Targeting Glia Cells: Novel Perspectives for the Treatment of Neuropsychiatric Diseases

Abstract

Neuropsychiatric disorders are devastating mental illnesses with a high economic burden. The additional morbidity associated with social issues that arises along with the course of these diseases increases the need for a clear understanding of their etiopathogenesis to allow an implementation of novel pharmacological strategies. Yet a poor knowledge about interactions occurring at the glia-neuron interface in health and disease still hampers innovative discoveries, despite the fact that glia cells have been long described to actively participate in the regulation of brain circuits.The purpose of this review was to collect the scattered literature on the involvement of glia cells in neuropsychiatric disorders and to describe how also these cells besides neurons might be responsive to current pharmacological interventions. We hope thereby to offer alternative approaches for investigations that may open avenues to search for new potential targets for drug discovery.

Electrophysiological properties of NG2 + cells: Matching physiological studies with gene expression profiles

“…The role of glial cells in neuropsychiatric disease is an area of increasing interest (for a comprehensive review, see (Di Benedetto and Rupprecht, 2013) and Joel Levine's chapter in this issue). Many therapeutics used to treat neuropsychiatric diseases target ion channels and neurotransmitter receptors in the brain.…”

A2A‐D2 receptor–receptor interaction modulates gliotransmitter release from striatal astrocyte processes

“…Roles for astrocytes, the most numerous cells in the nervous system, and the relevance of the neuron–astrocyte network function in neurodegenerative and neuropsychiatric disease vulnerability are being increasingly recognized (Di Benedetto and Rupprecht ; Sofroniew ; Verkhratsky and Parpura ). In particular, evidence for the presence of reactive astrocytes and neuroinflammation in the prefrontal cortex of schizophrenic patients has been reported (Catts et al .…”

Pharmacological modulation of astrocytes and the role of cell type-specific histone modifications for the treatment of mood disorders

“…Moreover, for this specific localization around blood vessels, astrocytes might also be of clinical importance for the transport of therapeutic drugs from the bloodstream into the brain parenchyma. In a previous review [2], we already introduced a first example of a transport glycoprotein localized on end-feet of astrocytes, P-glycoprotein (P-gp), which is predictive of a positive clinical response to ADs that are substrate of this protein [18]. Furthermore, it has been shown that another end-feet protein, Aquaporin-4 (Aqp-4), which is additionally expressed in adult stem cells, could regulate responses to fluoxetine on behavioral measures of depressive-like phenotypes in a chronic stress model of depression [19].…”

“…Moreover, investigating cell type-specific differences that might be responsible for the pathogenesis of brain disorders may open the avenue for a deeper examination of cellular responses to pharmacological treatments, thereby helping to optimize current treatment strategies or identify alternative targets for drug discovery. In a previous work, we already provided a detailed description of the main subtypes of glia cells, their functions and how we think that they might be involved in the pathogenesis of several neuropsychiatric disorders and in response to pharmacologic treatments [2]. Therefore, here we provide a more focused description on the functional role of astrocytes at the synaptic and vascular compartments.…”