Kevin Noguchi, PhD
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 Farber and Wozniak labs, focuses on drug-induced neuropathology the immature brain. Due to the intricate ontogenetic processes that occur during brain development, drugs that are normally safe in the adult can be extremely toxic to the immature brain.
Much of this research is based on the ability of anesthetics and related drugs to produce apoptosis (programmed cell death) in the developing brain. This work is primarily based on the pioneering research done by my mentor, Professor John Olney (recently deceased), who I have worked closely with and plan to continue his research. Using animal models, we have found anesthetics are relatively safe in the adult but can be highly toxic to the developing brain. This suggests anesthesia may have adverse effects for over a million children that are exposed to anesthesia every year. This concept has recently been bolstered by several retrospective clinical studies showing children exposed to anesthesia exhibit neurodevelopmental impairment. However, it is important to acknowledge that anesthesia is oftentimes an important and necessary component of perinatal medicine. Therefore, we are characterizing when the developing brain is susceptible to this toxicity and working on safer ways to administer anesthesia. Unfortunately, these neurotoxic effects also occur in other drugs pharmacologically similar to anesthetics. These include drugs of abuse (such as alcohol, phencyclidine, and ketamine), sedatives, and anti-epileptic drugs. Therefore, we are also working to characterize the toxicity produced by these other drugs.
I also study the neurotoxic effects of glucocorticoids in the developing brain. Approximately, 10% of prematurely born infants receive glucocorticoid therapy to treat respiratory dysfunction associated with premature birth. Unfortunately, clinical research has found that this exposure can cause permanent neuromotor and cognitive deficits and selective cerebellar stunting. We have found that acute glucocorticoid exposure in the immature rodent produces rapid apoptosis (programmed cell death) in the neural progenitor cells of cerebellar external granule layer and permanent stunting of the cerebellum. As a result, this toxicity may explain many of the behavioral deficits associated with glucocorticoid therapy. Like anesthesia, glucocorticoids are oftentimes an important and necessary part of appropriate perinatal medicine. Therefore, we are also working on safer ways to administer this treatment.
Noguchi KK (2014 Jan 8). Glucocorticoid Induced Cerebellar Toxicity in the Developing Neonate: Implications for Glucocorticoid Therapy during Bronchopulmonary Dysplasia. Cells. 3(1): 36-52. Full Article ->
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 ->
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 SE, Noguchi KK, Wozniak DF, Fowler SC, Farber NB (2011 Dec 30). Long-term Effects of Multiple Glucocorticoid Exposures in Neonatal Mice. Behav Sci (Basel). 1(1): 4-30. Full Article ->
Cabrera O, Dougherty J, Singh S, Swiney BS, Farber NB, Noguchi KK (2013 Dec 19). Lithium protects against glucocorticoid induced neural progenitor cell apoptosis in the developing cerebellum. Brain Res. Full Article ->
Funded Research Projects
K01 NIMH(PI): Glucocorticoid and stress induced cerebellar neural progenitor cell apoptosis
R01 NICHD(PI:): Anesthesia toxicity in neonatal primate brain
KADRC Pilot Grant NIA(PI): Selective Glucocorticoid Receptor Modulation in Alzheimer's Disease