Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
Department of Rehabilitation Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China.
Neurochem Int. 2024 May;175:105720. doi: 10.1016/j.neuint.2024.105720. Epub 2024 Mar 6.
The anteroventral bed nucleus of stria terminalis (avBNST) is a key brain region which involves negative emotional states, such as anxiety. The most neurons in the avBNST are GABAergic, and it sends GABAergic projections to the ventral tegmental area (VTA) and the dorsal raphe nucleus (DRN), respectively. The VTA and DRN contain dopaminergic and serotonergic cell groups in the midbrain which regulate anxiety-like behaviors. However, it is unclear the role of GABAergic projections from the avBNST to the VTA and the DRN in the regulation of anxiety-like behaviors, particularly in Parkinson's disease (PD)-related anxiety. In the present study, unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, and decreased level of dopamine (DA) in the basolateral amygdala (BLA). Chemogenetic activation of avBNST-VTA or avBNST-DRN pathway induced anxiety-like behaviors and decreased DA or 5-HT release in the BLA in sham and 6-OHDA rats, while inhibition of avBNST-VTA or avBNST-DRN pathway produced anxiolytic-like effects and increased level of DA or 5-HT in the BLA. These findings suggest that avBNST inhibitory projections directly regulate dopaminergic neurons in the VTA and serotonergic neurons in the DRN, and the avBNST-VTA and avBNST-DRN pathways respectively exert impacts on PD-related anxiety-like behaviors.
终纹床核腹前核(avBNST)是涉及负性情绪状态(如焦虑)的关键脑区。avBNST 中的大多数神经元为 GABA 能神经元,它们分别向腹侧被盖区(VTA)和中缝背核(DRN)投射 GABA 能神经纤维。VTA 和 DRN 中含有中脑的多巴胺能和 5-羟色胺能神经元群,它们调节焦虑样行为。然而,avBNST 投射到 VTA 和 DRN 的 GABA 能神经纤维在调节焦虑样行为中的作用尚不清楚,特别是在帕金森病(PD)相关焦虑中。在本研究中,单侧 6-羟多巴胺(6-OHDA)损毁大鼠黑质致密部诱导出焦虑样行为,并降低了外侧杏仁核(BLA)中的多巴胺(DA)水平。化学遗传学激活 avBNST-VTA 或 avBNST-DRN 通路在假手术和 6-OHDA 大鼠中诱导出焦虑样行为,并降低了 BLA 中的 DA 或 5-HT 释放,而抑制 avBNST-VTA 或 avBNST-DRN 通路则产生抗焦虑样作用并增加了 BLA 中的 DA 或 5-HT 水平。这些发现表明,avBNST 抑制性投射直接调节 VTA 中的多巴胺能神经元和 DRN 中的 5-羟色胺能神经元,avBNST-VTA 和 avBNST-DRN 通路分别对 PD 相关的焦虑样行为产生影响。
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