Indian-origin researcher finds gene behind autism and seizures

New York: A team of researchers, led by Indian-origin neuroscientist Viji Santhakumar, has found a gene that contributes to the development of behavioural changes associated with autism spectrum disorder and epilepsy.

The gene, called neuropilin2, encodes a receptor involved in cell-cell interactions in the brain and plays a key role in regulating the development of neural circuits.

The study, published in Nature Molecular Psychiatry, offers a pathway for future treatments aimed at alleviating some challenging symptoms of these frequently co-occurring conditions.

Earlier research has linked mutations in neuropilin2 to neurological disorders like autism and epilepsy, but the mechanisms involved have remained largely unclear.

Santhakumar and her collaborators from University of California–Riverside created a mouse model to examine the consequences of deleting the neuropilin2 gene.

They found the absence of neuropilin2 impairs the migration of inhibitory neurons, disrupting the delicate balance between excitatory and inhibitory signals in the brain.

“This imbalance leads to autism-like behaviours and an increased risk of seizures,” said Santhakumar, professor of molecular, cell and systems biology.

“The study results highlight how a single gene can influence both the excitatory and inhibitory systems in the brain. We show that disrupting inhibitory circuit development is sufficient to cause autism-related behaviours and epilepsy to co-occur,” Santhakumar added.

By selectively deleting neuropilin2 during a key developmental window, the researchers found impairments in inhibitory regulation of the circuit, which led to deficits in behavioural flexibility, social interactions, and an increased risk for seizures.

The study findings suggest that targeting specific phases of neuronal development could open new doors for therapeutic interventions, potentially preventing the onset of these disorders if detected early.

“By isolating the role of inhibitory circuit formation, we may be able to develop therapeutic strategies that could improve outcomes for individuals with autism, particularly those who experience seizures,” Santhakumar said.

Santhakumar was joined in the study by Deepak Subramanian, Andrew Huang, and Samiksha Komatireddy of UC-Riverside; and Carol Eisenberg, Jiyeon Baek, Haniya Naveed, Michael W. Shiflett, and Tracy S. Tran of Rutgers University.