Our research interests focus on the molecular and cellular basis of neural plasticity as it pertains to psychiatric disorders. One major goal of the lab is to identify and understand the role of neurotrophic growth factors in the adult brain. Alterations in these factors and their intracellular signaling pathways have been suggested to play an important role in many psychiatric illnesses including depression. These neurotrophins, in particular brain-derived neurotrophic factor (BDNF), and their receptors are being studied in conditional and inducible cell-type specific knockout mice, as well as with the use of viral technology, to elucidate their role in neuronal function and complex behavior. As a complementary approach, we are using primary neuronal cultures to elucidate the signaling pathways by which these growth factors may be producing their effects. A second major goal of the lab is to examine the role of transcriptional repression on synaptic function. This project is focused on examining functional alterations that occur in neurons following the loss of synaptic repression. This approach is being coupled with studies examining a specific transcriptional repressor, methyl-CpG-binding protein (MeCP2), that has been linked as the causative factor in the neurodevelopmental disorder, Rett Syndrome. We are currently characterizing MeCP2 knockout mice in a broad array of behavioral paradigms focusing on modeling autistic-like behavior, as well as functionally examining how the loss of MeCP2 contributes to the disease state.
RESEARCH INTERESTS
Development of Animal Models for Psychiatric Diseases
Role of Growth Factors in Depression
Elucidating the Role of MeCP2 in Mediating Autistic-like Behavior (autism)
Role of Transcriptional Repression in Neurons
RECENT PUBLICATIONS
Gemelli T, Berton O, Nelson E, Perroti LI, Jaenisch R, Monteggia LM, "Postnatal loss of MeCP2 in the forebrain is sufficient to mediate behavioral aspects of Rett Syndrome in mice" Biol Psychiatry, Epub Sept 28 2005
Monteggia LM, Luikart B, Barrot M, Nef S, Parada LF, Nestler EJ, "BDNF Conditional Knockouts Show Gender Differences in Depression Related Behaviors." Biological Psychiatry, 61(2):187-197, 2007
Hensler JG, Advani T, Monteggia LM, "Regulation of 5-HT1A receptor function in inducible BDNF knock-out mice following administration of corticosterone." Biological Psychiatry, Epub March 2 2007
Lippmann M, Bress A, Nemeroff CB, Plotsky PM, Monteggia LM, "Long Term Behavioral and Molecular Alterations Associated with Maternal Separation in Rats." European Journal of Neuroscience, 25(10):3091-3098, 2007
Mahgoub MA, Sara Y, Kavalali ET, Monteggia LM, "Reciprocal interaction of activity and 5-HT in regulation of CRE-dependent gene expression." J Pharmacol Exp Ther, 317(1):88-96, 2006
SIGNIFICANT PUBLICATIONS
Duman RS, Monteggia LM, "A Neurotrophic Model for Stress-Related Mood Disorders" Biol Psychiatry, 59(12):1116-1127, 2006
Berton, O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ, "Essential Role of BDNF in the Mesolimbic Dopamine Pathway in Social Defeat Stress" Science, 311:864-868, 2006
Monteggia LM, Barrot M, Powell C, Berton O, Galanis V, Nagy A, Greene RW, Nestler EJ, "Essential Role of BDNF in Adult Hippocampal Function and Depression" Proc Natl Acad Sci, 101(29):10827-10832, 2004
Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM, "Neurobiology of Depression" Neuron, 34(1):13-25, 2002
Nelson E, Kavalali ET, Monteggia LM, "MeCP2-dependent transcriptional repression regulates excitatory neurotransmission" Current Biology, 16:710-716, 2006
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