Abstract
Valproic acid (VPA) induced rodent model of autism is a widely accepted and extensively used rodent model to investigate the pharmacotherapy against autism. But, to date, its validation, suitability, and applicability as a well defining autistic model are still questionable. Previous research efforts highlighted that this model shows various core defining features of autism and related pathways, hence it is very necessary to explore its authenticity as a well-suited model for autism. Therefore, in this review, we summarize the preclinical and neurobiological relevant validated features, involved etiological mechanism, biological markers, treatment responses, drawbacks, current approaches, and future perspectives of VPA-induced model of autism. This review would help in deciphering the validation of the VPA-induced autistic model and its suitability as an experimental model of autism. A thorough investigation of behavioral, molecular, and neurobiological processes in animal models of autism would help in investigating the exact causation and effective treatment for autism.
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Availability of Data and Materials
All cited data is available on online database websites like PubMed, Web of Science, Scopus. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
Abbreviations
- VPA:
-
Valproic acid
- ASD:
-
Autism spectrum disorder
- Ngn2:
-
Neurogenin 2
- Tbe2:
-
Tcf-4-binding element 2
- NeuroD1:
-
Neuronal differentiation 1
- NMDAR:
-
N-methyl-D-aspartate receptor
- AMPAR:
-
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
- PAX6:
-
Paired box protein 6
- SphK2:
-
Sphingosine kinase 2
- GABAARA4:
-
Gamma-aminobutyric acid type A receptor alpha 4
- GAD67:
-
Glutamic acid decarboxylase 67
- bcl-2:
-
B cell lymphoma 2
- Bax:
-
Bcl2-associated X protein
- akt:
-
Protein kinase B
- mTOR:
-
Mammalian target of rapamycin
- p-mTOR:
-
Phospho-mammalian target of rapamycin
- p-S6:
-
Phospho-S6 Ribosomal protein
- Atg:
-
Autophagy-related gene
- LC3-II:
-
Microtubule-associated protein 1A/1B-light chain 3
- Hes1:
-
Hairy and enhancer of split-1
- p-GSK-3β:
-
Phosphorylated-glycogen synthase kinase 3 beta
- ERK:
-
Extracellular signal-regulated kinase
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Ms. Sweety Mehra (first authorship): Concept preparation, literature search, review writing, and diagram preparation, Dr. Aitizaz Ul Ahsan (second authorship): Concept discussions, and editing. Ms. Era Seth (third authorship): Proofreading. Dr. Mani Chopra (corresponding author): Mechanical insights of the concept, technical guidance, editing, review, and proofreading.
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Mehra, S., Ul Ahsan, A., Seth, E. et al. Critical Evaluation of Valproic Acid-Induced Rodent Models of Autism: Current and Future Perspectives. J Mol Neurosci 72, 1259–1273 (2022). https://doi.org/10.1007/s12031-022-02033-7
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DOI: https://doi.org/10.1007/s12031-022-02033-7