CONTACT INFORMATIONDepartment of Psychiatry
University of Illinois at Chicago
912 S. Wood Street (MC 913),
Chicago, IL 60612
Office Phone: 312-355-5534
ORIGINAL PUBLICATIONS IN PEER-REVIEWED JOURNALS
1973 Guidotti A, Costa E. Involvement of adenosine 3',5' monophosphate in the activation of tyrosine hydroxylase elicited by drugs. Science 179: 902 904.
1976 Gale K, Guidotti A. GABA mediated control of rat neostriatal tyrosine hydroxylase revealed by the use of intranigral muscimol. Nature 263: 691 693.
1977 Biggio G, Brodie BB, Costa E, Guidotti A. Mechanisms by which diazepam, muscimol and other drugs change the content of cGMP in cerebellar cortex. Proc Natl Acad Sci USA 74: 3592 3596.
1979 Costa E, Guidotti A. Molecular mechanisms in the receptor action of benzodiazepines. In Okun GR, Cho AK (eds) Ann Rev Pharmacol Toxicol 19: 531 545.
1985 Alho H, Costa E, Ferrero P, Fujimoto M, Cosenza-Murphy D, Guidotti A. Diazepam binding inhibitor: a neuropeptide located in selected neuronal populations of rat brain. Science 229: 179-182.
1989 Sprengel R, Werner P, Seeburg PH, Mukhin AG, Santi MR, Grayson DR, Guidotti A, Krueger KE. Molecular cloning and expression of cDNA encoding a peripheral-type benzodiazepine receptor. J Biol Chem 264: 20415 20421.
1998 Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci USA 95: 3239-3244.
2000 Guidotti A, Auta J, Davis JM, Dwivedi Y, DiGiorgi VD, Impagnatiello F, Pandey GN, Pesold C, Sharma R, Uzunov DP, Costa E. Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder. A postmortem brain study. Arch Gen Psych 57: 1061-1069.
2005 Veldic M, Guidotti A, Maloku E, Davis JM, Costa E. In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc Natl Acad Sci USA 102 2152-2157.
2007 Ruzicka W, Zhubi A, Veldic M, Grayson DR, Costa E, Guidotti A. (2007) Selective epigenetic alteration of layer I GABAergic neurons isolated from prefrontal cortex of schizophrenia patients using laser-assisted microdissection. Mol Psychiatry 12:385-397.
2009 Guidotti A, Dong E, Kundakovic M, Satta R, Grayson DR, Costa E. Characterization of the action of antipsychotic subtypes on valproate-induced chromatin remodeling. Trend Pharmacol 30:55-60
2011 Guidotti A, Auta J, Chen Y, Davis JM, Dong E, Gavin DP, Grayson DR, Matrisciano F, Pinna G, Satta R, Sharma RP, Tremolizzo L, Tueting P. Epigenetic GABAergic targets in schizophrenia and bipolar disorder. Neuropharmacology 60:7-8):1007-1016.
Alessandro Guidotti, M.D.
Scientific Director, Psychiatric Institute Distinguished Professor
Born August 15, 1936, Florence, Italy. Naturalized U.S. citizen, 1978. M.D., University of Florence, Italy, 1961. Visiting Scientist, Department of Pharmacology, Oxford University, United Kingdom, 1966. Professor of Pharmacology, Department of Pharmacology, University of Florence, Italy, 1968-70. Visiting Associate, Laboratory of Preclinical Pharmacology, NIMH, St Elizabeths Hospital, Washington, DC, 1970-72. Acting Chief, 1973-75, and Chief, 1975-85. Section on Neuroendocrinology, Laboratory of Preclinical Pharmacology, NIMH, St Elizabeths Hospital, Washington DC. Deputy Director, FIDIA-Georgetown Institute for the Neurosciences, Georgetown University, Washington DC, 1985-94. Director, Neuroscience Training Program, Georgetown University, 1992-94. Acting Director, Center for Neuropharmacology, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, 1994-96. Professor, Environmental Medicine, NYU Medical Center, 1995-96. Professor of Psychiatry and Biochemistry, UIC, Department of Psychiatry, Chicago IL, 1996—; Scientific Director, Psychiatric Institute, Department of Psychiatry, UIC, Chicago IL, 2003--; Commissioned Lieutenant, Italian Medical Corp, 1961-62. Fellowship, National Italian Research Council, 1964-65. Privat Docent in Pharmacology, Italian Ministry of Education, 1968. Visiting Scientist, NIMH, 1970-72. Member of the American Society for Pharmacology and Experimental Therapy, 1973. Society for Neuroscience, 1973. International Society for Psychoneuroendocrinology, 1974. International Society of Neurochemistry, 1980. American College of Neuropsychopharmacology, 1989. Collegium Internationale Neuro-Psychopharmacologicum, 1989. American Society of Neurochemistry, 1993, Distinguished Professors, University of Illinois at Chicago, 2011.
In the 1970s, Guidotti demonstrated that the trans-synaptic induction of tyrosine-hydroxylase depends on the nuclear translocation of protein-kinaseA catalytic subunits and the phosphorylation of specific nuclear proteins (1).
Together with Costa (1975), he reported that benzodiazepines, allosterically acting at specific GABAA receptor sites, enhance GABA’s gating of Cl- channels (3,4). Pursuing this research trend, he discovered imidazenil, an imidazo-benzodiazepine acting as a selective positive allosteric modulator at GABAA receptors. Unlike other benzodiazepines, imidazenil is devoid of tolerance or dependence liabilities and may become the drug of choice to treat psychoses associated with GABAergic dysfunction (4-6). He also discovered (1990s) that SSRIs preferentially facilitate GABA's action at GABAA receptors by increasing brain neurosteroid content with potency greater than 5HT-reuptake inhibition (7).
Guidotti and his co-investigators (1998-2000) pioneered studies on the role of reelin in human cortex. Reelin is synthesized and secreted from GABAergic neurons into the extracellular matrix. He demonstrated that reelin acting at integrin receptors facilitates the translation of mRNAs located in dendrites of cortical pyramidal neurons (8). In cortical GABAergic neurons of schizophrenia patients, reelin and GAD67 expressions are downregulated (8), very likely by epigenetic promoter hypermethylation (9-12) related to high-order chromatin remodeling dysfunctions. Guidotti and collaborators recently discovered that valproate, an effective coadjuvant in psychosis treatment, inhibits brain chromatin histone deacetylases and promotes histone tail acetylation thereby downregulating methylation of promoters expressed by cortical GABAergic neurons (11). He proposes that demethylation of promoters expressed in GABAergic neurons could be a mechanism operative in the antipsychotic action of valproate (11,12).
Dr. Pandey is the recipient of the following awards:
- Researcher of the Year Award (awarded for his contribution to the understanding of the neurobiology of suicide) from the American Foundation for Suicide Prevention, 2010
- Bachawat Memorial Lifetime Achievement Award in Neuroscience from the Indian Academy of Neurosciences, 2010.
- UIC Researcher of the Year Award for the Clinical Sciences, 2010
- Science Congress President Gold Medal for excellence in Scientific Research presented by the Prime Minister of India, Dr. Manmohan Singh, at the 98th Indian Science Congress, held at the SRM University in Chennai, India, 2011
- Fellow - American College of Neuropsychopharmacology (ACNP), Fellow - Collegium Internationale Neuropsychopharmacologicum (CINP), Vice President - Indian Academy of Neurosciences (IAN)
- Member: American Society of Pharmacology and Experimental Therapy, Society of Biological Psychiatry, Society for Neuroscience, International Society for Neurochemistry, American Society for Neurochemistry, International Academy of Suicide Research.
- Member of the Editorial Board, International Journal of Neuropsychopharmacology
Neurobiology of adult and pediatric mood disorders and suicide
- Role of signal transduction mechanisms in mood disorders and suicide
- Role of neuroendocrine mechanisms and stress in mood disorders and suicide
- Role of neuroinflammatory mechanisms in in mood disorders and suicide