Loss of estrogen-related receptor alpha disrupts ventral-striatal synaptic function in female mice.
Loss of estrogen-related receptor alpha disrupts ventral-striatal synaptic function in female mice.
复制标题
DOI：
10.1016/j.neuroscience.2016.04.054
复制
发表时间：
2016-08-04
期刊：
影响因子：
3.3
通讯作者：
Cui H
中科院分区：
文献类型：
--
作者：
De Jesús-Cortés H;Lu Y;Anderson RM;Khan MZ;Nath V;McDaniel L;Lutter M;Radley JJ;Pieper AA;Cui H
进食障碍（Eating Disorders，ED）是一种以高发病率和高死亡率为特征的精神疾病，包括神经性厌食症、神经性贪食症和暴食症。虽然一些研究已经确定了ED患者的神经功能缺损，但对潜在功能障碍的细胞和分子基础仍然知之甚少。我们以前确定了一种罕见的错义突变的转录因子雌激素相关受体α（ESRRA）与发展的ED。由于腹侧纹状体信号与被认为是ED基础的奖励和动机电路有关，我们对Esrra缺失小鼠的腹侧纹状体突触进行了功能和结构分析。Esrra基因敲除的雌性小鼠（而非雄性小鼠）在腹侧纹状体中的中型棘神经元（MSN）上表现出改变的微型兴奋性突触后电流，包括频率增加、振幅增加和成对脉冲比降低。这些电生理措施与腹侧纹状体中MSN突触的结构和分子变化相关，包括更少的突触前神经元能囊泡和增强的GluR1功能。因此，需要神经元Esrra来维持腹侧纹状体中的正常突触功能，这可以提供对在Esrra缺失小鼠中观察到的行为缺陷的机制见解。
Eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge-ED, are mental illnesses characterized by high morbidity and mortality. While several studies have identified neural deficits in patients with EDs, the cellular and molecular basis of the underlying dysfunction has remained poorly understood. We previously identified a rare missense mutation in the transcription factor estrogen-related receptor alpha (ESRRA) associated with development of EDs. Because ventral-striatal signaling is related to the reward and motivation circuitry thought to underlie EDs, we performed functional and structural analysis of ventral-striatal synapses in Esrra-null mice. Esrra-null female, but not male, mice exhibit altered miniature excitatory postsynaptic currents on medium spiny neurons (MSNs) in the ventral striatum, including increased frequency, increased amplitude, and decreased paired pulse ratio. These electrophysiological measures are associated with structural and molecular changes in synapses of MSNs in the ventral striatum, including fewer pre-synaptic glutamatergic vesicles and enhanced GluR1 function. Neuronal Esrra is thus required for maintaining normal synaptic function in the ventral striatum, which may offer mechanistic insights into the behavioral deficits observed in Esrra-null mice.
登录
查看更多内容
影响因子：
25
作者：
Kreple, Collin J.;Lu, Yuan;Wemmie, John A.
通讯作者：
Wemmie, John A.
影响因子：
2.5
作者：
Radley, Jason J.;Rocher, Anne B.;Hof, Patrick R.
通讯作者：
Hof, Patrick R.
影响因子：
14.8
作者：
Rodriguez, Alfredo;Ehlenberger, Douglas B.;Wearne, Susan L.
通讯作者：
Wearne, Susan L.
影响因子：
5.3
作者：
Anderson, Rachel M.;Birnie, Andrew K.;Radley, Jason J.
通讯作者：
Radley, Jason J.
影响因子：
5.1
作者：
Wang, JQ;Arora, A;Mao, LM
通讯作者：
Mao, LM