The role of neuroinflammation in PV interneuron impairments in brain networks; implications for cognitive disorders

Abstract

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.

Keywords: Alzheimer’s disease; autism; excitatory inhibitory balance; inflammation; microglia; schizophrenia.