GABAB receptors in glial cells: from physiological regulation to pathological implications

The GABAB receptor, a metabotropic receptor for the inhibitory neurotransmitter γ-aminobutyric acid, is essential for the proper functioning of inhibitory neurons. Previous studies have shown that GABAB receptors are primarily expressed at presynaptic or postsynaptic membranes of inhibitory or excitatory neurons, where they play a critical role in regulating synaptic signaling. Interestingly, a growing body of evidence indicates that GABAB receptors are also expressed in various types of glial cells and can significantly influence their functions, ultimately contributing to the regulation of multiple processes in the central nervous system. In this review, we first summarize the structure of GABAB receptors and their common downstream signaling pathways in neuronal and glial cells. We then highlight recent research progresses about how GABAB receptors in different glial cell types participate in regulating various important physiological processes, such as excitatory/inhibitory balance, synaptic pruning, and myelination. Furthermore, we provide a comprehensive overview of the significant roles played by glial GABAB receptors in the pathogenesis of neurological disorders, including epilepsy, inflammatory diseases, Alzheimer's disease, major depressive disorder, cerebrovascular diseases, and multiple sclerosis. Accumulating evidence indicates that glial GABAB receptors play a pivotal role in both health and disease, highlighting their potential as therapeutic targets for a variety of neurological conditions. By comprehensively outlining the multiple physiological and pathological processes mediated by GABAB receptors in brain glial cells, this review seeks to broaden the functional scope of glial cells and enhance the comprehension of neuron-glia crosstalk.