Vanderbilt University pharmacologists report evidence that aberrant spontaneous release of neurotransmitters in the brain can cause a range of severe intellectual and neurodevelopmental disorders in infants and children, according to a press release from the university.
The university said this is the first known research finding that suggests spontaneous neurotransmission causes disease. Previously, researchers thought only neurotransmission that had been evoked by electrical activity caused disease.
Neurons, the billions of cells constantly sharing information within the brain, communicate with each other but do not touch. They release chemicals called neurotransmitters, orchestrated by the SNARE protein complex, triggered by a wave of electrical activity.
Mutations of one of the proteins in the SNARE complex, SNAP25, are known to cause a variety of neurodevelopmental disorders. These can present with recurrent seizures, intellectual disability and autistic features in infants and children.
By examining the electrical signals of 10 different SNAP25 mutations among 11 patients, the researchers found that mutations of SNAP25 encourage anomalous neurotransmitter release both in response to electrical activity and independent of electrical signaling in the brain. More importantly, they identified the single mutation that causes spontaneous release – neurotransmitter release even in the absence of appropriate electrical activity.
Traditionally, the diagnosis of cognitive disorders caused by SNAP25 mutations has been so clinically challenging that researchers assume that their incidence is underestimated. In addition, the complete lack of understanding of the disease mechanism has made it impossible to develop therapeutics tailored to patients.
