Update on the Neurobiology of Schizophrenia: a Role for Extracellular Microdomains

Overview

Journal Minerva Psichiatr

Specialty Psychiatry

Date 2013 Oct 1

PMID 24077131

Citations 15

Authors

D Shan

S Yates

R C Roberts

R E McCullumsmith

Affiliations

Soon will be listed here.

Abstract

The glutamate system includes presynaptic glutamatergic terminals, complex post-synaptic densities found on diverse types of neurons expressing glutamate receptors, as well as glutamate transporters and enzymes that facilitate the glutamate/glutamine cycle. Abnormalities of this system have been implicated in schizophrenia based on an accumulating body of evidence from postmortem, imaging, and preclinical studies. However, recent work has suggested that astrocytes may have more than a bystander role in the synchronization of neuronal responses in the brain. Converging evidence suggests that extrasynaptic glutamate microdomains are formed by astrocytes and may facilitate neuroplasticity via the modulation of extra-synaptic glutamate receptors on neuronal membranes within these domains. In this article the authors propose that the composition and localization of protein complexes in glutamate microdomains is abnormal in schizophrenia, leading to pathological neuroplastic changes in the structure and function of glutamate circuits in this illness.

Citing Articles

Molecular signature of extracellular matrix pathology in schizophrenia.

Pantazopoulos H, Katsel P, Haroutunian V, Chelini G, Klengel T, Berretta S Eur J Neurosci. 2020; 53(12):3960-3987.

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Increased inflammation and brain glutamate define a subtype of depression with decreased regional homogeneity, impaired network integrity, and anhedonia.

Haroon E, Chen X, Li Z, Patel T, Woolwine B, Hu X Transl Psychiatry. 2018; 8(1):189.

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Involvement of extrasynaptic glutamate in physiological and pathophysiological changes of neuronal excitability.

Pal B Cell Mol Life Sci. 2018; 75(16):2917-2949.

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Cell-subtype-specific changes in adenosine pathways in schizophrenia.

ODonovan S, Sullivan C, Koene R, Devine E, Hasselfeld K, Moody C Neuropsychopharmacology. 2018; 43(8):1667-1674.

PMID: 29483661 PMC: 6006250. DOI: 10.1038/s41386-018-0028-6.

The role of glutamate transporters in the pathophysiology of neuropsychiatric disorders.

ODonovan S, Sullivan C, McCullumsmith R NPJ Schizophr. 2017; 3(1):32.

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