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Volume 12
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Article

The State of the Dopaminergic and Glutamatergic Systems in the Valproic Acid Mouse Model of Autism Spectrum Disorder

by
Alexandre Maisterrena
1,†,
Emmanuel Matas
1,†,
Helene Mirfendereski
2,3,
Anais Balbous
1,3,
Sandrine Marchand
2,3 and
Mohamed Jaber
1,3,*
1
Laboratoire de Neurosciences Expérimentales et Cliniques, Inserm, Université de Poitiers, 86000 Poitiers, France
2
Pharmacologie des Agents Anti-Infectieux et Antibiorésistance, Inserm, Université de Poitiers, 86000 Poitiers, France
3
CHU de Poitiers, 86000 Poitiers, France
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomolecules 2022, 12(11), 1691; https://doi.org/10.3390/biom12111691
Submission received: 17 October 2022 / Revised: 9 November 2022 / Accepted: 11 November 2022 / Published: 15 November 2022
(This article belongs to the Special Issue Biogenic Amines, Their Receptors and Transporters in Health and Disease: Commemorative Issue in Honor of Professor Marc G. Caron (1946–2022))
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Abstract

Autism Spectrum Disorder (ASD) is a progressive neurodevelopmental disorder mainly characterized by deficits in social communication and stereotyped behaviors and interests. Here, we aimed to investigate the state of several key players in the dopamine and glutamate neurotransmission systems in the valproic acid (VPA) animal model that was administered to E12.5 pregnant females as a single dose (450 mg/kg). We report no alterations in the number of mesencephalic dopamine neurons or in protein levels of tyrosine hydroxylase in either the striatum or the nucleus accumbens. In females prenatally exposed to VPA, levels of dopamine were slightly decreased while the ratio of DOPAC/dopamine was increased in the dorsal striatum, suggesting increased turn-over of dopamine tone. In turn, levels of D1 and D2 dopamine receptor mRNAs were increased in the nucleus accumbens of VPA mice suggesting upregulation of the corresponding receptors. We also report decreased protein levels of striatal parvalbumin and increased levels of p-mTOR in the cerebellum and the motor cortex of VPA mice. mRNA levels of mGluR1, mGluR4, and mGluR5 and the glutamate receptor subunits NR1, NR2A, and NR2B were not altered by VPA, nor were protein levels of NR1, NR2A, and NR2B and those of BDNF and TrkB. These findings are of interest as clinical trials aiming at the dopamine and glutamate systems are being considered.
Keywords: dopamine; glutamate; autism spectrum disorder; valproic acid; mouse models; striatum; cerebellum; accumbens dopamine; glutamate; autism spectrum disorder; valproic acid; mouse models; striatum; cerebellum; accumbens

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MDPI and ACS Style

Maisterrena, A.; Matas, E.; Mirfendereski, H.; Balbous, A.; Marchand, S.; Jaber, M. The State of the Dopaminergic and Glutamatergic Systems in the Valproic Acid Mouse Model of Autism Spectrum Disorder. Biomolecules 2022, 12, 1691. https://doi.org/10.3390/biom12111691

AMA Style

Maisterrena A, Matas E, Mirfendereski H, Balbous A, Marchand S, Jaber M. The State of the Dopaminergic and Glutamatergic Systems in the Valproic Acid Mouse Model of Autism Spectrum Disorder. Biomolecules. 2022; 12(11):1691. https://doi.org/10.3390/biom12111691

Chicago/Turabian Style

Maisterrena, Alexandre, Emmanuel Matas, Helene Mirfendereski, Anais Balbous, Sandrine Marchand, and Mohamed Jaber. 2022. "The State of the Dopaminergic and Glutamatergic Systems in the Valproic Acid Mouse Model of Autism Spectrum Disorder" Biomolecules 12, no. 11: 1691. https://doi.org/10.3390/biom12111691

APA Style

Maisterrena, A., Matas, E., Mirfendereski, H., Balbous, A., Marchand, S., & Jaber, M. (2022). The State of the Dopaminergic and Glutamatergic Systems in the Valproic Acid Mouse Model of Autism Spectrum Disorder. Biomolecules, 12(11), 1691. https://doi.org/10.3390/biom12111691

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