Final published version
Licence: Other
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
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 -