Endocrine

, Volume 29, Issue 2, pp 233–241

Androgens, aging, and Alzheimer's disease

  • Christian J. Pike
  • Emily R. Rosario
  • Thuy-Vi V. Nguyen
Article

Abstract

Testoterone depletion is a normal consequence of aging in men that is associated with senescent effects in androgen-responsive tissues. We discuss new evidence that one consequence of testosterone depletion in men is an increased risk for the development of Alzheimer's disease (AD). Furthermore, we discuss two candidate mechanisms by which test osterone may affect AD pathogenesis. First, testosterone has been identified as an endogenous regulator of β-amyloid, a protein that abnormally accumulates in AD brain and is implicated as a causal factor in the disease. Second, findings from several different paradigms indicate that testosterone has both neurotrophic and neuroprotective functions. These new findings support the clinical evaluation of androgen-based therapies for the prevention and treatment of AD.

Key words

Testosterone Alzheimer's disease β-amyloid neuroprotection dihydrotestosterone luteinizing hormone 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Paganini-Hill, A. and Henderson, V. W. (1994). Am. J. Epidemiol. 140, 256–261.PubMedGoogle Scholar
  2. 2.
    Henderson, V. W., Paganini-Hill, A., Emanuel, C. K., Dunn, M. E., and Buckwalter, J. G. (1994). Arch. Neurol. 51, 896–900.PubMedGoogle Scholar
  3. 3.
    Henderson V. W. (1997). Neurology 48, S27–35.PubMedGoogle Scholar
  4. 4.
    Cholerton, B., Gleason, C. E., Baker, L. D., and Asthana, S. (2002). Drugs Aging 19, 405–427.PubMedGoogle Scholar
  5. 5.
    Feldman, H. A., Longcope, C., Derby, C. A., et al. (2002). J. Clin. Endocrinol. Metab. 87, 589–598.PubMedGoogle Scholar
  6. 6.
    Gray, A., Feldman, H. A., McKinlay, J. B., and Longcope, C. (1991). J. Clin. Endocrinol. Metab. 73, 1016–1025.PubMedGoogle Scholar
  7. 7.
    Muller, M., den Tonkelaar, I., Thijssen, J. H., Grobbee, D. E., and van der Schouw, Y. T. (2003). Eur. J. Endocrinol. 149, 583–589.PubMedGoogle Scholar
  8. 8.
    Purifoy, F. E., Koopmans, L. H. and Mayes, D. M. (1981). Hum. Biol. 53, 499–511.PubMedGoogle Scholar
  9. 9.
    Vermeulen, A., Kaufman, J. M., and Giagulli, V. A. (1996). J. Clin. Endocrinol. Metab. 81, 1821–1826.PubMedGoogle Scholar
  10. 10.
    Harman, S. M., Metter, E. J., Tobin, J. D., Pearson, J., and Blackman, M. R. (2001). J. Clin. Endocrinol. Metab. 86, 724–731.PubMedGoogle Scholar
  11. 11.
    Nankin, H. R. and Calkins, J. H. (1986). J. Clin. Endocrinol. Metab. 63, 1418–1420.PubMedGoogle Scholar
  12. 12.
    Lewis, J. G., Ghanadian, R., and Chisholm, G. D. (1976). Acta Endocrinol. (Copenh.) 82, 444–448.Google Scholar
  13. 13.
    Pirke K. M. and Doerr, P. (1973). Acta Endocrinol. (Copenh.) 74, 792–800.Google Scholar
  14. 14.
    Pirke, K. M. and Doerr, P. (1975). Acta Endocrinol. (Copenh.) 79, 357–365.Google Scholar
  15. 15.
    Pirke, K. M. and Doerr, P. (1975). Acta Endocrinol. (Copenh.) 80, 171–178.Google Scholar
  16. 16.
    Stearns, E. L., MacDonnell, J. A., Kaufman, B. J., et al. (1974). Am. J. Med. 57, 761–766.PubMedGoogle Scholar
  17. 17.
    Vermeulen, A., Kaufman, J. M., and Giasulli, V. A. (1996). J. Clin Endocrinol. Metab. 81, 1821–1826.PubMedGoogle Scholar
  18. 18.
    Vermeulen, A., Rubens, R., and Verdonck, L. (1972). J. Clin. Endocrinol. Metab. 34, 730–735.PubMedGoogle Scholar
  19. 19.
    Baker, H. W., Burger, H. G., de Kretser, D. M., et al. (1976). Clin. Endocrinol. 5, 349–372.Google Scholar
  20. 20.
    Davidson, J. M., Chen, J. J., Crapo, L., Gray, G. D., Greenleaf, W. J., and Catania, J. A. (1983). J. Clin. Endocrinol. Metab. 57, 71–77.PubMedGoogle Scholar
  21. 21.
    Morley, J. E., Kaiser, F. E., Perry, H. M., et al. (1997). Metabolism 46, 410–413.PubMedGoogle Scholar
  22. 22.
    Zmuda, J. M., Cauley, J. A., Kriska, A., Glynn, N. W., Gutai, J. P., and Kuller, L. H. (1997). Am. J. Epidemiol. 146, 609–617.PubMedGoogle Scholar
  23. 23.
    Rosario, E. R., Chang, L., Stanczyk, F. Z., and Pike, C. J. (2004). JAMA 292, 1431–1432.PubMedGoogle Scholar
  24. 24.
    Swerdloff, R. S. and Wang, C., (2004). Best Pract. Res. Clin. Endocrinol. Metab. 18, 349–362.PubMedGoogle Scholar
  25. 25.
    Morley, J. E. (2001). Maturitas 38, 61–71; discussion 71-63.PubMedGoogle Scholar
  26. 26.
    Korenman, S. G., Morley, J. E., Mooradian, A. D. et al. (1990). J. Clin. Endocrinol. Metab. 71, 963–969.PubMedGoogle Scholar
  27. 27.
    Kaufman, J. M. and Vermeulen A. (2005). Endocr. Rev. 26, 833–876.PubMedGoogle Scholar
  28. 28.
    Baumgartner, R. N., Waters, D. L., Gallagher, D., Morley, J. E. and Garry, P. J. (1999). Mech. Ageing Dev. 107, 123–136.PubMedGoogle Scholar
  29. 29.
    Sheffield-Moore, M. and Urban, R. J. (2004). Trends Endocrinol. Metab. 15, 110–115.PubMedGoogle Scholar
  30. 30.
    Reed, R. L., Pearlmutter, L., Yochum, K., Meredith, K. E., and Mooradian, A. D. (1991). J. Am. Geriatr. Soc. 39, 555–561.PubMedGoogle Scholar
  31. 31.
    Frontera, W. R., Hughes, V. A., Fielding, R. A., Fiatarone, M. A., Evans, W. J., and Roubenoff, R. (2000). J. Appl. Physiol. 88, 1321–1326.PubMedGoogle Scholar
  32. 32.
    Bhasin, S., Woodhouse, L., and Storer, T. W. (2001). J. Endocrinol. 170, 27–38.PubMedGoogle Scholar
  33. 33.
    Burger, H., de Laet, C. E., van Daele, P. L., et al. (1998). Am. J. Epidemiol. 147, 871–879.PubMedGoogle Scholar
  34. 34.
    Jones, G., Nguyen, T., Sambrook, P., Kelly, P. J., and Eisman, J. A. (1994). BMJ 309, 691–695.PubMedGoogle Scholar
  35. 35.
    Orwoll, E. S. and Klein, R. F. (1995). Endocr. Rev. 16, 87–116.PubMedGoogle Scholar
  36. 36.
    Gooren, L. (2003). J. Steroid Biochem. Mol. Biol. 85, 349–355.PubMedGoogle Scholar
  37. 37.
    Bowen, R. L., Isley, J. P., and Atkinson, R. L. (2000). J. Neuroendocrinol. 12, 351–354.PubMedGoogle Scholar
  38. 38.
    Breuer, B., Trungold, S., Martucci, C., et al. (2001). Maturitas 39, 147–159.PubMedGoogle Scholar
  39. 39.
    Abbasi, A., Mattson, D. E., Cuisinier, M., et al. (1994). Arch. Phys. Med. Rehabil. 75, 594–599.PubMedGoogle Scholar
  40. 40.
    Thomas, J. L., Quang, B. T., Ochsenbein, E., and Vincent J. P. (2003). J. Nutr. Health Aging 7, 437–439.PubMedGoogle Scholar
  41. 41.
    Abbasi, A. A., Drinka, P. J., Mattson, D. E., and Rudman, D. (1993). J. Am. Geriatr. Soc. 41, 975–982.PubMedGoogle Scholar
  42. 42.
    Hogervorst, E., Williams, J., Budge, M., Barnetson, L., Combrinck, M., and Smith, A. D. (2001). Neuro. Endocrinol. Lett. 22, 163–168.PubMedGoogle Scholar
  43. 43.
    Hogervorst, E., Combrinck, M., and Smith, A. D. (2003). Neuro. Endocrinol. Lett. 24, 203–208.PubMedGoogle Scholar
  44. 44.
    Hogervorst, E., Lehmann, D. J., Warden, D. R., McBroom, J., and Smith, A. D. (2002). Int. J. Geriatr. Psychiatry 17, 938–940.PubMedGoogle Scholar
  45. 45.
    Lehmann, D. J., Hogervorst, E., Warden, D. R., Smith, A. D., Butler, H. T., and Ragoussis, J. (2004). J. Neurol. Neurosurg. Psychiatry 75, 163–164.PubMedGoogle Scholar
  46. 46.
    Hogervorst, E., Bandelow, S., Combrinck, M., and Smith, A. D. (2004). Exp. Gerontol. 39, 1633–1639.PubMedGoogle Scholar
  47. 47.
    Watanabe, T., Koba, S., Kawamura, M., et al. (2004). Metabolism 53, 476–482.PubMedGoogle Scholar
  48. 48.
    Paoletti, A. M., Congia, S., Lello, S. et al. (2004). Neurology, 62, 301–303.PubMedGoogle Scholar
  49. 49.
    Rasmuson, S., Nasman, B., Carlstrom, K., and Olsson, T. (2002). Dement. Geriatr. Cogn. Disord. 13, 74–79.PubMedGoogle Scholar
  50. 50.
    Almeida, O. P., Riono, A., Clarnette, R., and Martins, R. N. (2000). Alzheimer's Rep. 3, 15–18.Google Scholar
  51. 51.
    Pennanen, C., Laakso, M. P., Kivipelto, M., Ramberg, J., and Soininen, H. (2004). J. Neuroendocrinol. 16, 95–98.PubMedGoogle Scholar
  52. 52.
    Militello, A., Vitello, G., Lunetta, C., et al. (2002). J. Neurol. Sci. 195, 67–70.PubMedGoogle Scholar
  53. 53.
    Markianos, M., Panas, M., Kalfakis, N., and Vassilopoulos, D. (2005). Ann. Neurol. 57, 520–525.PubMedGoogle Scholar
  54. 54.
    Okun, M. S., DeLong, M. R., Hanfelt, J., Gearing, M., and Levey, A. (2004). Neurology 62, 411–413.PubMedGoogle Scholar
  55. 55.
    Cunningham, C. J., Sinnott, M., Denihan, A., et al. (2001). J. Clin. Endocrinol. Metab. 86, 1099–1103.PubMedGoogle Scholar
  56. 56.
    Hoskin, E. K., Tang, M. X., Manly, J. J., and Mayeux, R. (2004). Neurobiol. Aging. 25, 141–147.PubMedGoogle Scholar
  57. 57.
    Spratt, D. I., Cox, P., Orav, J., Moloney, J. and Bigos, T. (1993). J. Clin. Endocrinol. Metab. 76, 1548–1554.PubMedGoogle Scholar
  58. 58.
    Wang, C., Chan, V., and Yeung, R. T. (1978). Clin. Endocrinol. (Oxf.) 9, 255–266.Google Scholar
  59. 59.
    Woolf, P. D., Hamill, R. W., McDonald, J. V., Lee, L. A., and Kelly, M. (1985). J. Clin. Endocrinol. Metab. 60, 444–450.PubMedGoogle Scholar
  60. 60.
    Barrett-Connor, E., Khaw, K. T. and Yen, S. S. (1990). Am. J. Epidemiol. 132, 895–901.PubMedGoogle Scholar
  61. 61.
    Andersson, B., Marin, P., Lissner, L., Vermeulen, A., and Bjorntorp, P. (1994). Diabetes Care 17, 405–411.PubMedGoogle Scholar
  62. 62.
    Contoreggi, C. S., Blackman, M. R., Andres, R. et al. (1990). J. Androl. 11, 460–470.PubMedGoogle Scholar
  63. 63.
    McDonald, J. A., Handelsman, D. J., Dilworth, J., Conway, A. J., and McCaughan, G. W. (1993). J. Gastroenterol. Hepatol. 8, 247–253.PubMedGoogle Scholar
  64. 64.
    Handelsman, D. J. and Dong, Q. (1993). Endocrinol. Metab. Clin. North Am. 22, 145–161.PubMedGoogle Scholar
  65. 65.
    Bannister, P., Oakes, J., Sheridan, P., and Losowsky, M. S. (1987). Q. J. Med. 63, 305–313.PubMedGoogle Scholar
  66. 66.
    Elewaut, A., Barbier, F., and Vermeulen, A. (1979). Z. Gastroenterol. 17, 402–405.PubMedGoogle Scholar
  67. 67.
    Moffat, S. D., Zonderman, A. B., Metter, E. J., et al. (2004). Neurology 62, 188–193.PubMedGoogle Scholar
  68. 68.
    Deslypere, J. P. and Vermeulen, A. (1981). J. Clin. Endocrinol. Metab. 53, 430–434.PubMedGoogle Scholar
  69. 69.
    Pardridge, W. M. (1981). Endocr. Rev. 2, 103–123.PubMedGoogle Scholar
  70. 70.
    Twist, S. J., Taylor, G. A., Weddell, A., Weightman, D. R., Edwardson, J. A., and Morris, C. M. (2000). Neurosci. Lett. 286, 1–4.PubMedGoogle Scholar
  71. 71.
    Brinton, R. D. (2004). CNS Drugs 18, 405–422.PubMedGoogle Scholar
  72. 72.
    Raber, J. (2004). Sci. Aging Knowledge Environ. 2004, re2.PubMedGoogle Scholar
  73. 73.
    Strittmatter, W. J. and Roses, A. D. (1996). Annu. Rev. Neurosci. 19, 53–77.PubMedGoogle Scholar
  74. 74.
    Raber, J., Huang, Y., and Ashford, J. W. (2004). Neurobiol. Aging 25, 641–650.PubMedGoogle Scholar
  75. 75.
    Roses, A. D., Saunders, A. M., Corder, E. H., et al. (1995). Arzneimittelforschung 45, 413–417.PubMedGoogle Scholar
  76. 76.
    Raber, J., Bongers, G., LeFevour, A., Buttini, M., and Mucke, L. (2002). J. Neurosci. 22, 5204–5209.PubMedGoogle Scholar
  77. 77.
    Colton, C. A., Brown, C. M., and Vitek, M. P. (2005). Neurobiol. Aging 26, 363–372.PubMedGoogle Scholar
  78. 78.
    Hardy, J., (1997). Trends Neurosci. 20, 154–159.PubMedGoogle Scholar
  79. 79.
    Hardy, J. A. and Higgins, G. A. (1992). Science 256, 184–185.PubMedGoogle Scholar
  80. 80.
    Vincent, B. and Smith, J. D. (2000). Biochem. Biophys. Res. Commun. 271, 82–85.PubMedGoogle Scholar
  81. 81.
    Manthey, D., Heck, S., Engert, S., and Behl, C. (2001). Eur. J. Biochem. 268, 4285–4291.PubMedGoogle Scholar
  82. 82.
    Jaffe, A. B., Toran-Allerand, C. D., Greengard, P., and Grandy, S. E. (1994). J. Biol. Chem. 269, 13065–13068.PubMedGoogle Scholar
  83. 83.
    Greenfield, J. P., Leung, L. W., Cai, D., et al. (2002). J. Biol. Chem. 277, 12128–12136.PubMedGoogle Scholar
  84. 84.
    Savage, M. J., Trusko, S. P., Howland, D. S., et al. (1998). J. Neurosci. 18, 1743–1752.PubMedGoogle Scholar
  85. 85.
    Xu, H., Gouras, G. K., Greenfield, J. P., et al. (1998). Nat. Med. 4, 447–451.PubMedGoogle Scholar
  86. 86.
    Petanceska, S. S., Nagy, V., Frail, D., and Gandy, S. (2000). Neurology 54, 2212–2217.PubMedGoogle Scholar
  87. 87.
    Zheng, H., Xu, H., Uljon, S. N., et al. (2002). J. Neurochem. 80, 191–196.PubMedGoogle Scholar
  88. 88.
    Levin-Allerhand, J. A., Lominska, C. E., Wang, J., and Smith, J. D. (2002). J. Alzheimers Dis. 4, 449–457.PubMedGoogle Scholar
  89. 89.
    Schonknecht, P., Pantel, J., Klinga, K., et al. (2001). Neurosci. Lett. 307, 122–124.PubMedGoogle Scholar
  90. 90.
    Baker, L. D., Sambamurti, K., Craft, S. et al. (2003). Am. J. Geriatr. Psychiatry 11, 239–244.PubMedGoogle Scholar
  91. 91.
    Gouras, G. K., Xu, H., Gross, R. S., et al., (2000). Proc. Nattl. Acad. Sci. USA 97, 1202–1205.PubMedGoogle Scholar
  92. 92.
    Selkoe, D. J. (1989). Ann. Med. 21, 73–76.PubMedGoogle Scholar
  93. 93.
    Poletti, A., Negri-Cesi, P., Melcangi, R. C., Colciago, A., Martini, L., and Celotti, F. (1997). J. Neurochem. 68, 1298–1303.PubMedGoogle Scholar
  94. 94.
    Melcangi, R. C., Celotti F., Castano, P., and Martini, L. (1992) Brain Res. 585, 411–415.PubMedGoogle Scholar
  95. 95.
    Goodenough, S., Engert, S., and Behl, C. (2000). Neurosci. Lett., 296, 49–52.PubMedGoogle Scholar
  96. 96.
    Ramsden, M., Nyborg, A. C., Murphy, M. P., et al. (2003). J. Neurochem. 87, 1052–1055.PubMedGoogle Scholar
  97. 97.
    Gandy, S., Almeida, O. P., Fonte, J., et al. (2001). JAMA 285, 2195–2196.PubMedGoogle Scholar
  98. 98.
    Almeida, O. P., Waterreus, A., Spry, N., Flicker, L., and Martins, R. N. (2004). Psychoneuroendocrinology, 29, 1071–1081.PubMedGoogle Scholar
  99. 99.
    Gillett, M. J., Martins, R. N., Clarnette, R. M., Chubb, S. A., Bruce, D. G., and Yeap, B. B. (2003). J. Alzheimers Dis. 5, 267–269.PubMedGoogle Scholar
  100. 100.
    Nordeen, E. J., Nordeen, K. W., Sengelaub, D. R., and Arnold, A. P. (1985). Science 229, 671–673.PubMedGoogle Scholar
  101. 101.
    Nuñez, J. L., Sodhi, J., and Juraska, J. M. (2002). J. Neurobiol. 52, 312–321.PubMedGoogle Scholar
  102. 102.
    Lund, T. D., Salyer, D. L., Fleming, D. E., and Lephart, E. D. (2000). Dev. Brain Res. 120, 261–266.Google Scholar
  103. 103.
    Sengelaub, D. R., Nordeen, E. J., Nordeen K. W., and Arnold, A. P. (1989). J. Comp. Neurol., 280, 637–644.PubMedGoogle Scholar
  104. 104.
    Beyer, C., Green, S. J., and Hutchison, J. B. (1994). Endocrinology 135, 1220–1226.PubMedGoogle Scholar
  105. 105.
    Zhang, L., Chang, Y. H., Barker, J. L., et al. (2000). Neurosci. Lett., 281, 57–60.PubMedGoogle Scholar
  106. 106.
    Beyer, C. and Hutchison, J. B. (1997). Dev. Brain Res. 98, 74–81.Google Scholar
  107. 107.
    Marron, T. U., Guerini, V., Rusmini, P., et al. (2005). J. Neurochem. 92, 10–20.PubMedGoogle Scholar
  108. 108.
    Lustig, R. H., Hua, P., Smith, L. S., Wang, C., and Chang, C. (1994). Mol. Cell Neurosci. 5, 587–596.PubMedGoogle Scholar
  109. 109.
    Hauser, K. F., MacLusky, N. J. and Toran-Allerand, C. D. (1987). Brain Res. 406, 62–72.PubMedGoogle Scholar
  110. 110.
    Leranth, C., Petnehazy, O., and MacLusky, N. J. (2003). J. Neurosci. 23, 1588–1592.PubMedGoogle Scholar
  111. 111.
    Leranth, C., Hajszan, T., and MacLusky, N. J. (2004). J. Neurosci. 24, 495–499.PubMedGoogle Scholar
  112. 112.
    Pouliot, W. A., Handa, R. J. and Beck, S. G. (1996). Synapse 23, 10–19.PubMedGoogle Scholar
  113. 113.
    Smith, M. D., Jones, L. S., and Wilson, M. A. (2002). Neuroscience 109, 517–530.PubMedGoogle Scholar
  114. 114.
    Kurz, E. M., Sengelaub, D. R., and Arnold, A. P. (1986). Science 232, 395–398.PubMedGoogle Scholar
  115. 115.
    Brooks, B. P., Merry, D. E., Paulson, H. L., Lieberman, A. P., Kolson, D. L., and Fischbeck, K. H. (1998). J. Neurochem. 70, 1054–1060.PubMedGoogle Scholar
  116. 116.
    Matsumoto, A. (1997). Brain Res. Bull. 444 539–547.Google Scholar
  117. 117.
    Matsumoto, A. (2001). J. Comp. Neurol. 430, 389–395.PubMedGoogle Scholar
  118. 118.
    Keast, J. R. and Saunders, R. J. (1998). Neuroscience, 85, 543–556.PubMedGoogle Scholar
  119. 119.
    Meusburger, S. M. and Keast, J. R. (2001). Neuroscience, 108, 331–340.PubMedGoogle Scholar
  120. 120.
    Day, J. R., Laping, N. J., Lampert-Etchells, M. et al. (1993). Neuroscience 55, 435–443.PubMedGoogle Scholar
  121. 121.
    Nichols, N. R., Day, J. R., Laping, N. J., Johnson, S. A., and Finch, C. E. (1993). Neurobiol. Aging 14, 421–429.PubMedGoogle Scholar
  122. 122.
    Laping, N. J., Teter, B., Anderson, C. P., et al. (1994). J. Neurosci. Res. 39, 710–717.PubMedGoogle Scholar
  123. 123.
    Garcia-Segura, L. M., Duenas, M., Busiguina, S., Naftolin, F., and Chowen, J. A. (1995). J. Steroid Biochem. Mol. Biol. 53, 293–298.PubMedGoogle Scholar
  124. 124.
    Garcia-Estrada, J., Del Rio, J. A., Luquin, S., Soriano, E., and Garcia-Segura, L. M. (1993). Brain Res. 628, 271–278.PubMedGoogle Scholar
  125. 125.
    Mong, J. A., Glaser, E., and McCarthy, M. M. (1999). J. Neurosci. 19, 1464–1472.PubMedGoogle Scholar
  126. 126.
    Jones, K. J., Brown, T. J., and Damaser, M. (2001). Brain Res. Brain Res. Rev. 37, 372–382.PubMedGoogle Scholar
  127. 127.
    Yu, W. H. and Srinivasan, R. (1981). Exp. Neurol. 71, 431–435.PubMedGoogle Scholar
  128. 128.
    Yu, W. H. (1982). Exp. Neurol. 77, 129–141.PubMedGoogle Scholar
  129. 129.
    Kujawa, K. A., Tanzer, L. and Jones, K. J. (1995). Exp. Neurol. 133, 138–143.PubMedGoogle Scholar
  130. 130.
    Kujawa, K. A., Emeric, E., and Jones, K. J. (1991). J. Neurosci. 11, 3898–3906.PubMedGoogle Scholar
  131. 131.
    Tanzer, L. and Jones, K. J. (1997). Exp. Neurol. 146, 258–264.PubMedGoogle Scholar
  132. 132.
    Yu, W. H. (1988). Exp. Neurol. 102, 230–235.PubMedGoogle Scholar
  133. 133.
    Yu, W. H. (1989). J. Neurosci. 9, 3908–3914.PubMedGoogle Scholar
  134. 134.
    Huppenbauer, C. B., Tanzer, L., DonCarlos, L. L., and Jones, K. J. (2005). J. Neurosci. 25, 4004–4013.PubMedGoogle Scholar
  135. 135.
    Yu, W. H., and Cao, C. G. (1991). Neuroreport 2, 258–260.PubMedGoogle Scholar
  136. 136.
    Simerly, R. B., Chang, C., Muramatsu, M., and Swanson, L. W. (1990). J. Comp. Neurol., 294, 76–95.PubMedGoogle Scholar
  137. 137.
    Kerr, J. E., Allore, R. J., Beck, S. G., and Handa, R. J. (1995). Endocrinology 136, 3213–3221.PubMedGoogle Scholar
  138. 138.
    Van Hoesen G. W. and Hyman B. T. (1990). Prog. Brain. Res. 83, 445–457.PubMedGoogle Scholar
  139. 139.
    Hyman, B. T., Van Hoesen, G. W., Damasio, A. R., and Barnes, C. L. (1984). Science 225, 1168–1170.PubMedGoogle Scholar
  140. 140.
    Kamsden, M., Shin, T. M., and Pike, C. J. (2003). Neuroscience 122, 573–578.Google Scholar
  141. 141.
    Azcoitia, I., Sierra, A., Veiga, S., Honda, S., Harada N. and Garcia-Segura, L. M. (2001). J. Neurobiol. 47, 318–329.PubMedGoogle Scholar
  142. 142.
    Rhodes, M. E. and Frye, C. A. (2004). Pharmacol. Biochem. Behav. 78, 483–493.PubMedGoogle Scholar
  143. 143.
    Rhodes, M. E., Harney, J. P., and Frye, C. A. (2004). Brain Res., 1000, 8–18.PubMedGoogle Scholar
  144. 144.
    Frye, C. A. (2001). Brain Res. Brain Res. Rev. 37, 201–222.PubMedGoogle Scholar
  145. 145.
    Frye, C. A. and Reed, T. A. (1998). Psychoneuroendocrinology 23, 385–399.PubMedGoogle Scholar
  146. 146.
    Dluzen, D. E., McDermott, J. L., and Liu, B. (1996). J. Neurochem. 66, 658–666.PubMedGoogle Scholar
  147. 147.
    Dluzen, D. E. (1996). Brain Res. 715, 113–118.PubMedGoogle Scholar
  148. 148.
    Gao, X. and Dluzen, D. E. (1001). Brain Res. 892, 63–69.Google Scholar
  149. 149.
    Ekue, A., Boulanger, J. F., Morissette, M., and Di Paolo, T. (2002). J. Neuroendocrinol., 14, 731–736.PubMedGoogle Scholar
  150. 150.
    Nishino, H., Nakajima, K., Kumazaki, M., et al. (1998). Neurosci. Res. 30, 303–312.PubMedGoogle Scholar
  151. 151.
    Yang, S. H., Perez, E., Cutright, J., et al. (2002). J. Appl. Physiol. 92, 195–201.PubMedGoogle Scholar
  152. 152.
    Hawk, T., Zhang, Y. O., Rajakumar, G., Day, A. L., and Simpkins, J. W. (1998). Brain Res. 796, 296–298.PubMedGoogle Scholar
  153. 153.
    Hammond, J., Le, Q., Goodyer, C., Gelfand, M., Trifiro, M., and LeBlanc, A. (2001). J. Neurochem. 77, 1319–1326.PubMedGoogle Scholar
  154. 154.
    Ahlbom, E., Prins, G. S., and Ceccatelli, S. (2001). Brain Res. 892, 255–262.PubMedGoogle Scholar
  155. 155.
    Pike, C. J. (2001). Brain Res. 919, 160–165.PubMedGoogle Scholar
  156. 156.
    Zhang, Y., Champagne, N., Beitel, L. K., Goodyer, C. G., Trifiro, M., and LeBlanc, A. (2004). J. Neurosci., 24, 5315–5321.PubMedGoogle Scholar
  157. 157.
    Papasozomenos, S. C. H. and Shanavas, A. (2002). Proc. Natl. Acad. Sci. USA 99, 1140–1145.PubMedGoogle Scholar
  158. 158.
    Nguyen, T. V., Yao, M., and Pike, C. J. (2005). J. Neurochem. 94, 1639–1651.PubMedGoogle Scholar
  159. 159.
    Kelly, S. and Yenari, M. A. (2002). Curr. Med. Res. Opin, 18(Suppl. 2), s55-s60.PubMedGoogle Scholar
  160. 160.
    Gregory, C. W. and Bowen, R. L. (2005). Cell. Mol. Life Sci. 62, 313–319.PubMedGoogle Scholar
  161. 161.
    Short, R. A., Bowen, R. L., O'Brien, P. C., and Graff-Radford, N. R. (2001). Mayo Clin. Proc. 76, 906–909.PubMedGoogle Scholar
  162. 162.
    Drouin, J. and Labrie, F. (1976). Endocrinology 98, 1528–1534.PubMedGoogle Scholar
  163. 163.
    Gill, M. K., Karanth, S., Dutt, A., and Juneja, H. S. (1985). Horn. Metab. Res. 17, 141–146.Google Scholar
  164. 164.
    Lindzey, J., Wetsel, W. C., Gouse, J. F., Stoker, T., Cooper, R., and Korach, K. S. (1998). Endocrinology 139, 4092–4101.PubMedGoogle Scholar
  165. 165.
    Bowen, R. L., Verdile, G., Liu, T., et al. (2004). J. Biol. Chem. 279, 20539–20545.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Christian J. Pike
    • 1
  • Emily R. Rosario
    • 1
  • Thuy-Vi V. Nguyen
    • 1
  1. 1.Anurs Gerontology CenterUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations