Cedex 3-France.

出版信息

Neuroscience. 2009 Dec 29;164(4):1444-56. doi: 10.1016/j.neuroscience.2009.09.048. Epub 2009 Sep 25.

Abstract

In physiological conditions, neurogenesis occurs in restricted regions of the adult mammalian brain, giving rise to integrated neurons into functional networks. In pathological or postlesional conditions neurogenesis and astrogenesis can also occur, as demonstrated in the deafferented vestibular nuclei after immediate unilateral vestibular neurectomy (UVN) in the adult cat. To determine whether the reactive cell proliferation and beyond neurogenesis and astrogenesis following UVN plays a functional role in the vestibular functions recovery, we examined the effects of an antimitotic drug: the cytosine-beta-d arabinofuranoside (AraC), infused in the fourth ventricle after UVN. Plasticity mechanisms were evidenced at the immunohistochemical level with bromodeoxyuridine, GAD67 and glial fibrillary acidic protein (GFAP) stainings. Consequences of immediate or delayed AraC infusion on the behavioral recovery processes were evaluated with oculomotor and posturo-locomotor tests. We reported that after UVN, immediate AraC infusion blocked the cell proliferation and decreased the number of GFAP-immunoreactive cells and GABAergic neurons observed in the vestibular nuclei of neurectomized cats. At the behavioral level, after UVN and immediate AraC infusion the time course of posturo-locomotor function recovery was drastically delayed, and no alteration of the horizontal spontaneous nystagmus was observed. In contrast, an infusion of AraC beginning 3 weeks after UVN had no influence neither on the time course of the behavioral recovery, nor on the reactive cell proliferation and its differentiation. We conclude that the first 3 weeks after UVN represent a possible critical period in which important neuroplasticity mechanisms take place for promoting vestibular function recovery: reactive neurogenesis and astrogenesis might contribute highly to vestibular compensation in the adult cat.

摘要

在生理条件下,神经发生发生在成年哺乳动物大脑的受限区域,产生整合到功能网络中的神经元。在病理或损伤后条件下,神经发生和星形胶质细胞发生也可能发生,如在成年猫单侧前庭神经切断术后(UVN)立即去传入的前庭核中所证明的那样。为了确定 UVN 后反应性细胞增殖以及神经发生和星形胶质细胞发生是否在前庭功能恢复中发挥功能作用,我们检查了抗有丝分裂药物的影响:胞嘧啶-β-D-阿拉伯呋喃糖苷(AraC),在 UVN 后注入第四脑室。用溴脱氧尿苷、GAD67 和神经胶质纤维酸性蛋白(GFAP)染色在免疫组织化学水平上证明了可塑性机制。用眼动和姿势运动测试评估了立即或延迟 AraC 输注对行为恢复过程的影响。我们报道,在 UVN 后,立即 AraC 输注阻断了细胞增殖,并减少了在去传入的猫前庭核中观察到的 GFAP 免疫反应性细胞和 GABA 能神经元的数量。在行为水平上,在 UVN 和立即 AraC 输注后,姿势运动功能恢复的时间过程明显延迟,并且没有观察到水平自发眼球震颤的改变。相比之下,在 UVN 后 3 周开始的 AraC 输注对行为恢复的时间过程没有影响,也没有对反应性细胞增殖及其分化产生影响。我们得出结论,在 UVN 后 3 周内代表了一个可能的关键时期,在此期间发生了重要的神经可塑性机制,以促进前庭功能恢复:反应性神经发生和星形胶质细胞发生可能对成年猫的前庭代偿做出高度贡献。

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