Unraveling the complex mechanisms underlying autism spectrum disorder and epilepsy, a team of global researchers, led by Indian-origin neuroscientist Viji Santhakumar has detected a gene that contributes to the development of behavioural changes associated with the neurological conditions.
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, said the researchers in the study published in journal Nature Molecular Psychiatry.
Earlier research has linked mutations in neuropilin2 to neurological disorders like autism and epilepsy, but the mechanisms involved have remained largely unclear.
However, the study led by Santhakumar offers a pathway for future treatments aimed at alleviating some challenging symptoms of these frequently co-occurring conditions.
As per the study, 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 the 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.
The study was co-authored 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.
By focusing on the timing of gene expression during key developmental windows, researchers may be able to intervene early, which could alter the trajectory of these disorders, say neurologists.
The study underscores the importance of understanding the interplay between genetics and neural circuit development, and it opens the door to exploring how therapeutic strategies could improve the quality of life for individuals with autism and epilepsy, they added.
