灵长类背外侧前额叶皮层 GABA 能中间神经元上的β1-肾上腺素受体表达:在压力诱导的认知功能障碍中的潜在作用

IF 4.3 2区 医学 Q1 NEUROSCIENCES Neurobiology of Stress Pub Date : 2024-03-15 DOI:10.1016/j.ynstr.2024.100628
M.K.P. Joyce, S. Yang, K. Morin, A. Duque, J. Arellano, D. Datta, M. Wang, A.F.T. Arnsten
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引用次数: 0

摘要

无法控制的压力会损害工作记忆,并降低背外侧前额叶皮层(dlPFC)"延迟细胞 "的发射,这涉及到高水平的去甲肾上腺素和多巴胺释放。以前的研究主要关注儿茶酚胺对前额叶皮质锥体细胞的作用,但抑制性中间神经元也可能起作用。本研究将免疫组化、多尺度显微镜、离子渗透生理学和行为分析结合起来,研究了β1-去甲肾上腺素能受体(β1-ARs)对第III层dlPFC抑制性神经元的影响。我们发现β1-AR在不同类别的抑制性神经元上都有很强的表达,这些抑制性神经元由钙结合蛋白钙宾蛋白(CB)、钙视蛋白(CR)和钙旁蛋白(PV)标记。免疫电镜证实,β1-AR 在 PV 表达树突的质膜上表达。在生理记录中,PV 中间神经元可被识别为快速尖峰(FS),因此在猕猴执行工作记忆任务时对其进行了研究。对β1-AR激动剂进行离子注入会产生混合效应,增加一个子集的点燃,减少其他子集的点燃,这可能反映了整个微电路点燃的丧失。这种整体发射损失可能是应激时工作记忆受损的原因之一,因为使用选择性β1-AR拮抗剂奈必洛尔进行预处理可防止应激引起的工作记忆缺陷。因此,选择性β1-AR拮抗剂可能有助于治疗应激相关疾病。
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β1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction

Uncontrollable stress exposure impairs working memory and reduces the firing of dorsolateral prefrontal cortex (dlPFC) “Delay cells”, involving high levels of norepinephrine and dopamine release. Previous work has focused on catecholamine actions on dlPFC pyramidal cells, but inhibitory interneurons may contribute as well. The current study combined immunohistochemistry and multi-scale microscopy with iontophoretic physiology and behavioral analyses to examine the effects of beta1-noradrenergic receptors (β1-ARs) on inhibitory neurons in layer III dlPFC. We found β1-AR robustly expressed on different classes of inhibitory neurons labeled by the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV). Immunoelectron microscopy confirmed β1-AR expression on the plasma membrane of PV-expressing dendrites. PV interneurons can be identified as fast-spiking (FS) in physiological recordings, and thus were studied in macaques performing a working memory task. Iontophoresis of a β1-AR agonist had a mixed effect, increasing the firing of a subset and decreasing the firing of others, likely reflecting loss of firing of the entire microcircuit. This loss of overall firing likely contributes to impaired working memory during stress, as pretreatment with the selective β1-AR antagonist, nebivolol, prevented stress-induced working memory deficits. Thus, selective β1-AR antagonists may be helpful in treating stress-related disorders.

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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
期刊最新文献
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