中央脑深部刺激对啮齿动物癫痫模型纹状体谷氨酸和GABA的影响。

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-07-24 DOI:10.1016/j.expneurol.2025.115394

Rafi Matin , Kristina Zhang , Flavia Venetucci Gouveia , George M. Ibrahim

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引用次数: 0

摘要

背景：丘脑中央核深部脑刺激（DBS）是治疗耐药癫痫的一种很有前途的方法。CM-DBS的抗癫痫作用与丘脑纹状体投射有关，然而，在啮齿动物癫痫模型中，刺激纹状体的神经化学作用仍未被探索。目的：研究CM-DBS对健康和癫痫模型小鼠丘脑纹状体回路中谷氨酸和GABA信号通路的急性神经化学作用。方法：C57BL/6 J健康对照（n = 18）和Cntnap2KO癫痫小鼠模型（n = 18）行CM-DBS植入手术。DBS-ON组小鼠接受刺激，DBS-OFF组小鼠接受手术但不接受刺激。刺激实验结束后，立即恢复大脑，并从丘脑纹状体网络区域（即丘脑，尾状壳核）和单独的边缘网络节点（即杏仁核，海马，腹侧白球）中解剖组织。最后，采用液相色谱-串联质谱法定量脑组织样品中谷氨酸和GABA的浓度。研究了DBS对局部神经递质水平和神经递质网络的影响。结果：在基线时，与健康对照组相比，Cntnap2KO小鼠纹状体谷氨酸/GABA比率较低。CM-DBS后，两种小鼠纹状体内谷氨酸水平均升高。此外，CM-DBS改变了C57BL/6 J小鼠纹状体网络内的神经递质关系，选择性地降低了GABA-GABA和谷氨酸- gaba的相关性。结论：CM-DBS诱导谷氨酸和GABA水平的区域和品系依赖性变化，影响神经递质网络动力学。这些发现强调了CM-DBS后丘脑纹状体投射的潜在神经化学变化。

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Effects of centromedian thalamic deep brain stimulation on striatal glutamate and GABA in a rodent model of epilepsy

Background

Deep brain stimulation (DBS) of the centromedian nucleus of thalamus (CM) represents a promising treatment for drug-resistant epilepsy. The anti-seizure effects of CM-DBS have been linked to thalamostriatal projections, however, the neurochemical effects of stimulation on the striatum remain unexplored.

Objective

This study aimed to characterize the acute neurochemical effects of CM-DBS on glutamate and GABA signaling within thalamostriatal circuits in healthy and epileptic mouse models.

Methods

C57BL/6 J healthy controls (n = 18) and the Cntnap2KO mouse model of epilepsy (n = 18) underwent surgery for CM-DBS implants. Mice in the DBS-ON group received stimulation, while mice in the DBS-OFF group underwent surgery but did not receive stimulation. Immediately after stimulation experiments, the brains were recovered and tissue was dissected from regions within the thalamostriatal network (i.e. thalamus, caudate putamen) and nodes from a separate limbic network (i.e. amygdala, hippocampus, ventral pallidum). Finally, liquid chromatography with tandem mass spectrometry was used to quantify glutamate and GABA concentrations in brain tissue samples. The effects of DBS on regional neurotransmitter levels and neurotransmitter networks were studied.

Results

At baseline, the striatal Glutamate/GABA ratio was lower in Cntnap2KO mice compared to healthy controls. Following CM-DBS, glutamate levels increased within the striatum in both mouse strains. Furthermore, CM-DBS altered neurotransmitter relationships within striatal networks and selectively reduced GABA-GABA and glutamate-GABA correlations in C57BL/6 J mice.

Conclusion

CM-DBS induced region- and strain-dependent changes in glutamate and GABA levels with effects on neurotransmitter network dynamics. These findings highlight potential neurochemical changes in thalamostriatal projections following CM-DBS.

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.