University of Southern California

USC Neuroscience

Christian J. Pike

Professor
Davis School of Gerontology

Research Topics

  1. Regulation of Alzheimer's disease pathogenesis
  2. The role of sex steroid hormones in Alzheimer's disease
  3. Relationships between obesity, type 2 diabetes, and Alzheimer's disease
  4. Signaling pathways regulating neuronal apoptosis and neuroprotection

Research Overview

Research in my lab is broadly focused on Alzheimer's disease (AD), with the general goals of elucidating factors that regulate AD pathogenesis and pursuing translational approaches that will be useful in the prevention and/or treatment of the disease. Our approach to investigating research questions involves the use of complementary cellular, biochemical and molecular techniques to analyze relationships in human tissues, wild-type and transgenic rodent models, and cultured cells.

A primary area of focus in my laboratory is the relationship between age-related loss of steroid hormones and the development of AD. For example, our research with postmortem human brain has helped to identify testosterone loss in aging men as a risk factor for AD. In rodent models, we observe that depletion of androgens accelerates development of AD-like neuropathology and increases neuronal vulnerability to toxic insult. Cell culture studies continue to identify the relevant underlying mechanisms for these androgen effects, including investigation of classic genomic actions (e.g., regulation of genes such as neprilysin) as well as activation of rapid cell signaling pathways (e.g., MAPK/ERK, CREB, PKC). In ongoing translational studies, we are building upon our basic science advances to develop specific therapeutic interventions that selectively activate protective androgen pathways (e.g., synthetic testosterone mimetics). Using this general research strategy, we are pursuing conceptually parallel basic science and translational projects to evaluate the interactions between estrogen and progesterone actions in the regulation of neurodegenerative cascades associated with AD.

A new area of research in the lab seeks to understand the relationships between obesity, type 2 diabetes, and AD. Recent epidemiological findings have identified obesity in middle age, and its downstream consequences metabolic syndrome and type 2 diabetes, as significant risk factors for the development of AD in old age. Our efforts are focused at understanding the mechanistic links between these conditions, including the interactive roles of adiposity, neuroinflammation, and age-related changes in testosterone and estrogen.

Contact Information

E-mail:
cjpike@usc.edu
Mailing Address:
University of Southern California
Davis School of Gerontology
3715 McClintock Avenue
Los Angeles, CA 90089-0191
Office Location:
GER 306C
Office Phone:
(213) 740-4205
Lab Location:
GER 304
Lab Phone:
(213) 740-8244
Fax:
(213) 740-4787

Education

  • BS, University of Southern California, 1985
  • PhD, University of California Irvine, 1994
  • Postdoctoral Fellow, University of California Irvine, 1995

Research Images

Selected Publications

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Barron AM, Rosario ER, Brown MA, Eltereifi R, and Pike CJ (2013) Sex-specific effects of high-fat diet on indices of metabolic syndrome in 3xTg-AD mice: Implications for Alzheimer's disease. PLoS ONE. In press.

Barron AM, Garcia-Segura LM, Caruso D, Jayaraman A, Lee JW, Melcangi RC, and Pike CJ (2013) Ligand for translocator protein reverses pathology in a mouse model of Alzheimer's disease. J Neurosci 33 (20): 8891-8897. -PubMed

Jayaraman A, Carroll JC, Morgan TE, Lin S, Zhao L, Arimoto JM, Murphy MP, Beckett TL, Finch CE, Brinton RD, and Pike CJ (2012) 17beta-Estradiol and progesterone regulate expression of beta-amyloid clearance factors in primary neuron cultures and female rat brain. Endocrinology 153 (11): 5467-5479. -PubMed

Rosario ER, Chang L, Head EH, Stanczyk FZ, Pike CJ (2011) Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer's disease. Neurobiol Aging. 32 (4): 604-613. -PubMed

Carroll JC, Rosario ER, Villamagna A, Pike CJ (2010) Continuous and cyclic progesterone differentially interact with estradiol in the regulation of Alzheimer-like pathology in female 3xTg-AD mice. Endocrinology. 2010 Jun;151(6):2713-22. -PubMed

Pike CJ, Carroll JC, Rosario ER, Barron AM (2009) Protective actions of sex steroid hormones in Alzheimer's disease. Front Neuroendocrinol. 30(2):239-258. -PubMed

Carroll JC, Rosario ER, Chang L, Stanczyk FZ, Oddo S, LaFerla FM, Pike CJ (2007) Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J Neurosci. 27(48):13357-1336.  -PubMed

Yao M, Nguyen TV, Pike CJ (2007) Estrogen regulates Bcl-w and Bim expression: role in protection against beta-amyloid peptide-induced neuronal death. J Neurosci. 27(6):1422-1433. -PubMed

Rosario ER, Carroll JC, Oddo S, LaFerla FM, Pike CJ (2006) Androgens regulate development of neuropathology in a triple transgenic mouse model of Alzheimer disease. J Neurosci. 26(51):13384-13389. -PubMed

Yao M, Nguyen TV, Pike CJ (2005) Beta-amyloid-induced neuronal apoptosis involves c-Jun N-terminal kinase-dependent downregulation of Bcl-w. J Neurosci. 25(5):1149-1158. -PubMed