Advanced Glycation End Products And Autism- Evidence For A Connection | 12453
Journal of Alzheimers Disease & Parkinsonism
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Autism is a complex and heterogeneous neurodevelopmental disorder of unknown etiology which results from both genetic
and environmental factors. Among the environmental factors associated with autism are maternal obesity and diabetes.
AGEs are a heterogeneous group of macromolecules that are formed by the non-enzymatic glycation of proteins, lipids and nucleic
acids. AGEs are implicated in diabetic complications and can induce oxidative stress and inflammation. Humans are exposed to
two sources of AGEs: exogenous AGEs that are ingested in foods and endogenous AGEs that are formed in the body. Diets with a
high glycemic index are also associated with the accumulation of AGEs in the body. To test the hypothesis that AGEs contribute
to the development of autism we used BTBR mice, a genetically homogeneous inbred strain of mice that displays behavioral
traits that reflect all three diagnostic symptoms of autism including abnormal social interactions, impaired communication
and repetitive behavior. Adult female mice were fed either a low or high glycemic diet beginning prior to impregnation. Their
offspring were fed the same diet and at 10 weeks of age male mice were tested for behavioral markers of autism. We show
that the BTBR mice continuously exposed to a low glycemic diet beginning at conception showed significant reductions in
multiple, autism-associated behaviors including repetitive grooming and perseveration. Overall, these data suggest that AGEs,
a major consequence of diabetes, can contribute to the development of an autistic phenotype and suggest that maternal dietary
modifications could have an impact on the development of autism.
Pamela Maher obtained her Ph.D. in Biochemistry from the University of British Columbia followed by postdoctoral studies at the University of
California, San Diego. Over the last 10 years her research has evolved from basic studies on the mechanisms underlying nerve cell survival and
death to more translationally-oriented research on the development of approaches to prevent neurological disorders. She has over 100 publications
in peer-reviewed journals. Her research is currently funded by NIH.
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