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Chitra Mandyam, Ph.D.

Associate Professor Adjunct
Department of Neuroscience
California Campus
Laboratory Website
Scripps VIVO Scientific Profile
cmandyam@scripps.edu
(858) 784-9039

Other Joint Appointments

Assistant Adjunct Professor, Skaggs school of pharmacy and pharmaceutical sciences, UCSD
Member, Graduate program in neurosciences, UCSD

Research Focus

The ability of the mammalian brain (including humans) to endlessly generate new precursor cells (stem and/or progenitor cells) throughout adulthood that maintain the structure and function of the brain changed the dogma that new glia and/or neurons were born only during development. Emerging research has demonstrated that the new phenomena "adult neurogenesis – the persistence of the entire process of neuronal development throughout adulthood” occurs in several brain regions including the medial prefrontal cortex (mPFC) and hippocampal subgranular zone (SGZ). Progenitors born in the mPFC are mostly gliogenic (oligodendrocytes) and those born in the SGZ are mostly neurogenic. Notably, the mPFC and hippocampus are involved in important stages of drug abuse. For example, the PFC has been implicated in several neurobiological phenomena associated with compulsive drug-seeking, and the hippocampus is implicated in forming context-specific memories associated with reinstatement of drug-seeking. Such roles associated with compulsive drug-seeking and context-specific memories may be hypothesized to involve gliogenic and neurogenic mechanisms. The focus of our laboratory is to determine if and how newly born cells in the mPFC and SGZ are affected by drugs of abuse.

Compulsive intake or escalation of intravenous drug self-administration is observed in rodents with extended access to many drugs of abuse. Therefore, intravenous self-administration holds significant clinical relevance and may provide a useful approach to understanding the neurobiological mechanisms responsible for the transition from drug use to escalation in intake. Importantly, the voluntary behavioral paradigm for compulsive drug intake may represent a particularly suitable model for testing the hypothesis that alteration in adult brain plasticity (such as gliogenesis and neurogenesis) by the drug is partly responsible for the addictive behavior.

We have recently shown that methamphetamine self-administration (a highly abused drug in the Southern California region with street names such as speed, meth, chalk, ice, crystal, glass) decreases gliogenesis in the adult rodent mPFC and neurogenesis in the adult rodent SGZ. Ongoing research in our laboratory will determine the underlying cellular and molecular mechanisms contributing to methamphetamine-induced decreases in cortical and hippocampal plasticity. Comprehension of how psychostimulants such as methamphetamine act to inhibit new precursors or progenitors in the adult brain will likely shed light on the basic mechanisms regulating adult neural stem cells. Our findings will improve our understanding of the complex mechanisms by which psychostimulants affect brain function and may help generate better therapies to treat methamphetamine addiction.

Education

M.S., Microbiology, Bangalore University, 1995
Ph.D., Neuropharmacology, University of Houston, 2002

Professional Experience

2016-2017 Associate Professor Adjunct, Committee on the Neurobiology of Addictive Disorders (CNAD), The Scripps Research Institute
2013-2016 Associate Professor, Committee on the Neurobiology of Addictive Disorders (CNAD), The Scripps Research Institute
2007-2013 Assistant Professor, Committee on the Neurobiology of Addictive Disorders (CNAD), The Scripps Research Institute
2005-2007 Research Associate, The Scripps Research Institute

Awards & Professional Activities

National Scholarship, Government of Karnataka, India (1988)
Pre-doctoral National Research Service Award, National Institute on Drug Abuse (2001)
Travel Award (International Narcotics Research Conference), National Institute on Drug Abuse (2001)
Graduate Student Research Achievement Award, University of Houston, Sigma Xi chapter (2001)
Travel Award (Route28 summits in neurobiology), VolkswagenStiftung (2002)
Post-doctoral National Research Service Award, National Institute on Drug Abuse (2003)
Poster Presentation Award in Neurosciences, Society of Fellows, The Scripps Research Institute (2006)
Mentored Research Career Development Award, National Institute on Drug Abuse (2007-2012)

Selected References

All Publications

Mandyam CD, Altememi GF, Standifer KM (2000) b-funaltrexamine inactivates ORL1 receptors in BE(2)-C human neuroblastoma cells. Eur J Pharmacol. Aug 18;402(1-2):R1-3.

Mathis JP, Mandyam CD, Altememi GF, Pasternak GW, Standifer KM (2001) OrphaninFQ/Nociceptin and Naloxone Benzoylhydrazone activate distinct receptors in BE(2)-C human neuroblastoma cells.  Neurosci Lett. Feb 23;299(3):173-176.

Mandyam CD, Thakker DR, Christensen JL and Standifer KM (2002) Orphanin FQ/Nociceptin (OFQ/N)-mediated desensitization of ORL1 and m opioid receptors involves PKC: a molecular mechanism for heterologous cross-talk. J Pharmacol Exp Ther, Aug;302(2):502-509.

Mandyam CD, Thakker DR and Standifer KM (2003) Mu opioid-induced desensitization of ORL1 and mu opioid receptors: Differential intracellular signaling determines receptor sensitivity. J Pharm Exp Ther, Sep; 306(3):965-972.

Eisch AJ and Mandyam CD (2004) Adult neurogenesis and drug abuse. Am J Psychiatry, March, 161:3.

Mandyam CD, Norris RD and Eisch AJ (2004) Chronic morphine induces premature mitosis of proliferating cells in the adult mouse subgranular zone. J Neurosci Res., Jun 15;76(6):783-94.

Richardson HN, Zorrilla EP, Mandyam CD and Rivier CL (2006) Exposure to repetitive versus varied stress during prenatal development generates two distinct anxiogenic and neuroendocrine profiles in adulthood. Endocrinology May;147(5):2506-17.

Battiste J, Helms AW, Kim EJ, Savage TK, Lagace DC, Mandyam CD, Eisch AJ, Miyoshi G, Johnson JE (2007) Ascl1 defines sequentially generated lineage-restricted neuronal and oligodendrocyte precursor cells in the spinal cord. Development. Jan;134(2):285-93.

Mandyam CD, Harburg GC, Eisch AJ (2007) Determination of key aspects of precursor cell proliferation, cell cycle length and kinetics in the adult mouse subgranular zone. Neuroscience. Apr 25;146(1):108-22.

Thakker DR, Altememi GF, Mandyam CD, Ibrahim H, Ramirez VI and Standifer KM. (2007) Naloxone benzoylhydrazone activates extracellular signal-regulated protein kinases and modulates nociceptin opioid peptide receptor specificity. Am J Pharm Toxicol, 2(2):51-59.

Eisch AJ and Mandyam CD. (2007) Neural progenitors: Can analysis of endogenous cell cycle markers move us “beyond BrdU”? In special issue “Analysis of progenitor cells in the brain before and after treatment." Current Pharmaceutical Biotechnology, Jun;8(3):147-65.

Mandyam CD, Wee S, Eisch AJ, Richardson HN and Koob GF (2007) Methamphetamine self-administration and voluntary exercise have opposing effects on medial prefrontal cortex gliogenesis. J Neurosci 27(42):11442-50.

Lagace DC, Whitman MC, Ables JL, DeCarolis NA, Noonan MA, Arguello AA, Donovan MH, Fischer SJ, Farnbauch LA, Beech RD, DiLeone RJ, Greer CA, Mandyam CD, Eisch AJ (2007) Nestin expression is coincident with neuronal fate in postnatal neurogenic regions. J Neurosci 27(46):12623-29.

Bawa-Khalfe T, Altememi GF, Mandyam CD, Eikenburg DC, Schwarz LA and Standifer KM (2007) The presence of beta 2-adrenoceptors sensitizes alpha 2A-adrenoceptors to desensitization after chronic epinephrine treatment. BMC Pharmacol. Dec 20, 7(1):16.

Wee S, Mandyam CD, Lekic DM, Koob GF (2008) A Role for the Alpha1-Noradrenergic System in the Bed Nucleus of Stria Terminalis in Increased Motivation for Cocaine Intake with Prolonged Access in Rats.  Eur Neuropsychopharm. Apr;18(4):303-11

Mandyam CD, Crawford EF, Eisch AJ, Rivier CL and Richardson HN (2008) Stress experienced in utero abolishes most sexual dichotomies in neurogenesis, microenvironment, and cell death in the adult rat hippocampus. Dev Neurobiol. Apr;68(5):575-89

George O*, Mandyam CD*, Wee S, Koob GF (2008) Cocaine Dependence Leads to Long-Lasting Damages of the Prefrontal Cortex. * equal contribution, Neuropsychopharm Sep;33(10):2474-82.

Mandyam CD*, Wee S, Crawford EF, Eisch AJ, Richardson HN, Koob GF (2008) Varied Access to Intravenous Methamphetamine Self-Administration Differentially Alters Adult Hippocampal Neurogenesis. Biol Psychiatry. Dec 1;64(11):958-65. *Provided cover art for Journal volume.

Arguello AA, Harburg GC, Schonborn JR, Mandyam CD, Yamaguchi M, Eisch AJ (2008) Time course of morphine's effects on adult hippocampal subgranular zone reveals preferential inhibition of cells in S phase of the cell cycle and a subpopulation of immature neurons. Neuroscience. Nov 11;157(1):70-9.

Richardson HN, Chan SH, Crawford EF, Lee YK, Funk CK, Koob GF and Mandyam CD (2009) Permanent impairment of birth and survival of cortical and hippocampal proliferating cells following excessive drinking during alcohol dependence. Neurobiology of Disease Oct 1; 36 (1):1-10.

Taffe MA, Kotzebue RW, Crean RD, Crawford EF, Edwards S and Mandyam CD (2010) Long-lasting reduction in hippocampal neurogenesis by alcohol consumption in adolescent nonhuman primates. Proc Natl Acad Sci U S A.

Book chapters

Eisch AJ and Mandyam CD (2004) Beyond BrdU: basic and clinical implications for analysis of endogenous cell cycle proteins. In: Greer EV, editor. Focus on stem cell research. Nova Science. p 111–142.

Eisch AJ and Mandyam CD (2005) Adult neurogenesis and CNS cell cycle analysis: novel tools for exploration of the neural causes and correlates of psychiatric disorders. In: Janigro D, editor. The cell cycle in the central nervous system. Totowa, NJ: Humana. p 315–342.

Links

UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences

Neurosciences Graduate Program UCSD