4.7 Article

Sonic hedgehog pathway as a new target of atypical antipsychotics: Revisiting of amisulpride and aripiprazole effects in a rat model of schizophrenia

Journal

LIFE SCIENCES
Volume 316, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2022.121366

Keywords

Schizophrenia; Sonic hedgehog; Amisulpride; Aripiprazole; Cognition; BDNF

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This study tested the effects of antipsychotic drugs amisulpride and/or aripiprazole on the Sonic hedgehog (Shh)-pathway, cognitive functions, and neurogenesis in a rat model of schizophrenia. The results showed that social isolation led to cognitive dysfunction, disorganized Shh-pathway proteins, and increased glial fibrillary acidic protein (GFAP)-stained astrocytes. However, treatment with these drugs reversed these changes, increasing Shh, transmembrane patched-1 and smoothened, glioma-associated-oncogene (GLI)-1 levels, dopamine-1 receptors and brain derived neurotrophic factor, and decreasing GLI-3 protein, GFAP immune reaction in astrocytes, and inflammatory markers.
Objectives: Schizophrenia is a chronic mental illness presented by cognitive deficits that precede its positive and negative symptoms. Sonic hedgehog (Shh)-pathway contributes to its pathophysiology. Shh has a role in neu-rogenesis as it regulates proliferation and survival of neural cells. In this study, effects of the anti-psychotics Amisulpride and/or Aripiprazole on the Shh-pathway and its relation to cognitive functions and neurogenesis in a rat model of schizophrenia were tested.Methods: 60 male Wistar rats were allocated into the following groups: control, socially isolated, amisulpride and/or aripiprazole-treated groups. Rats were then subjected to behavioral, biochemical, and histopathological tests to assess the impact of these drugs on Shh-pathway.Key findings: Cognitive-dysfunction was evidenced in socially isolated group in novel object, three-chamber, and Morris water maze tests, associated by disorganised Shh-pathway proteins levels concentrations, increased glial fibrillary acidic protein (GFAP)-stained astrocytes. Treated groups favorably reversed these changes evidenced by increased Shh, transmembrane patched-1 and smoothened, glioma-associated-oncogene (GLI)-1 levels, dopamine-1 receptors and brain derived neurotrophic factor, and decreased GLI-3 protein, GFAP immune re-action in astrocytes and inflammatory markers compared to socially isolated group.Conclusion: Amisulpride and/or aripiprazole have a favorable role in turning on Shh-pathway with subsequent beneficial cognitive and neurogenesis effects.

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