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Section on Molecular Neurobiology

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About the Chief

Dr. De-Maw Chuang is the Chief of the Molecular Neurobiology Section of the Intramural Research Program, National Institute of Mental Health, National Institutes of Health at Bethesda, Maryland. He received his Ph.D. degree from the Molecular and Cellular Biology Program, State University of New York at Stony Brook, and did his postdoctoral training at the Roche Institute of Molecular Biology at Nutley, New Jersey.

Dr. Chuang is interested in translational research related to the mechanisms and implications of neuronal apoptosis in neurodegenerative and neuropsychiatric disorders. His research focuses on the neurobiology of mood stabilizing drugs, notably lithium and valproic acid. His laboratory is one of the first to demonstrate the neuroprotective and neurotrophic effects of mood stabilizers. He is expanding his previous work to investigate novel targets and actions of these drugs in several animal models of neurodegenerative and neuropsychiatric disorders. His goal is to demonstrate that mood stabilizers have additional uses in treating neurodegenerative/neuropsychiatric disorders.

Publications

Yu F, Wang Z, Tchantchou F, Chiu C-T, Zhang Y and Chuang D-M: Lithium ameliorates neurodegeneration, suppresses neuroinflammation and improves behavioral performance in a mouse model of traumatic brain injury. J Neurotrauma 29: 362-374, 2012. <view>

Tsai L-K, Wang Z, Munasinghe J, Leng Y, Leeds P and Chuang D-M: Mesenchymal stem cells primed with valproate and lithium robustly migrate to infarcted region and facilitate recovery in a stroke model. Stroke 42: 2932-2939, 2011. <view>

Wang Z, Leng Y, Leeds P and Chuang D-M: Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition. J Cerebral Blood Flow & Metabolism 31: 52-57, 2011. <view>

Omata N, Chiu C-T, Moya PR, Leng Y, Wang Z, Hunsberger JG, Leeds P and Chuang D-M: Lentivirally mediated GSK-3β silencing in the hippocampal dentate gyrus induces antidepressant-like effects in stressed mice. Intl J Neuropsychopharmacol 14: 711-717, 2011. <view>

Chiu C-T and Chuang D-M: Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of brain disorders. Pharmacol & Therapeut 128: 281-304, 2010. <view>

Tsai L-K, Leng Y, Wang Z, Leeds P and Chuang D-M: The mood stabilizers valproic acid and lithium enhance mesenchymal stem cell migration via distinct mechanisms. Neuropsychopharmacol 35: 2225-2237, 2010. <view>

Marinova Z, Ren M, Wendland J, Leng Y, Liang M-H, Yasuda S, Leeds P and Chuang D-M: Valproic acid induces functional heat-shock protein 70 via Class I histone deacetylase inhibition in cortical neurons: a potential role of Sp1 acetylation. J Neurochem 111: 976-987, 2009. <view>

Chuang D-M, Leng Y, Marinova Z, Kim HJ and Chiu C-T: Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends in Neurosci 32: 591-601, 2009. <view>

Kim HJ, Leeds P and Chuang D-M: The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain. J Neurochem 110: 1226-1240, 2009. <view>

Yasuda S, Liang M-H, Marinova Z, Yahyavi A and Chuang D-M: The mood stabilizers lithium and valproate selectively activate promoter IV of brain-derived neurotrophic factor in neurons. Mol Psychiatry 14: 51-59, 2009. <view>

Leng Y, Liang M-H, Ren M, Marinova Z, Leeds P and Chuang D-M: Synergistic neuroprotective effects of lithium and valproic acid or other HDAC inhibitors in neurons: Roles of GSK-3 inhibition. J Neurosci 28: 2576-2588, 2008. <view>

Kim Y-R, van Meer MPA, Tejima E, Murata Y, Mandeville JB, Dai G, Chuang D-M, Rosen BR and Lo EH: fMRI of delayed chronic lithium treatment in rat focal cerebral ischemia. Stroke 39: 439-447, 2008. <view>

Chuang D-M and Manji HK: In search of the holy grail for the treatment of neurodegenerative disorders: Has a simple cation been overlooked? Biol Psychiatry 62: 4-6, 2007. <view>

Kim, HJ, Rowe M, Ren M, Hong J-S, Chen P-S and Chuang D-M: Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action. J Pharmacol Exp Ther 321: 892-901, 2007. (Highlighted in Nature Reviews Drug Discovery, 6: 520, 2007). <view>

Liang M-H and Chuang D-M: Regulation and function of glycogen synthase kinase-3 isoforms in neuronal survival. J Biol Chem 282: 3904-3917, 2007. <view>

Liang M-H and Chuang D-M: Differential roles of glycogen synthase kinase-3 isoforms in the regulation of transcriptional activation. J Biol Chem 281: 30479-30484, 2006. <view>

Chen P-S, Peng G-S, Li G, Yang S, Wu X, Wang C-C, Wilson B, Lu R-B, Gean P-W, Chuang D-M and Hong J-S: Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol Psychiatry 11: 1116-1125, 2006. <view>

Chuang D-M and Priller J: Potential use of lithium in neurodegenerative disorders. In: M Bauer, P Grof and B Müller-Oerlingausen (eds): Lithium in Neuropsychiatry: The Comprehensive Guide. Taylor & Francis Books Ltd., London, UK, 2006, pp 381-397. <view>

Leng Y and Chuang D-M: Endogenous ±-synuclein is induced by valproic acid through histone deacetylase inhibition and participates in neuroprotection against glutamate-induced excitotoxicity. J Neurosci 26: 7502-7512, 2006. (Highlighted in Nature Medicine, 12: 893, 2006). <view>

Chuang D-M, Hough C and Senatorov VV: Glyceraldehyde-3-phosphate dehydrogenase, apoptosis and neurodegenerative diseases. Ann Rev Pharm Tox 45: 269-290, 2005. <view>

Chuang D-M: Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases? In "Mechanisms of Synaptic Plasticity: A Tribute to Mimo Costa". Crit Rev Neurobiol 16: 83-90, 2004. <view>

Ren M, Leng Y, Jeong M-R, Leeds PR and Chuang D-M: Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction. J Neurochem 89: 1358-1367, 2004. <view>

Senatorov VV, Ren M, Kanai H, Wei H and Chuang D-M: Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, a model of Huntington's disease. Mol Psychiatry 9: 371-385, 2004. <view>

Ren M, Senatorov VV, Chen R-W and Chuang D-M: Post-insult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model. Proc Natl Acad Sci USA 100: 6210-6215, 2003. (Received citations from Lead Discovery/Therapeutic Advances and News Feature of Nature, pp 118-120, September 11, 2003). <view>

Chuang D-M and Hough C: Neuroprotection against apoptosis: what has it got to do with the mood stabilizer lithium? In: Y-F Shi, J Cidlowski, D Scott, J Wu and Y-B Shi (eds): Molecular Mechanisms of Programmed Cell Death, Kluwer Academic/Plenum Publishers: New York, 2003, pp 145-154. <view>

Hashimoto R, Hough C, Nakazawa T, Yamamoto T and Chuang D-M: Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. J Neurochem 80: 589-597, 2002. (Received citation from News Feature of Nature, pp 118-120, September 11, 2003). <view>

Chuang D-M, Chen R-W, Chalecka-Franaszek E, Ren M, Hashimoto R, Senatorov V, Kanai H, Hough C, Hiroi T and Leeds P: Neuroprotective effects of lithium in cultured cells and animal models of diseases. Bipolar Disorders 4: 129-136, 2002. <view>

Chen R-W, Saunders PA, Wei H, Li Z, Seth P and Chuang D-M: Involvement of GAPDH and p53 in neuronal apoptosis: Evidence that GAPDH is upregulated by p53. J Neurosci 19: 9654-9662, 1999. <view>

Qin Z-H, Wang Y, Chen R-W, Nakai M, Chuang D-M and Chase TN: NF-kB nuclear translocation up-regulates c-Myc and p53 expression during N-methyl-D-aspartate receptor-mediated apoptosis in rat striatum. J Neurosci 19: 4023-4033, 1999. <view>

Chalecka-Franaszek E and Chuang D-M: Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci USA 96: 8745-8750, 1999. <view>

Chen R-W and Chuang D-M: Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression: a prominent role in neuroprotection against excitotoxicity. J Biol Chem (Communication) 274: 6039-6042, 1999. <view>