Regretfully, Dr. Maharaj Ticku passed away unexpectedly on November 6, 2007. His research will continue to be carried out by other members of the Pharmacology faculty.
Dr. Ticku's major research goals are to understand and define the molecular mechanisms by which drugs modulate inhibitory and excitatory neurotransmitter systems in the mammalian central nervous system. GABAA and NMDA receptors belong to a ligand-gated super gene family. A major focus of our research is to determine the effect of chronic administration of benzodiazepines, barbiturates, neurosteroids or alcohol on regulation of GABAA receptor binding, function, gene and polypeptide expression. Chronic drug treatment could affect neurotransmission by down- or upregulation of receptors, altered coupling between various sites associated with oligomeric receptor complex and/or altered receptor efficacy. How alcohol regulates NMDA gene expression is a major focus. More recent research is aimed at establishing how chronic alcohol alters gene expression of NMDA receptors at the level of epigenetics, transcriptional factors, subsynaptic distribution and trafficking regulating proteins.
These experiments are being conducted in mammalian cortical neurons under precisely controlled conditions and independent of pharmacokinetic variability. A second focus is the investigation of the effects of alcohol on NMDA receptor function and gene expression. NMDA receptors are involved in a variety of physiological processes, including maintenance of excitability, neuronal development, learning and memory as well as in the pharmacological effects of alcohol. A number of different experimental approaches are employed in these studies including receptor binding, 36Cl-flux, changes in intracellular Ca+2 levels, mRNA and polypeptide level measurements. Current research involves regulation of promoter activity of NMDA R2B gene by enhancers and silencing factors (Mol Pharm papers, 2005).
More recent studies include developing new probes (agonists, antagonists) to study how the date rape drug (GHB) works in the brain. These drugs have potential to be used for GHB intoxication.
Research Associates
Currently, Drs. A.K. Mehta (Research Assistant Professor), Mei Qiang (Research Instructor), C.R.M. Ravindran (Postdoctoral Fellow), and Ms. Ashley Denny (Research Assistant) are working in Dr. Ticku's laboratory.
Societal Affiliations
Dr. Ticku is a member of many societies including ASPET; Society of Neuroscience; American college of Neuropsychopharmacology (ACNP); Research Society on Alcoholism; Collegium Internationale Neuro-Psychopharmacologicum (CINP); Society of Neurochemistry and ISBRA. He has chaired many national and international symposiums. Dr. Ticku's research has continuously been funded by NIH/NIAAA since 1979. Additionally, Dr. Ticku has served on NIH-NINDS and NIH-NIAAA study sections, and Chaired many Special Review Committees of NIAAA. He also served as a consultant to United Nations. Dr. Ticku is currently the recipient of a MERIT Award from NIH-NIAAA (2000-2010).
Selected Publications
Qiang, M., Denny, A.D., and Ticku, M.K. Chronic intermittent ethanol treatment selectively alters NMDA receptor subunits surface expression in cultured cortical neurons. Mol Pharmacol. 2007, April 17 (Epub ahead of print).
Ravindran, M., Mehta, C.R., and Ticku, M.K. Effect of chronic administration of ethanol on the regulation of tyrosine kinase phosphorylation of the GABA(A) receptor subunits in the rat brain. Neurochem Res. Jul;32(7):1179-87 (2007).
Wang, J., Gutala, R., Sun, D., Ma, J.Z., Sheela, R.C., Ticku, M.K., Li, M.D. Regulation of platelet-derived growth factor signaling pathway by ethanol, nicotine, or both in mouse cortical neurons. Alcohol Clin Exp Res. Mar;31(3):357-75 (2007).
Ravindran, C.R. and Ticku, M.K. Tyrosine kinase phosphorylation of GABA(A) receptor alpha1, beta2, and gamma2 subunits following chronic intermittent ethanol (CIE) exposure of cultured cortical neurons of mice. Neurochem Res. Sep31;(9):111-8 (2006).
Sheela Rani, C.S. and Ticku, M.K. Comparison of chronic ethanol and chronic intermittent ethanol treatments on the expression of GABA(A) and NMDA receptor subunits. Alcohol. Feb;38(2):89-97 (2006).
Marutha Ravindran, C.R. and Ticku, M.K. Tyrosine kinase phosphorylation of GABA(A) receptor subunits following chronic ethanol exposure of cultured cortical neurons of mice. Brain Res. May 1;1086(1):35-41 (2006).
Mehta, A.K., Gould, G.G., Gupta, M., Carter, L.P., Gibson, K.M., and Ticku, M.K. Succinate semialdehyde dehydrogenase deficiency does not down-regulate gamma-hydroxybutyric acid binding sites in the mouse brain. Mol Genet Metab. May;88(1):86-9 (2006).
Qiang, M., and Ticku, M.K. Role of Ap-1 in ethanol-induced N-methyl-D-aspartate receptor 2B subunit gene up-regulation in mouse cortical neurons. J Neurochem. Dec;95(5):1332-41 (2005).
Qiang, M., Rani, CS., and Ticku, MK. Neuron-restrictive silencer factor regulates the N-methyl-D-aspartate receptor 2B subunit gene in basal and ethanol-induced gene expression in fetal cortical neurons. Mol Pharmacol. 67:2115-2115, 2005.
Rani, CS., Qiang, M., and Ticku, MK. Role of cAMP response element-binding protein in ethanol-induced N-methyl-D-aspartate receptor 2B subunit gene transcription in fetal mouse cortical cells. Mol Pharmacol. 67:2126-2136, 2005.
Maratha, RCV and Ticku, MK. Role of CpG islands in the up-regulation of NMDA receptor NR2B gene expression following chronic ethanol treatment of cultured cortical neurons of mice. Neurochem Int. 46: 313-327, 2005.
Mehta, AK and Ticku, MK. Effect of chronic ethanol administration of ethanol on GABAA receptor assemblies derived from alpha-2, alpha3-., beta2--and gamma2 subunits in the rat cerebral cortex. Brain Res. 1031: 134-137, 2005.
Gutala, R., Wang, J., Kadapakkam, S., Hwang, Y., Ticku, M., and Li, MD. Microarray analysis of ethanol-induced cortical neurons reveals disruption of genes related to the ubiquitin-proteasome pathway and protein synthesis. Alcohol Clin Exp Res. 28: 1779-1788, 2004.
Marutha, RCR and Ticku, MK. Changes in methylation pattern of NMDA receptor NR2B gene in cortical neurons after chronic ethanol treatment in mice. Brain Res Mol Brain Res. 121: 19-27, 2004.
Tabish, M. and Ticku, MK. Alternate splice variants of mouse NR2B gene. Neurochem Int. 46: 1-9, 2004.
Kalluri, HS and Ticku, MK. Regulation of ERK phosphorylation by ethanol in fetal cortical neurons. Neurochem Res. 28: 765-769, 2003.
Mehta, AK., Muschweck, NM, Maeda, DY, Coop, A. and Ticku, M. K. Binding characteristics of the gamma-hydroxybutyric acid receptor antagonist [(3)H](2E)-(5-hydroxy-5, 7, 8, 9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene)ethanoic acid in the rat brain. J. Pharmacol Exp Ther. 299: 1148-1153, 2001.
Kumari M, Ticku, MK. Regulation of NMDA receptors by ethanol. Prog Drug Res. 54:152-89, 2000.
Mehta, A.K. and Ticku, M.K. An update on GABAA receptors, Brain Res. Rev. 29:196- 217, 1999 (Review).
Kalluri, H.S.G. and Ticku, M.K. Potential involvement of tyrosine kinase pathway in the antagonist induced upregulation of the NMDA receptor NR2B subunit in cortical neurons, Mol. Brain Res. 65:206-210, 1999.
Mehta, A.K. and Ticku, M.K. Prevalence of the GABAA receptor assemblies containing _1-subunit in the rat cerebellum and cerebral cortex as determined by immunoprecipitation: lack of modulation by chronic ethanol administration, Mol. Brain Res. 67:194-199, 1999.
Kalluri, H.S.G. and Ticku, M.K. Effect of ethanol on phosphorylation of the NMDAR2B subunit in mouse cortical neurons, Mol. Brain Res. 68:159-168, 1999.
Mehta, A.K. and Ticku, M.K. An investigation on the role of nitric oxide in the modulation of the binding characteristics of various radioligands of GABAA receptors by 5 _-pregnan-3__-o1-20-one in the rat brain regions, Brain Res. 832:164-167, 1999.
Kumari, M. and Ticku, M.K. Ethanol differentially regulates expression of the NMDA receptor subunits at the transcriptional and post-transcriptional level. J. Neurochem. 70:1467-1463, 1998.
Hu, X.-J. and Ticku, M.K. Functional characterization of a kindling-like model of ethanol withdrawal in cortical cultured neurons after chronic intermittent ethanol exposure. Brain Res. 767:228-234, 1997.
Sousa, A. and Ticku, M.K. Interactions of the neurosteroid dehydroepiandrosterone sulfate with the GABAA receptor complex reveals that it may act via the picrotoxin site. J. Pharmacol. Exp. Ther. 282:827-833, 1997.
Follesa, P. and Ticku, MK. Chronic ethanol-mediated upregulation of the NMDA receptor polypeptide levels in mouse cortical neurons in culture. J. Biol. Chem. 271:13297-13300, 1996.
