Astrocytes play a critical role in mediating the effect of acute ethanol on central amygdala glutamatergic transmission.
Astrocytes play a critical role in mediating the effect of acute ethanol on central amygdala glutamatergic transmission.
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DOI：
10.1016/j.neuropharm.2021.108918
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发表时间：
2022-03-01
影响因子：
4.7
通讯作者：
Silberman Y
中科院分区：
文献类型：
--
作者：
Melkumyan M;Snyder AE;Bingaman SS;Arnold AC;Silberman Y
杏仁核中央 (CeA) 与酒精使用障碍的许多方面都有密切关系。乙醇 (EtOH) 已被证明可以调节 CeA 横向细分中的谷氨酸能传递，然而，这种调节的确切机制仍不清楚。乙醇暴露与脑胶质细胞中促炎细胞因子的增加有关，并且先前已证明抑制神经免疫细胞（小胶质细胞和星形胶质细胞）可以减少动物模型中乙醇的饮用。由于神经免疫激活似乎与 EtOH 的许多作用有关，因此我们假设急性 EtOH 暴露将通过调节神经免疫细胞来增加 CeA 中的兴奋性谷氨酸能传递。利用离体脑切片全细胞膜片钳电生理学，发现生理相关浓度的 EtOH (20mM) 显着增加 CeA 中的突触前谷氨酸能传递。星形胶质细胞功能的药理学和化学遗传学抑制显着降低了 EtOH 调节 CeA 谷氨酸传递的能力，而对小胶质细胞抑制的影响最小。这一发现促使更多的研究探讨通过脂多糖 (LPS) 直接激活神经免疫是否可能导致 CeA 中谷氨酸传递的增加。研究发现，LPS 对谷氨酸能传递的调节受到小胶质细胞激活的限制，并且需要星形胶质细胞信号传导。综上所述，这些结果支持了这样的假设：急性乙醇通过星形胶质细胞介导的机制增强横向 CeA 谷氨酸传递。
The Central Amygdala (CeA) has been heavily implicated in many aspects of alcohol use disorder. Ethanol (EtOH) has been shown to modulate glutamatergic transmission in the lateral subdivision of the CeA, however, the exact mechanism of this modulation is still unclear. EtOH exposure is associated with increased pro-inflammatory cytokines in the CeA, and inhibition of neuroimmune cells (microglia and astrocytes) has previously been shown to reduce EtOH drinking in animal models. Since neuroimmune activation seems to be involved in many of the effects of EtOH, we hypothesized that acute EtOH exposure will increase excitatory glutamatergic transmission in the CeA via modulation of neuroimmune cells. Using ex vivo brain slice whole-cell patch clamp electrophysiology, it was found that a physiologically relevant concentration of EtOH (20mM) significantly increased presynaptic glutamatergic transmission in the CeA. Pharmacologic and chemogenetic inhibition of astrocyte function significantly reduced the ability of EtOH to modulate CeA glutamatergic transmission with minimal impact of microglia inhibition. This finding prompted additional studies examining whether direct neuroimmune activation through lipopolysaccharide (LPS) might lead to an increase in the glutamatergic transmission in the CeA. It was found that LPS modulation of glutamatergic transmission was limited by microglia activation and required astrocyte signaling. Taken together these results support the hypothesis that acute EtOH enhances lateral CeA glutamatergic transmission through an astrocyte mediated mechanism.
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影响因子：
4.3
作者：
Cruz MT;Bajo M;Maragnoli ME;Tabakoff B;Siggins GR;Roberto M
通讯作者：
Roberto M
影响因子：
8.2
作者：
Gilpin, Nicholas W.;Roberto, Marisa
通讯作者：
Roberto, Marisa
影响因子：
7.6
作者：
Griffin, William C., III;Haun, Harold L.;Becker, Howard C.
通讯作者：
Becker, Howard C.
影响因子：
5.3
作者：
Kayyal, Haneen;Yiannakas, Adonis;Rosenblum, Kobi
通讯作者：
Rosenblum, Kobi
DOI：
10.1073/pnas.0802302105
发表时间：
2008-06-17
影响因子：
11.1
作者：
Bajo, Michal;Cruz, Maureen T.;Roberto, Marisa
通讯作者：
Roberto, Marisa