Allami Pantea, Yazdanpanah Niloufar, Rezaei Nima
Student's Scientific Research Center, School of Medicine, 48439 Tehran University of Medical Sciences , Pour Sina St, Tehran 1416634793, Iran.
Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Children's Medical Center Hospital, Dr. Qarib St, Keshavarz Blvd, Tehran 14194, Iran.
Rev Neurosci. 2025 Jan 24. doi: 10.1515/revneuro-2024-0153.
Fast spiking parvalbumin (PV) interneuron is an inhibitory gamma-aminobutyric acid (GABA)ergic interneuron diffused in different brain networks, including the cortex and hippocampus. As a key component of brain networks, PV interneurons collaborate in fundamental brain functions such as learning and memory by regulating excitation and inhibition (E/I) balance and generating gamma oscillations. The unique characteristics of PV interneurons, like their high metabolic demands and long branching axons, make them too vulnerable to stressors. Neuroinflammation is one of the most significant stressors that have an adverse, long-lasting impact on PV interneurons. Neuroinflammation affects PV interneurons through specialized inflammatory pathways triggered by cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6). The crucial cells in neuroinflammation, microglia, also play a significant role. The destructive effect of inflammation on PV interneurons can have comprehensive effects and cause neurological disorders such as schizophrenia, Alzheimer's disease (AD), autism spectrum disorder (ASD), and bipolar disorder. In this article, we provide a comprehensive review of mechanisms in which neuroinflammation leads to PV interneuron hypofunction in these diseases. The integrated knowledge about the role of PV interneurons in cognitive networks of the brain and mechanisms involved in PV interneuron impairment in the pathology of these diseases can help us with better therapeutic interventions.
快速放电小白蛋白（PV）中间神经元是一种抑制性γ-氨基丁酸（GABA）能中间神经元，广泛分布于包括皮层和海马体在内的不同脑网络中。作为脑网络的关键组成部分，PV中间神经元通过调节兴奋与抑制（E/I）平衡并产生γ振荡，在学习和记忆等基本脑功能中协同发挥作用。PV中间神经元的独特特性，如其高代谢需求和长分支轴突，使其极易受到应激源的影响。神经炎症是对PV中间神经元产生不利且持久影响的最重要应激源之一。神经炎症通过肿瘤坏死因子（TNF）和白细胞介素6（IL-6）等细胞因子触发的特定炎症途径影响PV中间神经元。神经炎症中的关键细胞小胶质细胞也发挥着重要作用。炎症对PV中间神经元的破坏作用可能产生全面影响，并导致精神分裂症、阿尔茨海默病（AD）、自闭症谱系障碍（ASD）和双相情感障碍等神经疾病。在本文中，我们全面综述了神经炎症在这些疾病中导致PV中间神经元功能减退的机制。关于PV中间神经元在脑认知网络中的作用以及这些疾病病理过程中PV中间神经元损伤所涉及机制的综合知识有助于我们进行更好的治疗干预。
