MIDB Researchers Receive Award to Reveal a Common Impairment Underlying Diverse Neurodevelopmental Disorders

Thomas Bastian, PhD, assistant professor in the Department of Pediatrics, and Zhe Chen, PhD, assistant professor in the Department of Neuroscience, recently received a Masonic Cross-Departmental Grant in Children’s Health Research to study specific genes and their effects on mitochondrial function.

Establishing the neural networks that underlie sensorimotor, cognitive, and social functions involves key developmental processes, including neurogenesis, axon growth, branching, and guidance, and synapse formation and maturation. The mitochondrion is a specialized cell compartment that performs many functions that are critical for brain development, including generating energy, synthesizing lipids, buffering calcium ion, and regulating cell death.

“Mitochondrial dysfunction has been increasingly implicated in neurodevelopmental abnormalities that are identified in various neurological and psychiatric disorders, including autism, ADHD, and depression. However, due to the diverse clinical manifestations, we have limited knowledge in identifying neurodevelopmental abnormalities that have an underlying association with mitochondrial impairment,” said Bastian. “Our recent research has provided a novel perspective in understanding a similar group of neurological disorders, including split-brain syndrome, schizophrenia, OCD, bipolar disorder, ADHD, depression, and autism, that involve the dysregulation of a pair of genes named Netrin1 and DCC. Therefore, despite the widely heterogenous clinical manifestations, these DCC-associated disorders, which overlap with those linked with mitochondria impairment, are likely to share common etiological factors.”

In this study, researchers will test the hypothesis that Netrin1/DCC deficiency impairs mitochondrial activities and consequently disrupts the development and maturation of the nervous system leading to long-term risk of neurobehavioral deficits. They also hope to discover pharmacological agents that have the potential to alleviate the associated mitochondrial dysfunction.

“Together, the successful completion of our study will reveal a common impairment underlying diverse neurodevelopmental disorders and will identify the molecules that can be targeted for treatments,” said Chen.

Funded through the University of Minnesota Department of Pediatrics, the Masonic Cross-Departmental Grants in Children’s Health Research support interdisciplinary research in children’s health that is innovative and has a high potential for future funding and discovery.