Christian Pike, PhD

InstitutionUniversity of Southern California
Address3715 McClintock Ave., Suite 306D
University Park Campus
Los Angeles CA 90089-0191
Phone+1 213 740 4205
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    Collapse Biography 
    Collapse Awards and Honors
    Alzheimer's Association2000Turken Award

    Collapse Overview 
    Collapse 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.

    Collapse Research 
    Collapse Research Activities and Funding
    Sex differences in the relationship between APOE and AD: Role of sexual differentiation
    NIH/NIA RF1AG058068Sep 15, 2017 - Jun 30, 2022
    Role: Principal Investigator
    Interactions between Testosterone and Type 2 Diabetes in Alzheimer's Disease
    NIH/NIA R01AG034103Sep 1, 2011 - Aug 31, 2016
    Role: Principal Investigator
    Androgens and Alzheimer's Disease
    NIH/NIA R01AG023739Jan 1, 2005 - Dec 31, 2010
    Role: Principal Investigator
    NIH/NIA R01AG015961Feb 1, 2000 - Jan 31, 2005
    Role: Principal Investigator
    NIH/NIA R55AG015961Sep 30, 1998 - Jan 31, 2000
    Role: Principal Investigator

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Christensen A, Pike CJ. APOE genotype affects metabolic and Alzheimer-related outcomes induced by Western diet in female EFAD mice. FASEB J. 2018 Dec 03; fj201801756R. PMID: 30509127.
      View in: PubMed
    2. Moser VA, Uchoa MF, Pike CJ. TLR4 inhibitor TAK-242 attenuates the adverse neural effects of diet-induced obesity. J Neuroinflammation. 2018 Nov 05; 15(1):306. PMID: 30396359.
      View in: PubMed
    3. Moser VA, Christensen A, Liu J, Zhou A, Yagi S, Beam CR, Galea L, Pike CJ. Effects of aging, high-fat diet, and testosterone treatment on neural and metabolic outcomes in male brown Norway rats. Neurobiol Aging. 2018 Sep 22; 73:145-160. PMID: 30359877.
      View in: PubMed
    4. Yen K, Wan J, Mehta HH, Miller B, Christensen A, Levine ME, Salomon MP, Brandhorst S, Xiao J, Kim SJ, Navarrete G, Campo D, Harry GJ, Longo V, Pike CJ, Mack WJ, Hodis HN, Crimmins EM, Cohen P. Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans. Sci Rep. 2018 Sep 21; 8(1):14212. PMID: 30242290.
      View in: PubMed
    5. Christensen A, Pike CJ. TSPO ligand PK11195 improves Alzheimer-related outcomes in aged female 3xTg-AD mice. Neurosci Lett. 2018 Jun 17. PMID: 29925037.
      View in: PubMed
    6. Davies JMS, Cillard J, Friguet B, Cadenas E, Cadet J, Cayce R, Fishmann A, Liao D, Bulteau AL, Derbré F, Rébillard A, Burstein S, Hirsch E, Kloner RA, Jakowec M, Petzinger G, Sauce D, Sennlaub F, Limon I, Ursini F, Maiorino M, Economides C, Pike CJ, Cohen P, Salvayre AN, Halliday MR, Lundquist AJ, Jakowec NA, Mechta-Grigoriou F, Mericskay M, Mariani J, Li Z, Huang D, Grant E, Forman HJ, Finch CE, Sun PY, Pomatto LCD, Agbulut O, Warburton D, Neri C, Rouis M, Cillard P, Capeau J, Rosenbaum J, Davies KJA. The Oxygen Paradox, the French Paradox, and age-related diseases. Geroscience. 2017 12; 39(5-6):499-550. PMID: 29270905.
      View in: PubMed
    7. Moser VA, Pike CJ. Obesity Accelerates Alzheimer-Related Pathology in APOE4 but not APOE3 Mice. eNeuro. 2017 May-Jun; 4(3). PMID: 28612048.
      View in: PubMed
    8. Christensen A, Pike CJ. Age-dependent regulation of obesity and Alzheimer-related outcomes by hormone therapy in female 3xTg-AD mice. PLoS One. 2017; 12(6):e0178490. PMID: 28575011.
      View in: PubMed
    9. Pike CJ. Sex and the development of Alzheimer's disease. J Neurosci Res. 2017 01 02; 95(1-2):671-680. PMID: 27870425.
      View in: PubMed
    10. Uchoa MF, Moser VA, Pike CJ. Interactions between inflammation, sex steroids, and Alzheimer's disease risk factors. Front Neuroendocrinol. 2016 10; 43:60-82. PMID: 27651175.
      View in: PubMed
    11. Moser VA, Pike CJ. Obesity and sex interact in the regulation of Alzheimer's disease. Neurosci Biobehav Rev. 2016 08; 67:102-18. PMID: 26708713; PMCID: PMC4912955 [Available on 08/01/17].
    12. Cacciottolo M, Christensen A, Moser A, Liu J, Pike CJ, Smith C, LaDu MJ, Sullivan PM, Morgan TE, Dolzhenko E, Charidimou A, Wahlund LO, Wiberg MK, Shams S, Chiang GC. The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice. Neurobiol Aging. 2016 Jan; 37:47-57. PMID: 26686669; PMCID: PMC4687024 [Available on 01/01/17].
    13. Christensen A, Pike CJ. Menopause, obesity and inflammation: interactive risk factors for Alzheimer's disease. Front Aging Neurosci. 2015; 7:130. PMID: 26217222; PMCID: PMC4493396.
    14. Yin F, Yao J, Sancheti H, Feng T, Melcangi RC, Morgan TE, Finch CE, Pike CJ, Mack WJ, Cadenas E, Brinton RD. The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity. Neurobiol Aging. 2015 Jul; 36(7):2282-2295. PMID: 25921624; PMCID: PMC4416218.
    15. Barron AM, Brown MA, Morgan TE, Pike CJ. Impact of continuous versus discontinuous progesterone on estradiol regulation of neuron viability and sprouting after entorhinal cortex lesion in female rats. Endocrinology. 2015 Mar; 156(3):1091-9. PMID: 25514084; PMCID: PMC4330320.
    16. Jayaraman A, Lent-Schochet D, Pike CJ. Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function. J Neuroinflammation. 2014 Sep 16; 11:162. PMID: 25224590; PMCID: PMC4190446.
    17. Jayaraman A, Pike CJ. Alzheimer's disease and type 2 diabetes: multiple mechanisms contribute to interactions. Curr Diab Rep. 2014 Apr; 14(4):476. PMID: 24526623; PMCID: PMC3985543.
    18. Jayaraman A, Christensen A, Moser VA, Vest RS, Miller CP, Hattersley G, Pike CJ. Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats. Endocrinology. 2014 Apr; 155(4):1398-406. PMID: 24428527; PMCID: PMC3959610.
    19. Jayaraman A, Pike CJ. Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons. Mol Cell Endocrinol. 2014 Mar 25; 384(1-2):52-60. PMID: 24424444; PMCID: PMC3954450.
    20. Barron AM, Rosario ER, Elteriefi R, Pike CJ. Sex-specific effects of high fat diet on indices of metabolic syndrome in 3xTg-AD mice: implications for Alzheimer's disease. PLoS One. 2013; 8(10):e78554. PMID: 24205258; PMCID: PMC3810257.
    21. Barron AM, Garcia-Segura LM, Caruso D, Jayaraman A, Lee JW, Melcangi RC, Pike CJ. Ligand for translocator protein reverses pathology in a mouse model of Alzheimer's disease. J Neurosci. 2013 May 15; 33(20):8891-7. PMID: 23678130; PMCID: PMC3733563.
    22. Caruso D, Barron AM, Brown MA, Abbiati F, Carrero P, Pike CJ, Garcia-Segura LM, Melcangi RC. Age-related changes in neuroactive steroid levels in 3xTg-AD mice. Neurobiol Aging. 2013 Apr; 34(4):1080-9. PMID: 23122920; PMCID: PMC3545103.
    23. Jayaraman A, Carroll JC, Morgan TE, Lin S, Zhao L, Arimoto JM, Murphy MP, Beckett TL, Finch CE, Brinton RD, Pike CJ. 17ß-estradiol and progesterone regulate expression of ß-amyloid clearance factors in primary neuron cultures and female rat brain. Endocrinology. 2012 Nov; 153(11):5467-79. PMID: 22962256; PMCID: PMC3473201.
    24. Rosario ER, Carroll JC, Pike CJ. Evaluation of the effects of testosterone and luteinizing hormone on regulation of ß-amyloid in male 3xTg-AD mice. Brain Res. 2012 Jul 23; 1466:137-45. PMID: 22587890; PMCID: PMC3399667.
    25. Vest RS, Pike CJ. Gender, sex steroid hormones, and Alzheimer's disease. Horm Behav. 2013 Feb; 63(2):301-7. PMID: 22554955; PMCID: PMC3413783.
    26. Aras R, Barron AM, Pike CJ. Caspase activation contributes to astrogliosis. Brain Res. 2012 Apr 23; 1450:102-15. PMID: 22436850; PMCID: PMC3319728.
    27. Zhao L, Morgan TE, Mao Z, Lin S, Cadenas E, Finch CE, Pike CJ, Mack WJ, Brinton RD. Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. PLoS One. 2012; 7(2):e31267. PMID: 22393359; PMCID: PMC3290616.
    28. Barron AM, Pike CJ. Sex hormones, aging, and Alzheimer's disease. Front Biosci (Elite Ed). 2012 Jan 01; 4:976-97. PMID: 22201929; PMCID: PMC3511049.
    29. Aguirre C, Jayaraman A, Pike C, Baudry M. Progesterone inhibits estrogen-mediated neuroprotection against excitotoxicity by down-regulating estrogen receptor-ß. J Neurochem. 2010 Dec; 115(5):1277-87. PMID: 20977477; PMCID: PMC3010223.
    30. Carroll JC, Rosario ER, Kreimer S, Villamagna A, Gentzschein E, Stanczyk FZ, Pike CJ. Sex differences in ß-amyloid accumulation in 3xTg-AD mice: role of neonatal sex steroid hormone exposure. Brain Res. 2010 Dec 17; 1366:233-45. PMID: 20934413; PMCID: PMC2993873.
    31. Rosario ER, Carroll J, Pike CJ. Testosterone regulation of Alzheimer-like neuropathology in male 3xTg-AD mice involves both estrogen and androgen pathways. Brain Res. 2010 Nov 04; 1359:281-90. PMID: 20807511; PMCID: PMC2965035.
    32. Carroll JC, Rosario ER, Villamagna A, Pike CJ. Continuous and cyclic progesterone differentially interact with estradiol in the regulation of Alzheimer-like pathology in female 3xTransgenic-Alzheimer's disease mice. Endocrinology. 2010 Jun; 151(6):2713-22. PMID: 20410196; PMCID: PMC2875823.
    33. Rosario ER, Chang L, Beckett TL, Carroll JC, Paul Murphy M, Stanczyk FZ, Pike CJ. Age-related changes in serum and brain levels of androgens in male Brown Norway rats. Neuroreport. 2009 Nov 25; 20(17):1534-7. PMID: 19829160.
      View in: PubMed
    34. Nguyen TV, Yao M, Pike CJ. Dihydrotestosterone activates CREB signaling in cultured hippocampal neurons. Brain Res. 2009 Nov 17; 1298:1-12. PMID: 19729001; PMCID: PMC2775803.
    35. Rosario ER, Chang L, Head EH, Stanczyk FZ, Pike CJ. Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer's disease. Neurobiol Aging. 2011 Apr; 32(4):604-13. PMID: 19428144; PMCID: PMC2930132.
    36. Pike CJ, Carroll JC, Rosario ER, Barron AM. Protective actions of sex steroid hormones in Alzheimer's disease. Front Neuroendocrinol. 2009 Jul; 30(2):239-58. PMID: 19427328; PMCID: PMC2728624.
    37. Carroll JC, Rosario ER, Pike CJ. Progesterone blocks estrogen neuroprotection from kainate in middle-aged female rats. Neurosci Lett. 2008 Nov 21; 445(3):229-32. PMID: 18790007; PMCID: PMC2591925.
    38. Yao M, Nguyen TV, Rosario ER, Ramsden M, Pike CJ. Androgens regulate neprilysin expression: role in reducing beta-amyloid levels. J Neurochem. 2008 Jun 01; 105(6):2477-88. PMID: 18346198.
      View in: PubMed
    39. Brinton RD, Thompson RF, Foy MR, Baudry M, Wang J, Finch CE, Morgan TE, Pike CJ, Mack WJ, Stanczyk FZ, Nilsen J. Progesterone receptors: form and function in brain. Front Neuroendocrinol. 2008 May; 29(2):313-39. PMID: 18374402; PMCID: PMC2398769.
    40. Carroll JC, Pike CJ. Selective estrogen receptor modulators differentially regulate Alzheimer-like changes in female 3xTg-AD mice. Endocrinology. 2008 May; 149(5):2607-11. PMID: 18276750; PMCID: PMC2329277.
    41. Carroll JC, Rosario ER, Chang L, Stanczyk FZ, Oddo S, LaFerla FM, Pike CJ. Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J Neurosci. 2007 Nov 28; 27(48):13357-65. PMID: 18045930.
      View in: PubMed
    42. Pike CJ, Nguyen TV, Ramsden M, Yao M, Murphy MP, Rosario ER. Androgen cell signaling pathways involved in neuroprotective actions. Horm Behav. 2008 May; 53(5):693-705. PMID: 18222446; PMCID: PMC2424283.
    43. Rosario ER, Pike CJ. Androgen regulation of beta-amyloid protein and the risk of Alzheimer's disease. Brain Res Rev. 2008 Mar; 57(2):444-53. PMID: 17658612; PMCID: PMC2390933.
    44. Nguyen TV, Yao M, Pike CJ. Flutamide and cyproterone acetate exert agonist effects: induction of androgen receptor-dependent neuroprotection. Endocrinology. 2007 Jun; 148(6):2936-43. PMID: 17347309.
      View in: PubMed
    45. Yao M, Nguyen TV, Pike CJ. Estrogen regulates Bcl-w and Bim expression: role in protection against beta-amyloid peptide-induced neuronal death. J Neurosci. 2007 Feb 07; 27(6):1422-33. PMID: 17287517.
      View in: PubMed
    46. Rosario ER, Carroll JC, Oddo S, LaFerla FM, Pike CJ. Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. J Neurosci. 2006 Dec 20; 26(51):13384-9. PMID: 17182789.
      View in: PubMed
    47. Rosario ER, Ramsden M, Pike CJ. Progestins inhibit the neuroprotective effects of estrogen in rat hippocampus. Brain Res. 2006 Jul 12; 1099(1):206-10. PMID: 16793026.
      View in: PubMed
    48. Pike CJ, Rosario ER, Nguyen TV. Androgens, aging, and Alzheimer's disease. Endocrine. 2006 Apr; 29(2):233-41. PMID: 16785599.
      View in: PubMed
    49. Cordey M, Pike CJ. Conventional protein kinase C isoforms mediate neuroprotection induced by phorbol ester and estrogen. J Neurochem. 2006 Jan; 96(1):204-17. PMID: 16336227.
      View in: PubMed
    50. Nguyen TV, Yao M, Pike CJ. Androgens activate mitogen-activated protein kinase signaling: role in neuroprotection. J Neurochem. 2005 Sep; 94(6):1639-51. PMID: 16011741.
      View in: PubMed
    51. Cordey M, Gundimeda U, Gopalakrishna R, Pike CJ. The synthetic estrogen 4-estren-3 alpha,17 beta-diol (estren) induces estrogen-like neuroprotection. Neurobiol Dis. 2005 Jun-Jul; 19(1-2):331-9. PMID: 15837589.
      View in: PubMed
    52. Cordey M, Pike CJ. Neuroprotective properties of selective estrogen receptor agonists in cultured neurons. Brain Res. 2005 May 31; 1045(1-2):217-23. PMID: 15910780.
      View in: PubMed
    53. Yao M, Nguyen TV, Pike CJ. Beta-amyloid-induced neuronal apoptosis involves c-Jun N-terminal kinase-dependent downregulation of Bcl-w. J Neurosci. 2005 Feb 02; 25(5):1149-58. PMID: 15689551.
      View in: PubMed
    54. Rosario ER, Chang L, Stanczyk FZ, Pike CJ. Age-related testosterone depletion and the development of Alzheimer disease. JAMA. 2004 Sep 22; 292(12):1431-2. PMID: 15383512.
      View in: PubMed
    55. Ramsden M, Berchtold NC, Patrick Kesslak J, Cotman CW, Pike CJ. Exercise increases the vulnerability of rat hippocampal neurons to kainate lesion. Brain Res. 2003 May 09; 971(2):239-44. PMID: 12706240.
      View in: PubMed
    56. Cordey M, Gundimeda U, Gopalakrishna R, Pike CJ. Estrogen activates protein kinase C in neurons: role in neuroprotection. J Neurochem. 2003 Mar; 84(6):1340-8. PMID: 12614334.
      View in: PubMed
    57. Soreghan B, Pike C, Kayed R, Tian W, Milton S, Cotman C, Glabe CG. The influence of the carboxyl terminus of the Alzheimer Abeta peptide on its conformation, aggregation, and neurotoxic properties. Neuromolecular Med. 2002; 1(1):81-94. PMID: 12025818.
      View in: PubMed
    58. Pike CJ. Testosterone attenuates beta-amyloid toxicity in cultured hippocampal neurons. Brain Res. 2001 Nov 16; 919(1):160-5. PMID: 11689174.
      View in: PubMed
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