Navigation Links
Research shows how PCBs promote dendrite growth, may increase autism risk

(SACRAMENTO, Calif.) New research from UC Davis and Washington State University shows that PCBs, or polychlorinated biphenyls, launch 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 Pamela Lein, a developmental neurobiologist and professor of molecular biosciences in the UC Davis School of Veterinary Medicine. "Impaired neuronal connectivity is a common feature of a number of conditions, including autism spectrum disorders."

Reported today in two related studies in the journal Environmental Health Perspectives, the findings underscore the developing brain's vulnerability to environmental exposures and demonstrate how PCBs 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 senior authors of the studies were Lein and Isaac Pessah, chair of molecular biosciences in the School of Veterinary Medicine and director of the Center for Children's Environmental Health at UC Davis. Both are researchers with the UC Davis MIND Institute, which is dedicated to finding answers to autism and other neurodevelopmental disorders. The lead author was Gary Wayman of Washington State University's Program in Neuroscience, who first described the molecular pathway that controls the calcium signaling in the brain that guides normal dendrite growth.

Wayman 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 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 exposure to PCBs, focusing on neurons of the hippocampus the brain region linked with learning and memory and known to suffer impaired connectivity in many neurodevelopmental disorders.

The scientists also focused on the effects of an understudied PCB subset known as non-dioxin-like PCBs, which have been shown to increase calcium levels in neurons. Both non-dioxin-like PCBs and the more familiar dioxin-like subset were widely used in electrical equipment in the 1950s and 1960s. Banned in the 1970s because of the potential for dioxin-like PCBs to cause cancer, all PCBs are stable compounds that persist throughout the environment today.

One of the current UC Davis studies examined dendrite growth in rat pups born to and nursed by PCB-exposed mothers. 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 exposed to PCBs 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.

"We are the first to show that non-dioxin-like PCBs alter how the developing brain gets wired by hijacking the calcium signaling pathway and greatly expanding dendrite growth," said Lein.

The experiments also helped identify for the first time the specific trigger for this cellular chain of events as the ryanodine receptor (RyR) calcium channel. Pessah, a recognized leader in calcium-channel dysfunction and neurodevelopment, previously showed that RyR is selectively activated by non-dioxin-like PCBs. The new studies prove that RyR is a necessary component in the pathway that controls dendritic growth.

"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 PCBs could add to autism risk in genetically predisposed children," said Pessah. "Understanding the fundamental mechanisms by which PCBs alter neural networks sets the stage for research on environmental contaminants that are structurally related to PCBs, including flame retardants, and their risks to susceptible populations."

Contact: Karen Finney
University of California - Davis Health System

Related biology news :

1. Researchers announce GenomeSpace environment to connect genomic tools
2. BGI and Aspera collaborate on high-speed data exchange to advance genome research
3. Evidence shows that anti-depressants likely do more harm than good, researchers find
4. Scientists advance field of research with publication of newly validated method for analyzing flavanols in cocoa
5. Scripps research scientists find anticonvulsant drug helps marijuana smokers kick the habit
6. Johns Hopkins researchers uncover genes at fault for cystic fibrosis-related intestinal obstruction
7. Researchers find mechanism that gives plants balance
8. Research is ensuring stormwater systems are designed for the future
9. New research underscores the health benefits of fibers, including bone health
10. Research on carbon-consuming life-forms in Antarctica published in JoVE
11. Climate change may create price volatility in the corn market, say Stanford and Purdue researchers
Post Your Comments:
(Date:11/10/2015)... Nov. 10, 2015  In this report, ... basis of product, type, application, disease indication, ... this report are consumables, services, software. The ... safety biomarkers, efficacy biomarkers, and validation biomarkers. ... are diagnostics development, drug discovery and development, ...
(Date:11/9/2015)... , Nov. 9, 2015  Synaptics Inc. (NASDAQ: ... solutions, today announced broader entry into the automotive market ... that match the pace of consumer electronics human interface ... sensors are ideal for the automotive industry and will ... Europe , Japan ...
(Date:10/29/2015)...   MedNet Solutions , an innovative SaaS-based eClinical ... research, is pleased to announce that it has been ... one of only three finalists for a 2015 ... Growing" category. The Tekne Awards honor Minnesota ... innovation and leadership. iMedNet™ eClinical ...
Breaking Biology News(10 mins):
(Date:11/26/2015)... MUMBAI , November 26, 2015 ... --> Accutest Research ... accredited Contract Research Organization (CRO), has ... Chase Cancer Center - Temple Health ... ,     (Photo: ) ...
(Date:11/25/2015)... Studies reveal the differences in species of bacteria ... for more effective treatment for one of the most commonly ... --> --> Gum disease is one ... relatively little was understood about the bacteria associated with it ... researchers from the WALTHAM Centre for Pet Nutrition together with ...
(Date:11/25/2015)... 2015 Orexigen® Therapeutics, Inc. (Nasdaq: OREX ... fireside chat discussion at the Piper Jaffray 27th Annual ... The discussion is scheduled for Wednesday, December 2, at ... A replay will be available for 14 days after ... Julie NormartVP, Corporate Communications and Business Development , BrewLife(858) ...
(Date:11/24/2015)... , Nov. 24, 2015 Cepheid (NASDAQ: ... speaking at the following conference, and invited investors to ... NY      Tuesday, December 1, 2015 at 11.00 ... NY      Tuesday, December 1, 2015 at 11.00 ... Conference, New York, NY      Tuesday, ...
Breaking Biology Technology: