Research shows that polychlorinated biphenyl, or PCB exposure launches a cellular chain of events that leads to an overabundance of dendrites, the filament-like projections that conduct electrochemical signals between neurons, and disrupts normal patterns of neuronal connections in the brain.
“Dendrite growth and branching during early development is a finely orchestrated process, and the presence of certain PCBs confuses the conductor of that process,” said researcher Pamela Lein. “Impaired neuronal connectivity is a common feature of a number of conditions, including autism spectrum disorders.”
The findings underscore the developing brain’s vulnerability to environmental exposures and demonstrate how PCB exposure could add to autism risk.
“We don’t think PCB exposure causes autism,” Lein said, “but it may increase the likelihood of autism in children whose genetic makeup already compromises the processes by which neurons form connections.”
The researchers found that key cellular players, called calcium and calmodulin kinases, are activated by increased calcium levels. Activated calmodulin kinase then turns on the protein known as CREB that regulates genes that produce Wnt2, a potent molecule and the final arbiter of whether and how dendrites grow. Wnt2 directs structural proteins to construct scaffolding that supports dendrite growth and branching.
“Orderly choreography of the calmodulin kinase-to-Wnt2 pathway translates normal increases in calcium levels into normal levels of dendrite production,” said lead author Gary Wayman. “The wiring of billions of neurons is dependent on the health of this cellular process and is crucial to proper development of virtually all complex behaviors, learning, memories and language.”
For the current studies, the team set out to determine if that pathway was altered by to PCB exposure, focusing on neurons of the hippocampus, the brain region linked with learning and memory and known to suffer impaired connectivity in many neurodevelopmental disorders.
One of the current studies examined dendrite growth in rat pups born to and nursed by mothers subjected to PCB exposure. Another study analyzed how PCBs affect rat neurons in cell cultures at developmental stages similar to those in the third trimester of pregnancy in humans. In both studies, PCB exposure levels were similar to those found in the human diet and in human tissues, including the placenta and breast milk.
Evaluation of the brains of the rats that had PCB exposure early in life showed significant overproduction of dendrites. The cellular studies showed that PCBs triggered the calcium pathway that led to the aberrant brain architecture, and that dendrite production was normal when that cellular pathway was blocked.
These same calcium pathways are implicated in some forms of autism and, while environmental exposures alone do not cause autism, these new findings provide good evidence that PCB exposure could add to autism risk in genetically predisposed children.
Reference for: PCB Exposure Could Increase Risk of Autism