小脑源性神经营养因子-TrkB缺陷与星状突变小鼠眨眼条件反射受损相关。
Cerebellar brain-derived neurotrophic factor-TrkB defect associated with impairment of eyeblink conditioning in Stargazer mutant mice.
作者信息
Qiao X, Chen L, Gao H, Bao S, Hefti F, Thompson R F, Knusel B
机构信息
Program for Neural, Informational, and Behavioral Sciences, University of Southern California, Los Angeles, California 90089, USA.
出版信息
J Neurosci. 1998 Sep 1;18(17):6990-9. doi: 10.1523/JNEUROSCI.18-17-06990.1998.
Abstract
In the spontaneous ataxic mutant mouse stargazer, there is a selective reduction of brain-derived neurotrophic factor (BDNF) mRNA expression in the cerebellum. BDNF protein levels in the cerebellum are reduced by 70%. Despite normal levels of full-length and truncated TrkB receptor, constitutive and neurotrophin-4/5-induced tyrosine phosphorylation was significantly reduced in several signal transduction molecules, including phospholipase-Cgamma1, erk1, and erk2. Morphological examination revealed an increased number of external granule cells at postnatal day 15 and the presence of abnormal neurons resembling immature granule cells in the adult. These abnormalities are associated with a severe impairment in the acquisition of classical eyeblink conditioning, indicating cerebellar malfunction. Our data suggest that normal BDNF expression and TrkB signal transduction in the cerebellum are necessary for learning and plasticity in this model.
摘要
在自发性共济失调突变小鼠“凝视者”中，小脑内脑源性神经营养因子（BDNF）mRNA表达有选择性降低。小脑中BDNF蛋白水平降低了70%。尽管全长和截短的TrkB受体水平正常，但包括磷脂酶Cγ1、erk1和erk2在内的几种信号转导分子中的组成型和神经营养因子4/5诱导的酪氨酸磷酸化显著降低。形态学检查显示，出生后第15天外部颗粒细胞数量增加，且成年小鼠中存在类似未成熟颗粒细胞的异常神经元。这些异常与经典眨眼条件反射习得的严重受损有关，表明小脑功能失调。我们的数据表明，小脑中正常的BDNF表达和TrkB信号转导对于该模型中的学习和可塑性是必需的。
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