The goal of my laboratory is to examine the role that mediators of developmental neuroplasticity play in adult neuroplasticity. Detailed description of ongoing research in the Eisch Laboratory can be found on our home page: http://www3.utsouthwestern.edu/eisch/home.html. In brief, my laboratory is pursuing this goal via three primary avenues of research:
1) Characterization of factors that regulate adult neurogenesis
New cells are born in the adult mammalian hippocampus throughout life, and evidence suggests that these new cells contribute to hippocampal structure and function. Drugs of abuse, such as opiates, THC, ethanol, and nicotine, are known to decrease the number of new hippocampal cells. We are exploring if all drugs of abuse, regardless of their mechanism of action, similarly alter adult hippocampal neurogenesis, and in delineating the cellular mechanisms underlie the ability of drugs of abuse to alter adult neurogenesis. For example, how do opiates alter the cell cycle of hippocampal progenitors? Do opiates act directly on the progenitors to alter the cell cycle, or do opiates alter hippocampal growth factors, and thus indirectly alter the cell cycle? We are using both traditional and novel approaches to cell cycle analysis to address these questions.
2) Identification of behavioral consequences of altered adult neurogenesis, and exploration of the causal relationship between altered neurogenesis and behavioral and cognitive deficits.
We have shown that chronic exposure to opiates decreases the number of new neurons in the adult rat brain. It is established that both human abusers of opiates and rats chronically exposed to opiates show cognitive deficits and poor performance on learning and memory tasks. Is the decrease in new neurons in rats exposed to opiates related to the poor performance on memory tasks? To this end, we use a wide variety of behavioral testing paradigms to probe the relationship between hippocampal function, drug exposure, and adult neurogenesis.
Clearly. the behavioral studies mentioned above, while important, are limited by the fact that "correlation does not mean causation". Ideally, one would be able to examine a normal adult rat on a variety of learning and memory tasks, then "turn off" adult neurogenesis and see whether the learning and memory ability of the animal has been compromised. To this end, we have developed a transgenic mouse system where we can independently manipulate adult neurogenesis and then assess hippocampal function.
3) Exploration of other mediators of developmental neuroplasticity, such as growth factors, in regards to their role in adult neuroplasticity.
Involvement of the growth factors in regulation of adult neurogenesis
We have also recently identified a number of growth factors and cytokines that are altered in specific brain regions after chronic exposure to drugs of abuse. Given the role that many growth factors play in regulating proliferation and differentiation of newly-born cells, we are very interested in pursing the role that these growth factors may play in regulating the alterations in adult hippocampal neurogenesis see after chronic exposure to drugs of abuse.
Involvement of the ventral midbrain in a depressive-like phenotype
We are also intrigued by the role of growth factors in psychiatric disorders, such as depression. We have data suggesting that the growth factor BDNF appears to be "depressive" in the ventral midbrain. This is in contrast to the "antidepressive" role that BDNF appears to play in other brain regions, such as the hippocampus. We are very interested whether BDNF in the ventral midbrain plays a role in learning, as is also suggested by our data. These studies are ongoing and are generously supported by the National Alliance for Research on Schizophrenia and Depression, and our recent work on this topic is in press in the journal Biological Psychiatry
RESEARCH INTERESTS
My research focuses on the role that mediators of developmental neuroplasticity play in adult neuroplasticity.
Inability of the brain to "adapt" may contribute to - or exacerbate - myriad psychiatric disorders.
The main mediators of neuroplasticity we study are new neurons in the adult brain, or adult neurogenesis, and growth factors.
To this extent, we study how chronic exposure to drugs of abuse regulate adult neurogenesis; the role of growth factors in depression and motivation, and the regulation of adult neurogenesis in an animal model of Alzheimer's Disease. For more on my laboratory's research, please visit the Eisch Lab Website at www3.utsouthwestern.edu/eisch/
Mandyam CD, Crawford E, Lee S, Eisch AJ, Rivier CL and Richardson HN, "Prenatal stress differentially impacts hippocampal immature neuron phenotype and microenvironment in adult male and female offspring." Developmental Neurobiology, In Press
Lagace DC, Fischer SJ, Eisch AJ., "Influence of gender and endogenous levels of estradiol on adult hippocampal neurogenesis in mice." Hippocampus, 17:175-180, 2007
Mandyam CD, Harburg GC and Eisch AJ, "Determination of key technical aspects of precursor detection and division in the adult mouse subgranular zone." Neuroscience, 146:108-122, 2007
32) Lagace DC, Whitman MC, Noonan MA, Ables JL, DeCarolis NA, Arguello AA, Donovan MH, Fischer SJ, Farnbauch LA, Beech RD, Dileone RJ, Greer CA, Mandyam CD, Eisch AJ., "Dynamic contribution of nestin-expressing stem cells to adult neurogenesis." The Journal of Neuroscience., 27:12623?12629, 2007
30) Krishnan V, Han M-H, Graham D, Berton O, Renthal W, Laplant Q, Graham A, Russo S, Lutter M, Lagace DC, Ghose S, Reister R, Tannous P, Green T, Neve R, Chakravarty S, Eisch AJ, Self DW, Lee F, Tamminga C, Cooper D, Gershenfeld H, Nestler EJ., "Molecular Mechanisms of Resilience in Brain Reward Regions." Cell, doi:10.1016:j.cell.2007.09.018, 2007
SIGNIFICANT PUBLICATIONS
Messer CJ, Eisch AJ, Carlezon WA, Whisler K, Shen L, Wolf DH, Westphal H, Collins F, Russell DS, Nestler EJ, "Role for GDNF in biochemical and behavioral adaptations to drugs of abuse" Neuron, 26:1-20, 2000
Eisch AJ, Barrot M, Schad CA, Self DW, Nestler EJ., "Opiates inhibit neurogenesis in the adult rodent dentate gyrus" Proceedings of the National Academy of Sciences, USA, 97:7579-7584, 2000
Lagace DC, Yee JK, Bolanos CA, Eisch AJ, "Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis." Biological Psychiatry, 60:1121-1130, 2006
Harburg GC, Hall FS, Harrist AV, Sora I, Uhl GR, Eisch AJ, "Knockout of the mu opioid receptor enhances survival of adult-generated hippocampal granule cell neurons." Neuroscience, 144:77-87, 2006
Noonan MA, Choi K-H, Self DW, Eisch AJ., "Withdrawal from cocaine self-administration enhances hippocampal neurogenesis, but normalizes proliferation and maturation of neural progenitors, in the adult dentate gyrus subgranular zone" The Journal of Neuroscience, 28:2516-26, 2008
Point and right click (click and hold for Mac users) your mouse onand select "Save this link (or target) as..." option to save the file to your local computer.
and select "Save this link (or target) as..." option to save the file to your local computer.