Sankt-Petersburg State University, Russia, 1986 (Physiology)
Address: 4301 West Markham Street, Slot 515 Little Rock, AR 72205
In our laboratory we are using electrophysiological, behavioral and immunohistological techniques to study normal and pathological mechanisms of neuronal excitability and signaling. Currently there are two major directions of the research in the laboratory. The first direction is the study of early mechanisms of diabetic neuropathy and pain. Diffuse distal peripheral neuropathy is a common and devastating complication of diabetes. The etiology of this complication is not known, but it is becoming increasingly clear that systemic hyperglycemia is not the only factor determining progression of this disease. Our data confirm the pathogenic role of hyperglycemia and, importantly they suggest insulinopenia/insulin resistance as being another, and possibly more critical than hyperglycemia, trigger of neuropathology in diabetes. The second direction of the research in the laboratory is evaluation of the expression and physiological function of isoforms of the Na+,K+-ATPase in peripheral nervous system of vertebrate animals. Na+,K+-ATPase has several isoforms expressed in a tissue- and cell-type dependent manner. In humans, mutations in the gene coding for neuron-specific alpha3 isoform of the transporter associate with early onset dystonia Parkinsonism. Interpretation of this association is however difficult because neither mechanisms controlling expression nor physiological significance of expression of this isozyme has been determined. Relevant to this issue, our studies suggest that expression of alpha3 Na+,K+-ATPase in neurons is regulated by the neuronal target, and that it is a critical determinant of neuronal ability to discharge a high-frequency and prolonged series of action potentials.
Neurobiology of pain and diabetic neuropathy; Physiological roles of isoforms of Na+,K+-ATPase
Dobretsov, M., and J.R. Stimers Neuronal function and a3 isoform of the Na+,K+-ATPase. 2005 Frontiers in Bioscience 10: 2373-2396.
- Dobretsov M., Hastings S.L., Romanovsky D., Stimers, J.R. and Zhang, J.-M. 2003. Mechanical hyperalgesia in the models of systemic and local hyperglycemia. Brain Res. 960:167-176.
- Dobretsov M., Hastings, S.L., Sims, T.J., Stimers, J.R. and Romanovsky D. 2003. Stretch receptor-associated expression of a3 isoform of the Na+/K+-ATPase in rat peripheral nervous system Neuroscience,116: 1069-1080.
- Romanovsky D., Hastings S.L., Stimers J.R., and Dobretsov M. 2004. Relevance of hyperglycemia to early mechanical hyperalgesia in streptozotocin-induced diabetes. Journal of the Peripheral Nervous System9:62-69.
- Romanovsky D., Light K., Walker J., and Dobretsov M. 2005. Target-determined expression of a3 isoform of the Na+,K+-ATPase in the somatic nervous system of rat. Journal of Comparative Neurology 483:114-123.
- Dobretsov M. and Romanovsky D. 2006. “Clock-scan” protocol for image analysis. Am. J. Physiology – Cell Physiology, 291: C869-C879.
- Romanovsky, D., Cruz, N.F., Dienel, G.A., and Dobretsov M. 2006. Mechanical hyperalgesia correlates with insulin deficiency in normoglycemic streptozotocin-treated rats. Neurobiology of Disease, 24: 384-394.
- Romanovsky, D., Moseley, A., Mrak, R., Taylor, M., and Dobretsov, M. 2007. Phylogenetic preservation of alpha 3 Na,K-ATPase distribution in vertebrate peripheral nervous system. Journal of Comparative Neurology, 500:1106-1116.