Alexander A. Mongin
National Academy of Sciences of Belarus
The overall goal of our work is to understand complex roles of glial cells in normal brain functioning and in neurological disorders.
The term ‘glia’ embraces all non-excitable, non-neuronal cells in the brain, including astrocytes, oligodendrocytes, and microglial cells. In the adult brain, these three classes of glia are responsible for homeostatic maintenance of extracellular milieu, regulation of blood flow, modulation and scaling of synaptic transmission, acceleration of neuronal signaling via myelination, and innate immune responses. Impaired activity of glial cells is an important factor in progression of many neurological conditions, such as stroke, epilepsy, multiple sclerosis, Alzheimer’s disease, and chronic pain.
Our ongoing research addresses several important questions:
(1) What is the impact of oxidative and nitrosative stress on neuronal signaling and viability? In this broad field, we are particularly interested in oxidative modifications of glial transport and metabolism of the major excitatory neurotransmitter, glutamate. Our current NIH-sponsored work is largely focused on stroke but is also applicable to chronic neurodegenerative disorders, such as multiple sclerosis and Alzheimer’s disease.
(2) How does oxidative and nitrosative stress trigger long-term suppression of glutamatergic neuronal signaling? According to our working hypothesis, pathological production of free radicals leads to chemical modifications of numerous presynaptic and postsynaptic proteins and suppression of synaptic communication. We use a variety of proteomics and biochemistry approaches to identify which proteins are damaged and what would be an effective approach for preventing loss of protein function.
(3) Why pathological swelling of glial cells is detrimental for brain viability? Excessive swelling of astrocytes is a common feature of traumatic brain injury, stroke, and epilepsy. In this work, we are seeking to establish molecular identity of the membrane channels which open in swollen glial cells and mediate excessive release of glutamate.
(4) What mechanisms are responsible for high proliferative potential of glial brain tumors? In this translational project, we use combination of pharmacological and molecular biology approaches to identify novel targets for treatment of glioblastoma multiforme (GBM). GBM is the most common and deadly primary brain tumor. This work is carried in collaboration with AMC neurosurgeon Dr. Yu-Hung Kuo and involves analysis of model cell lines and surgical GBM specimens.
More information may be obtained by contacting Dr. Mongin via email address above, reading our recent publications, or visiting lab web site.
- Rudkouskaya, A., Sim, V., Shah, A.A., Feustel, P.J., Jourd’heuil, D., and Mongin, A.A. (2010) Long-lasting inhibition of presynaptic metabolism and neurotransmitter release by protein S-nitrosylation. Free Radical Biol. Med. 49, 757-769.
- Abdullaev, I.F., Rudkouskaya, A., Mongin, A.A., and Kuo, Y.H. (2010) Calcium-activated potassium channels BK and IK1 are functionally expressed in human gliomas but do not regulate cell proliferation. PLoS ONE, 5, e12304.
- Harrigan, T.J., Abdullaev, I.F., Jourd’heuil, D., and Mongin, A.A. (2008). Activation of microglia with zymosan promotes glutamate release via volume-regulated anion channels: the role of NADPH oxidases. J. Neurochem. 106, 2449-2462.
- Haskew-Layton, R.E., Rudkouskaya, A, Jin, Y., Feustel, P.J., Kimelberg, H.K., and Mongin, A.A. (2008). Two distinct modes of hypoosmotic medium-induced release of excitatory amino acids and taurine in the rat brain in vivo. PLoS ONE, 3 (10), e3543.
- Mongin, A.A. (2007). Disruption of ionic and cell volume homeostasis in ischemia: the perfect storm (Invited Review). Pathophysiology 14, 183-193.
- Abdullaev, I.F., Rudkouskaya, A., Schools, G.P., Kimelberg, H.K., and Mongin, A.A. (2006) Comparison of pharmacological profiles of volume-dependent chloride currents and organic osmolyte release in primary cultured astrocytes. J. Physiol. (London) 572 677-689.
- Haskew-Layton, R.E., Mongin, A.A., and Kimelberg, H.K. (2005). Hydrogen peroxide potentiates volume-sensitive excitatory amino acid release via a mechanism involving Ca2+/calmodulin-dependent protein kinase II. J. Biol. Chem. 280, 3548-3554.
- Mongin, A.A. and Kimelberg, H.K. (2005). ATP stimulates anion channel-mediated organic osmolyte release from cultured rat astrocytes via multiple Ca2+-sensitive mechanisms. Am. J. Physiol. Cell Physiol. 288, C204-C213.