Sonic hedgehog maintains cellular and neurochemical homeostasis in the adult nigrostriatal circuit.
Sonic hedgehog maintains cellular and neurochemical homeostasis in the adult nigrostriatal circuit.
复制标题
DOI：
10.1016/j.neuron.2012.05.018
复制
发表时间：
2012-07-26
期刊：
影响因子：
16.2
通讯作者：
Kottmann AH
中科院分区：
文献类型：
--
作者：
Gonzalez-Reyes LE;Verbitsky M;Blesa J;Jackson-Lewis V;Paredes D;Tillack K;Phani S;Kramer ER;Przedborski S;Kottmann AH
非细胞自主过程被认为在健康和患病大脑的细胞维持中发挥关键作用，但机制细节仍不清楚。我们报告说，中断的非细胞自主模式的音刺猬（Shh）信号来源于多巴胺能神经元导致进行性，成年发病变性的多巴胺能，胆碱能和快速尖峰GABA能神经元的中纹状体电路，胆碱能和多巴胺能神经传递的不平衡，和运动缺陷联想到帕金森氏病。可变Shh信号传导导致纹状体中毒蕈碱自身受体和GDNF表达的分级抑制。反过来，从纹状体胆碱能神经元发出的分级信号并参与经典GDNF受体Ret抑制多巴胺能神经元中的Shh表达。因此，我们发现了一种新的机制，神经元亚型特异性和互惠通信是必不可少的神经化学和结构的稳态在黑质纹状体电路。这些结果提供了对可能在神经退行性疾病如帕金森病中起作用的非细胞自主过程的综合见解。
Non cell-autonomous processes are thought to play critical roles in the cellular maintenance of the healthy and diseased brain but mechanistic details remain unclear. We report that the interruption of a non-cell autonomous mode of sonic hedgehog (Shh) signaling originating from dopaminergic neurons causes progressive, adult-onset degeneration of dopaminergic, cholinergic, and fast spiking GABAergic neurons of the mesostriatal circuit, imbalance of cholinergic and dopaminergic neurotransmission, and motor deficits reminiscent of Parkinson’s disease. Variable Shh signaling results in graded inhibition of muscarinic auto-receptor- and GDNF- expression in the striatum. Reciprocally, graded signals that emanate from striatal cholinergic neurons and engage the canonical GDNF receptor Ret inhibit Shh expression in dopaminergic neurons. Thus, we discovered a novel mechanism for neuronal subtype specific and reciprocal communication that is essential for neurochemical and structural homeostasis in the nigrostriatal circuit. These results provide integrative insights into non cell-autonomous processes likely at play in neurodegenerative conditions such as Parkinson’s disease.
登录
查看更多内容
影响因子：
4.1
作者：
DeLong, Mahlon;Wichmann, Thomas
通讯作者：
Wichmann, Thomas
影响因子：
25
作者：
Ding, Jun;Guzman, Jaime N.;Surmeier, D. James
通讯作者：
Surmeier, D. James
影响因子：
5.3
作者：
Tsuboi, K;Shults, CW
通讯作者：
Shults, CW
影响因子：
56.9
作者：
LIN, LFH;DOHERTY, DH;COLLINS, F
通讯作者：
COLLINS, F
影响因子：
1.7
作者：
Loulier, K;Ruat, M;Traiffort, E
通讯作者：
Traiffort, E