局部雌激素合成调控小脑皮层内平行纤维-浦肯野细胞神经传递。
Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex.
机构信息
Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota.
State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Nanjing, China.
出版信息
Endocrinology. 2018 Mar 1;159(3):1328-1338. doi: 10.1210/en.2018-00039.
Estrogens affect cerebellar activity and cerebellum-based behaviors. Within the adult rodent cerebellum, the best-characterized action of estradiol is to enhance glutamatergic signaling. However, the mechanisms by which estradiol promotes glutamatergic neurotransmission remain unknown. Within the mouse cerebellum, we found that estrogen receptor activation of metabotropic glutamate receptor type 1a strongly enhances neurotransmission at the parallel fiber-Purkinje cell synapse. The blockade of local estrogen synthesis within the cerebellum results in a diminution of glutamatergic neurotransmission. Correspondingly, decreased estrogen availability via gonadectomy or blockade of aromatase activity negatively affects locomotor performance. These data indicate that locally derived, and not just gonad-derived, estrogens affect cerebellar physiology and function. In addition, estrogens were found to facilitate parallel fiber-Purkinje cell synaptic transmission in both sexes. As such, the actions of estradiol to support cerebellar neurotransmission and cerebellum-based behaviors might be fundamental to understanding the normal processing of activity within the cerebellar cortex.
雌激素会影响小脑活动和基于小脑的行为。在成年啮齿动物的小脑内，雌二醇作用最明显的特征是增强谷氨酸能信号传递。然而，雌激素促进谷氨酸能神经传递的机制尚不清楚。在小鼠小脑内，我们发现，代谢型谷氨酸受体 1a 的雌激素受体激活强烈增强了平行纤维-浦肯野细胞突触的神经传递。小脑内局部雌激素合成的阻断会导致谷氨酸能神经传递减少。相应地，通过去势或芳香酶活性阻断导致雌激素可用性降低，会对运动表现产生负面影响。这些数据表明，源自局部而非性腺的雌激素会影响小脑的生理和功能。此外，还发现雌激素可促进两性的平行纤维-浦肯野细胞突触传递。因此，雌二醇支持小脑神经传递和基于小脑的行为的作用可能对理解小脑皮层内活动的正常处理至关重要。
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