Unusually high levels of the signaling peptide BDNF, or brain-derived neurotrophic factor, have been detected in blood samples from children with autism. Barbara Hempstead of Weill Medical College at Cornell University and her colleagues propose that BDNF may also be over-expressed in the brains of these children, causing neurological defects that lead to the disorder.

During brain development, BDNF regulates the birth and differentiation of brain cells, or neurons. Some of BDNF’s target cells, such as cortical interneurons, which transmit information between different layers of the brain cortex, have been implicated in autism. BDNF is also a regulator of brain growth, and children with the disorder tend to have abnormally large brains during early development. What’s more, MeCP2, a gene in which mutations are known to cause the autism-related Rett syndrome, directly regulates the expression of BDNF.

Hempstead and colleagues have preliminary evidence that both neurons and blood platelets regulate BDNF expression using similar mechanisms, suggesting that people who produce high levels in one tissue are also likely to have high levels in the other. Whether increased BDNF signaling disrupts human neural development and causes autism, however, is unknown.

To test their hypothesis, the researchers first plan to determine the neurological consequences of expressing too much BDNF in specific regions of the mouse brain known to develop abnormally in autism. Altered mice that modestly overexpress BDNF were analyzed for social interaction–related behaviors and found to have increased interaction time with novel mice placed in the interaction chamber, compared with wild-type littermate controls. There was no difference in baseline anxiety-related behaviors. These findings highlight an unexpected role of BDNF in increasing social interaction, when overexpressed at low to intermediate levels (10-30% above controls).

The researchers also aim to test whether BDNF levels in the blood are altered in children with autism. Hempstead and colleagues are analyzing BDNF processing, BDNF levels and BDNF receptors in human platelets and serum from patients and immediate family members. If high BDNF levels do prove to be a cause of the disorder, drugs that block its production or signaling might be an effective treatment for autism.