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Reduced Brain-Derived Neurotrophic Factor in the Cerebellum of Autistic Postmortem Brain Tissue: Implications for Serotonergic Pathways in the Pathogenesis of Autism

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Session 7: Autism Brain Tissue Panel-Progress and Future Strategies

Robert Lopez-Alberola

Little work has been done looking at neuronal growth factor expression in autism. Brain-derived neurotrophic factor (BDNF), in particular, is of interest because of its putative interaction with serotonergic pathways, which have been implicated in autism. BDNF has been shown to promote serotonin production and is important in neuronal survival, eliciting sprouting form serotonergic neutons and increasing serotonin turnover. We utilized immunohistochemical staining techniques coupled with computerized digital quantitation in analyzing paraffin-embedded human autopsy tissue to assay BDNF expression in the cerebellum of 8 autistic males (age: 8-56 yrs) and 9 controls, age/gender matched. Cerebellar tissue was chosen because of consistent neuropathological/imaging abnormalities in autistic patients.

The results showed a significant reduction of BDNF in autistic patients in both Purkinje cells and the molecular layer neuropil (p=0.008 and p=0.004, respectively). This is consistent with the involvement of the serotonergic brain pathways, especially the dentatothalamocortical, in the pathogenesis of autism. This also raises the possibility of an animal model for autism, since BDNF 'knock-out' mice (-/-) show a three-fold increase in cerebellar granule cell death and the Purkinje cells have extremely stunted dendritic trees, both of which are pathological features of autism.

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Last Reviewed: 11/30/2012
Vision National Institutes of Health Home BOND National Institues of Health Home Home Storz Lab: Section on Environmental Gene Regulation Home Machner Lab: Unit on Microbial Pathogenesis Home Division of Intramural Population Health Research Home Bonifacino Lab: Section on Intracellular Protein Trafficking Home Lilly Lab: Section on Gamete Development Home Lippincott-Schwartz Lab: Section on Organelle Biology