Androgens exert direct neuroprotective effects on the brain: A review of pre-clinical evidences

Journal of Andrological Sciences

Volumn 17, Issue 2, 2010, Pages 49-55

  Creta, M ^a   Riccio, R ^a   Chiancone, F ^a   Fusco, F ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

Androgens; Brain; Neuroprotection

Indexed keywords

EID: 78650268521     PISSN: 20353901     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (44)

1. Pike CJ, Nguyen TV, Ramsden M, et al. Androgen cell signaling pathways involved in neuroprotective actions. Horm Behav 2008;53:693-705.
2. Garcia-Segura LM, Balthazart J. Steroids and neuroprotection: new advances. Front Neuroendocrinol 2009;30:v-ix.
3. Martini L, Melcangi RC, Maggi R. Androgen and progesterone metabolism in the central and peripheral nervous system. J Steroid Biochem Mol Biol 1993;47:195-205.
4. Gatson JW, Kaur P, Singh M. Dihydrotestosterone differentially modulates the mitogen-activated protein kinase and the phosphoinositide 3-kinase/Akt pathways through the nuclear and novel membrane androgen receptor in C6 cells. Endocrinology 2006;147:2028-34.
5. Yao M, Nguyen TV, Rosario ER, et al. Androgens regulate neprilysin expression: role in reducing betaamyloid levels. J Neurochem 2008;105:2477-88.
6. Patchev VK, Schroeder J, Goetz F, et al. Neurotropic action of androgens: principles, mechanisms and novel targets. Exp Gerontol 2004;39:1651-60.
7. Gatson JW, Kaur P, Singh M. Dihydrotestosterone differentially modulates the mitogen-activated protein kinase and the phosphoinositide 3-kinase/Akt pathways through the nuclear and novel membrane androgen receptor in C6 cells. Endocrinology 2006;147:2028-34.
8. Hines M. Early androgen influences on human neural and behavioural development. Early Hum Dev 2008;84:805-7.
9. Moffat SD, Zonderman AB, Metter EJ, et al. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab 2002;87:5001-7.
10. Rosario ER, Chang L, Stanczyk FZ, et al. Age-related testosterone depletion and the development of Alzheimer disease. JAMA 2004;292:1431-2.
11. Goldman-Rakic P, Friedman H. The circuitry of working memory revealed by anatomy and metabolic imaging. In: Levin H, Eisenberg H, Benton A, editors. Frontal lobe function and dysfunction. New York: Oxford University Press 1991, pp. 72-91.
12. Hof PR, Morrison JH. The aging brain: morphomolecular senescence of cortical circuits. Trends Neurosci 2004;27:607-13.
13. Salat DH, Kaye JA, Janowsky JS. Selective preservation and degeneration within the prefrontal cortex in aging and Alzheimer disease. Arch Neurol 2001;58:1403-8.
14. Barrett-Connor E, Goodman-Gruen D, Patay B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 1999;84:3681-5.
15. Moffat SD, Zonderman AB, Metter EJ, et al. Free testosterone and risk for Alzheimer disease in older men. Neurology 2004;62:188-93.
16. Tan RS, Pu SJ. A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease. Aging Male 2003;6:13-7.
17. Salminen EK, Portin RI, Koskinen A, et al. Associations between serum testosterone fall and cognitive function in prostate cancer patients. Clin Cancer Res 2004;10:7575-82.
18. Almeida TA, Papadopoulos N. Progression model of prostate cancer. Methods Mol Biol 2003;222:211-22.
19. Ramsden M, Nyborg AC, Murphy MP, et al. Androgens modulate beta-amyloid levels in male rat brain. J Neurochem 2003;87:1052-5.
20. Almeida OP, Waterreus A, Spry N, et al. One year follow-up study of the association between chemical castration, sex hormones, beta-amyloid, memory and depression in men. Psychoneuroendocrinology 2004;29:1071-81.
21. Jeppesen LL, Jørgensen HS, Nakayama H, et al. Decreased serum testosterone in men with acute ischemic stroke. Arterioscler Thromb Vasc Biol 1996;16:749-54.
22. Repici M, Mariani J, Borsello T. Neuronal death and neuroprotection: a review. Methods Mol Biol 2007;399:1-14.
23. Turner PR, O'Connor K, Tate WP, et al. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 2003;70:1-32.
24. Selkoe DJ, Yamazaki T, Citron M, et al. The role of APP processing and trafficking pathways in the formation of amyloid beta-protein. Ann N Y Acad Sci 1996;777:57-64.
25. Pike CJ, Carroll JC, Rosario ER, et al. Protective actions of sex steroid hormones in Alzheimer's disease. Front Neuroendocrinol 2009;30:239-58.
26. Rosario ER, Carroll JC, Oddo S, et al. Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. J Neurosci 2006;26:13384-9.
27. McAllister C, Long J, Bowers A, et al. Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment. J Neurosci 2010;30:7326-34.
28. Zhang Y, Champagne N, Beitel LK, et al. Estrogen and androgen protection of human neurons against intracellular amyloid beta1-42 toxicity through heat shock protein 70. J Neurosci 2004;24:5315-21.
29. Iqbal K, Alonso Adel C, Chen S, et al. Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 2005;1739:198-210.
30. Papasozomenos SCh, Shanavas A. Testosterone prevents the heat shock-induced overactivation of glycogen synthase kinase-3 beta but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase and concomitantly abolishes hyperphosphorylation of tau: implications for Alzheimer's disease. Proc Natl Acad Sci USA 2002;99:1140-5.
31. Park SY, Tournell C, Sinjoanu RC, et al. Caspase-3- and calpain-mediated tau cleavage are differentially prevented by estrogen and testosterone in betaamyloid-treated hippocampal neurons. Neuroscience 2007;144:119-27.
32. Ramsden M, Shin TM, Pike CJ. Androgens modulate neuronal vulnerability to kainate lesion. Neuroscience 2003;122:573-8.
33. Hammond J, Le Q, Goodyer C, et al. Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons. J Neurochem 2001;77:1319-26.
34. Li ZK, Feng JX, Zhao CY, et al. Protection of androgen against hypoxic-ischemic brain damage in neonatal rats and possible mechanisms. Zhongguo Dang Dai Er Ke Za Zhi 2006;8:441-6.
35. Nguyen TV, Yao M, Pike CJ. Androgens activate mitogen-activated protein kinase signaling: role in neuroprotection. J Neurochem 2005;94:1639-51.
36. Gatson JW, Singh M. Activation of a membrane-associated androgen receptor promotes cell death in primary cortical astrocytes. Endocrinology 2007;148:2458-64.
37. Ahlbom E, Prins GS, Ceccatelli S. Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism. Brain Res 2001;892:255-62.
38. Day JR, Frank AT, O'Callaghan JP, et al. The effect of age and testosterone on the expression of glial fibrillary acidic protein in the rat cerebellum. Exp Neurol 1998;151:343-6.
39. Pekny M, Nilsson M. Astrocyte activation and reactive gliosis. Glia 2005;50:427-34.
40. Barreto G, Veiga S, Azcoitia I, et al. Testosterone decreases reactive astroglia and reactive microglia after brain injury in male rats: role of its metabolites, oestradiol and dihydrotestosterone. Eur J Neurosci 2001;25:3039-46.
41. Pan Y, Zhang H, Acharya AB, et al. Effect of testosterone on functional recovery in a castrate male rat stroke model. Brain Res 2005;1043:195-204.
42. Gu F, Hata R, Toku K, et al. Testosterone up-regulates aquaporin-4 expression in cultured astrocytes. J Neurosci Res 2003;72:709-15.
43. Frye CA, McCormick CM. Androgens are neuroprotective in the dentate gyrus of adrenalectomized female rats. Stress 2000;3:185-94.
44. Rhodes ME, Harney JP, Frye CA. Gonadal, adrenal, and neuroactive steroids' role in ictal activity. Brain Res 2004;1000:8-18.