Title:Valproic Acid and Propionic Acid Modulated Mechanical Pathways Associated
with Autism Spectrum Disorder at Prenatal and Neonatal Exposure
Volume: 21
Issue: 5
Author(s): Amit Raj Sharma, Gitika Batra , Lokesh Saini, Saurabh Sharma, Abhishek Mishra, Rubal Singla, Ashutosh Singh , Rahul Soloman Singh, Ashish Jain , Seema Bansal, Manish Modi and Bikash Medhi*
Affiliation:
- Department of Pharmacology, Post Graduate Institute for Medical Education and Research (PGIMER), Chandigarh, India
Keywords:
Autism spectrum disorder, valproic acid, propionic acid, neuro-inflammation, neonatal development, gut microbiota.
Abstract: Autism spectrum disorder (ASD) is a composite disorder of brain development with uncertain
etiology and pathophysiology. Genetic factors are important in ASD causation, although environmental
factors are also involved in ASD pathophysiology. Environmental factors might affect
the genetic processes of brain development through the modulation of molecular pathways that
might be involved with ASD. Valproic acid and propionic acid are the major environmental factors
that serve as medicine and food preservative. VPA is used as an anti-epileptic medicine, but it has
adverse effects on pregnant women and alters the developmental patterns of the embryo. It is a multi-
targeting agent and affects 5-HT, GABA, etc. PPA is a secondary metabolite of gut microbiota
that is commonly used as a food preservative. PPA plays a significant role in ASD causation by altering
the several developmental molecular pathways like PTEN/Akt, mTOR/Gskβ, Cytokines activated
pathways, etc., at the prenatal and neonatal stage. Moreover, ASD complexity might be increased
by other important factors like vitamin A deficiency. Vitamin A is important for cortical
brain development and neuronal cell differentiation. Additionally, several important genes such as
RELN, Lhx2, CREB, IL-6, NMDA, BDNF, etc., are also altered in ASD and involved in brain development,
central nervous system, and enteric nervous system. These genes affect neuronal differentiation,
hyperactivity, oxidative stress, oxytocin, and GABA imbalance lead to improper behavior
in autistic individuals. These genes are also studied in VPA and PPA ASD-like animal models.
In this review, we explored the mechanical pathways that might be altered with VPA and PPA
exposures at the embryonic developmental stage or neonatal developmental stage.
