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Cannabinoids and glial cells: possible mechanism to understand schizophrenia

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European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Clinical and neurobiological findings have reported the involvement of endocannabinoid signaling in the pathophysiology of schizophrenia. This system modulates dopaminergic and glutamatergic neurotransmission that is associated with positive, negative, and cognitive symptoms of schizophrenia. Despite neurotransmitter impairments, increasing evidence points to a role of glial cells in schizophrenia pathobiology. Glial cells encompass three main groups: oligodendrocytes, microglia, and astrocytes. These cells promote several neurobiological functions, such as myelination of axons, metabolic and structural support, and immune response in the central nervous system. Impairments in glial cells lead to disruptions in communication and in the homeostasis of neurons that play role in pathobiology of disorders such as schizophrenia. Therefore, data suggest that glial cells may be a potential pharmacological tool to treat schizophrenia and other brain disorders. In this regard, glial cells express cannabinoid receptors and synthesize endocannabinoids, and cannabinoid drugs affect some functions of these cells that can be implicated in schizophrenia pathobiology. Thus, the aim of this review is to provide data about the glial changes observed in schizophrenia, and how cannabinoids could modulate these alterations.

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Abbreviations

∆9-THC:

Delta-9-tetrahydrocannabinol

2-AG:

2-Arachidonoylglycerol

AEA:

Anandamide

CB1:

Type 1 cannabinoid receptor

CB2:

Type 2 cannabinoid receptor

CNR1:

Cannabinoid receptor type-1 gene

CNR2:

Cannabinoid receptor type-2 gene

COX:

Cyclooxygenase

DAGLα:

Diacylglycerol lipase alpha

DAGLβ:

Diacylglycerol lipase beta

DISC-1:

Disrupted in schizophrenia-1

FAAH:

Fatty acid amide hydrolase

GFAP:

Glial fibrillary acid protein

GLAST:

Glutamate aspartate transporter

GLT-1:

Astrocytic glutamate transporter-1

GPR55:

G protein-coupled receptor 55

IL-1:

Interleukin 1

IL-6:

Interleukin 6

KO:

Knockout

LPS:

Lipopolysaccharide

MAGL:

Monoacylglycerol lipase

NAPE:

N-Acyl-phosphatidylethanolamine-phospholipase

NMDA:

N-Methyl-d-aspartate

OPCs:

Oligodendrocyte precursor cells

PPARγ:

Peroxisome proliferator-activated receptor

TNF-α:

Tumor necrosis factor alpha

TRPV1:

Transient receptor potential vanilloid 1

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Acknowledgements

This work was supported by Grant from the ‘Fundação de Amparo à Pesquisa do Estado de São Paulo’ (FAPESP Grant number 2013/08711-3 and 2014/10068-4), ‘Coordenação de Aperfeiçoamento de Pessoal de Nível Superior’ (Capes Grant number 1656470), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq Grant 460289/2014-4). DMS is also supported by Instituto Serrapilheira, Brazil (grant G-1709-16349).

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Authors and Affiliations

  1. Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Rua Monteiro Lobato 255, Campinas, SP, 13083-862, Brazil

    Valéria de Almeida & Daniel Martins-de-Souza

  2. Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBION), Conselho Nacional de Desenvolvimento Científico e Tecnológico, São Paulo, Brazil

    Daniel Martins-de-Souza

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  1. Valéria de Almeida
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AV conceived the study, designed, and wrote the first draft and final version of manuscript. MSD conceived, supervised, and finalized the manuscript.

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Correspondence to Valéria de Almeida.

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de Almeida, V., Martins-de-Souza, D. Cannabinoids and glial cells: possible mechanism to understand schizophrenia. Eur Arch Psychiatry Clin Neurosci 268, 727–737 (2018). https://doi.org/10.1007/s00406-018-0874-6

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