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Kevin Noguchi, PhD
Current
Position
Research Assistant Professor of Psychiatry
Education and Training
B.S. Biopsychology, University of California, Santa Barbara
M.A. Behavioral Neuroscience, University of California, Los Angeles
C. Phil. Behavioral Neuroscience, University of California, Los Angeles
Ph.D. Behavioral Neuroscience, University of California, Los Angeles
Areas of Research Interests
My research, in collaboration with the Olney and Farber labs, focuses on the neuropathology produced by glucocorticoids in the immature brain. Approximately, 7-10% of pregnant women and 10% of prematurely born infants receive glucocorticoid therapy to treat respiratory dysfunction associated with premature birth. Unfortunately, recent clinical research has found that postnatal exposure to this therapy can cause permanent neuromotor and cognitive deficits and prenatal exposure can produce decreased weight, length, and head circumference (a proxy measurement for brain size). Despite these concerns and the large percentage of the humans exposed to this hormone, surprisingly little is known about the endogenous role glucocorticoid exposure plays in normal neurodevelopment and how perinatal glucocorticoid therapy may lead to brain maldevelopment.
My research has found that acute glucocorticoid exposure in the immature rodent produces rapid apoptotic cell death in the neural progenitor cells of cerebellar external granule layer and permanent decreases in number of granule cells in the internal granule layer. We have also estimated that an equivalent human window of vulnerability for this toxicity would include all perinatal periods during which glucocorticoid therapy is administered. Since the cerebellum is associated with many of the behavioral deficits seen in prematurely born neonates exposed to glucocorticoid therapy, this toxicity may provide a mechanism through which perinatal glucocorticoid therapy can produce its detrimental effects on the developing human brain .
More recently, my research has focused on whether 11B-Hydroxysteroid Dehydrogenase Type II (an enzyme selectively located in the external granule layer) might provide a natural defense against this toxicity by metabolizing certain types of glucocorticoids before they can produce this degeneration. If true, it would suggest glucocorticoids which this enzyme can metabolize (and are not commonly used clinically) might treat perinatal respiratory dysfunction but not be as toxic.
I am additionally examining the possible neurodevelopmental role of glucocorticoids in cerebellar development. I believe that the natural stimulation from endogenous glucocorticoids is a maturational signal to delete these progenitor cells once their job of producing new neurons is over. This would explain why exogenous administration of glucocorticoids would cause such a selective toxicity. It would also suggest that when glucocorticoids are administered perinatally they iatrogenically induce the premature death of these cells thereby disrupting normal cerebellar development.
Finally, while my focus is primarily on glucocorticoid induced toxicity, I continue to hold interests in my early work examining the neuropathology produced by drugs of abuse.
Key Publications
Noguchi KK, Walls KC, Wozniak DF, Olney JW, Roth KA, Farber NB (2008 Oct). Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death. Cell Death Differ. 15(10): 1582-92. Full Article ->
Noguchi KK, Lau K, Smith DJ, Swiney BS, Farber NB (2011 Aug). Glucocorticoid receptor stimulation and the regulation of neonatal cerebellar neural progenitor cell apoptosis. Neurobiol Dis. 43(2): 356-63. Full Article ->
Noguchi KK, Nemmers B, Farber NB (2005 Aug 8). Age has a similar influence on the susceptibility to NMDA antagonist-induced neurodegeneration in most brain regions. Brain Res Dev Brain Res. 158(1-2): 82-91. Full Article ->
Hanslick JL, Lau K, Noguchi KK, Olney JW, Zorumski CF, Mennerick S, Farber NB (2009 Apr). Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system. Neurobiol Dis. 34(1): 1-10. Full Article ->
Maloney, S.E.*, Noguchi, K.K.*, Wozniak, D.F.*, Fowler, S.C., Farber, N.B. (2011) Long-term Effects of Multiple Glucocorticoid Exposures in Neonatal Mice. Behav. Sci. 1(1):4-30.
*Contributed equally to this work
http://www.mdpi.com/2076-328X/1/1/4/ Full Article ->
Funded Research Projects
NIMH(PI): Glucocorticoid and stress induced cerebellar neural progenitor cell apoptosis