Cellular mechanisms of neuronal dysfunction

National Institute On Drug Abuse

Investigators

Linked publications & trials

Abstract

Using a the SERCaMP technology that we previously developed, we found that both a cafeteria diet and high fat diet cause ER calcium dysfunction in rat liver. The dysregulation of ER calcium is implicated in wide variety of disease states. Our findings provide a possible mechanism by which liver function is altered in response to excessive fat in the diet. Our findings our published in the Journal of Hepatology. Based on our SERCaMP technology, we developed a library to screen the human proteome for other C-terminal tails that may confer ER retention and release in response to ER calcium depletion. We identified the tail of an endogenous esterase that functions as a SERCaMP tail and we developed an assay to measure the esterase in the cell culture media and plasma from both humans and rodents. We published a paper describing this novel biomarker of ER calcium depletion in Biomarkers. We describe the characterization and development of multiple transgenic tools that express a near-infrared fluorescent protein (IRFP) in neurons as a reporter of transgene expression. The longer wavelength of light used for visualization offers many advantages over other fluorescent reporters used for neuroscience applications related to our work on the cellular mechanisms of neuronal dysfunction. This work was published in J Neuroscience Methods. In collaboration with Dr. Mikko Airavaara, we published two papers on potential post-stroke therapies. First, we showed that MANF promotes recovery from stroke when administered post-stroke (Sci Adv 2018). We also show that intranasal delivery of naloxone enantiomer was able to reduce stroke-related inflammation in the brain and promote recovery in rat model of stroke (eNeuro 2018). In collaboration with Kent Hamra, we developed a spermatogonial stem cell line from Long Evans rats to be used for generating transgenic rat lines.