January 9 – A groundbreaking study led by Indian-origin neuroscientist Dr. Viji Santhakumar has identified a gene, neuropilin2, as a key contributor to behavioral changes associated with autism spectrum disorder (ASD) and epilepsy. Published in Nature Molecular Psychiatry, the research paves the way for targeted therapies addressing these frequently co-occurring conditions.
Neuropilin2 encodes a receptor essential for cell-cell interactions in the brain, playing a pivotal role in neural circuit development. While previous studies have linked mutations in this gene to neurological disorders, the underlying mechanisms remained unclear until now.
Dr. Santhakumar and her team at the University of California–Riverside developed a mouse model to study the effects of deleting the neuropilin2 gene. Their experiments revealed that the absence of this gene disrupts the migration of inhibitory neurons, leading to an imbalance between excitatory and inhibitory signals in the brain.
“This imbalance leads to autism-like behaviors and an increased risk of seizures,” explained Dr. Santhakumar, a professor of molecular, cell, and systems biology.
Key Findings
- Impact on Neural Circuits: The study found that neuropilin2 deletion during a critical developmental phase impaired inhibitory circuit formation, resulting in behavioral rigidity, social interaction deficits, and heightened seizure susceptibility.
- Gene Influence: “Our results highlight the influence of a single gene on both excitatory and inhibitory systems in the brain,” said Dr. Santhakumar. “Disrupting inhibitory circuit development is sufficient to cause autism-related behaviors and epilepsy to co-occur.”
- Therapeutic Potential: The findings suggest that targeting specific phases of neuronal development could help prevent or alleviate symptoms of autism and epilepsy if detected early.
“By isolating the role of inhibitory circuit formation, we may develop therapeutic strategies to improve outcomes for individuals with autism, particularly those who experience seizures,” Dr. Santhakumar added.
Collaborators and Contributions
The research team included Deepak Subramanian, Andrew Huang, and Samiksha Komatireddy from UC-Riverside, alongside Carol Eisenberg, Jiyeon Baek, Haniya Naveed, Michael W. Shiflett, and Tracy S. Tran from Rutgers University.
The study represents a significant step in understanding the genetic and neurological links between autism and epilepsy, offering hope for more effective and early interventions.
