TY - JOUR

T1 - Animal model of autism induced by prenatal exposure to valproate

T2 - altered glutamate metabolism in the hippocampus

AU - Bristot Silvestrin, Roberta

AU - Bambini-Junior, Victorio

AU - Galland, Fabiana

AU - Daniele Bobermim, Larissa

AU - Quincozes-Santos, André

AU - Torres Abib, Renata

AU - Zanotto, Caroline

AU - Batassini, Cristiane

AU - Brolese, Giovana

AU - Gonçalves, Carlos-Alberto

AU - Riesgo, Rudimar

AU - Gottfried, Carmem

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2013/2/7

Y1 - 2013/2/7

N2 - 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.

AB - 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.

KW - Animals

KW - Anticonvulsants/adverse effects

KW - Astrocytes/drug effects

KW - Autistic Disorder/chemically induced

KW - Disease Models, Animal

KW - Female

KW - Glutamic Acid/metabolism

KW - Hippocampus/metabolism

KW - Male

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects/chemically induced

KW - Rats

KW - Rats, Wistar

KW - Valproic Acid/adverse effects

U2 - 10.1016/j.brainres.2012.11.048

DO - 10.1016/j.brainres.2012.11.048

M3 - Journal article

C2 - 23219577

VL - 1495

SP - 52

EP - 60

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -