The finding focuses on a faulty molecular mechanism that may underlie ASD’s cognitive impairments. The discovery could lead to future treatments targeting a brain enzyme that controls the formation of a neuronal structure called dendrites, according to lead author Li-Huei Tsai, Picower Professor of Neuroscience and director of the Picower Institute.
Dendrites are neurons’ spiky, branchlike projections. Dendrites at the apex of the cell body are known as apical; dendrites that emerge from the bottom are called basal. Basal dendrites, studded with synapses, receive electrical signals sent by other neurons within the brain.
Researchers have pointed to aberrant dendrite formation as the culprit behind developmental and psychiatric disorders such as autism and schizophrenia.
Basal dendrites that are too sparse or badly formed “change the connectivity within the brain,” said study co-author Froylan Calderon de Anda, a postdoc at the Picower Institute. “The flow of information among brain regions is affected.”
Forging a pathway
Deleted or duplicated genes on chromosome 16 have been tied to ASD. Some of the genes on chromosome 16 are known to help shape brain cells, but the molecular pathways controlling the formation of basal dendrites is not well-understood.
Tsai, who is also a Howard Hughes Medical Institute investigator, Calderon de Anda and colleagues from Johns Hopkins University School of Medicine looked at a gene encoding an enzyme that helps shape dendrites in the cortex, hippocampus and amygdala — brain regions associated with complex cognitive functions.
The researchers found that underexpressing the gene led to too few dendrite branches; overexpressing it created too many.
Calderon de Anda, who studies how neurons grow and take shape, said it was surprising to see a specific molecular pathway dedicated to basal dendrites.
“Everybody thought dendrites were just dendrites, and the molecular pathways were the same [for the two types of dendrites],” he said. “But they don’t share pathways. Now it’s clear it’s more complex. Basal dendrites share more in common with the formation of axons [the long thin projections that transmit electrochemical signals to other neurons] than with apical dendrites.”
Next steps include developing animal models to manipulate the enzyme produced by the targeted ASD gene, hopefully shedding light on how malformed dendrites affect cognition.
This work was supported by the Simons Foundation Autism Research Initiative.