Malav Trivedi, who recently completed his PhD in the laboratory of Prof. Richard Deth, has received a $95,000 postdoctoral research fellowship provided by the A2 Corporation, a New Zealand-based supplier of milk and dairy products. The fellowship will support further characterization of epigenetic and transcriptional changes in neuronal cells produced by food-derived opiate peptides, and their potential significance for neurodevelopmental and neurological disorders. Malav’s thesis research project focused on the ability of morphine and food-derived opiate peptides to affect synthesis of the antioxidant glutathione, with consequences for DNA methylation and gene expression. Digestion of milk and wheat/rye yields stable peptides, including β-casomorphin-7 (βCM7) and α-gliadin-7 (αG7), respectively, which activate opiate receptors at low nanomolar concentrations. These peptides are reported to be present in high abnormal amounts in blood and urine samples from autistic and schizophrenic patients. A Single Nucleotide Polymorphism (SNP) in β-casein results in higher amounts of βCM7 being produced from the milk of certain cows (A1 vs. A2), and several studies have shown a correlation between A1 milk consumption and inflammatory disorders. Malav characterized the effects of these food-derived opioid peptides on the pattern of DNA methylation in cultured neuronal cells, as well as subsequent gene expression changes using genome-wide microarray technology. His results indicate that opioids and food-derived opioid peptides induce oxidative stress and epigenetic changes which might affect development and neuroplasticity. These findings are also relevant to the reported health benefits of a gluten-free/casein-free (GF/CF) diet. Future work will focus on investigating the effects of these peptides on the methylation status of Long Interspersed Nuclear Elements (LINE-1 or L1) retrotransposons, as well as, their effects on stem cell differentiation and neurogenesis. L1 is a repetitive DNA retrotransposon, which can duplicate by a copy-and-paste genetic mechanism. The insertion could occur at any location including intragenic regions, which would alter the dynamics of the neuronal transcriptome by changing the expression pattern of nearby genes. Generally, these L1 insertions are kept quiescent by DNA methylation, except in developing neurons, wherein the frequency of L1 activity has been reported to be high compared to other tissues. Malav’s work will investigate the effects of food-derived opioid peptides on LINE-1 methylation levels, which indirectly correlates with the L1 activity. Malav will also be a core member of an international collaboration with investigators at Oxford University in the United Kingdom, participating in clinical studies investigating the effects of food-derived peptides on cognitive function.
Malav’s research project was previously funded by the Autism Research Institute and the National Institute of Drug Abuse.