Animal model of autism induced by prenatal exposure to valproate:altered glutamate metabolism in the hippocampus

Bristot Silvestrin, Roberta and Bambini-Junior, Victorio and Galland, Fabiana and Daniele Bobermim, Larissa and Quincozes-Santos, André and Torres Abib, Renata and Zanotto, Caroline and Batassini, Cristiane and Brolese, Giovana and Gonçalves, Carlos-Alberto and Riesgo, Rudimar and Gottfried, Carmem (2013) Animal model of autism induced by prenatal exposure to valproate:altered glutamate metabolism in the hippocampus. Brain Research, 1495. pp. 52-60. ISSN 0006-8993

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Autism spectrum disorders (ASD) are characterized by deficits in social interaction, language and communication impairments and repetitive and stereotyped behaviors, with involvement of several areas of the central nervous system (CNS), including hippocampus. Although neurons have been the target of most studies reported in the literature, recently, considerable attention has been centered upon the functionality and plasticity of glial cells, particularly astrocytes. These cells participate in normal brain development and also in neuropathological processes. The present work investigated hippocampi from 15 (P15) and 120 (P120) days old male rats prenatally exposed to valproic acid (VPA) as an animal model of autism. Herein, we analyzed astrocytic parameters such as glutamate transporters and glutamate uptake, glutamine synthetase (GS) activity and glutathione (GSH) content. In the VPA group glutamate uptake was unchanged at P15 and increased 160% at P120; the protein expression of GLAST did not change neither in P15 nor in P120, while GLT1 decreased 40% at P15 and increased 92% at P120; GS activity increased 43% at P15 and decreased 28% at P120; GSH content was unaltered at P15 and had a 27% increase at P120. These data highlight that the astrocytic clearance and destination of glutamate in the synaptic cleft might be altered in autism, pointing out important aspects to be considered from both pathophysiologic and pharmacological approaches in ASD.

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Journal Article
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Brain Research
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Copyright © 2012 Elsevier B.V. All rights reserved.
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12 Apr 2022 14:40
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19 Sep 2023 02:47