ROLE OF THE HYPOTHALAMIC-PITUITARY-GONADAL SYSTEM IN THE PATHOGENESIS OF ALZHEIMER’S DISEASE

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Abstract


Alzheimer's disease (AD) is the most common from degenerative diseases of cerebrum which lead to the development of dementia. Because the exact causes of contraction of Alzheimer's disease (AD) are unknown, there is no adequate etiotropic therapy for this serious disease. Modern drugs present on the market, including cholinesterase inhibitors and NMDA antagonists, only alleviate symptoms without affecting the progression of AD. The review presents the results of modern studies confirming the significant contribution of gonadotropinreleasing hormone, gonadotropins and sex steroids to the development of mental aging. It is emphasized that the study of the role of the hypothalamic-pituitary-gonadal system in the etiopathogenesis of AD is certainly a promising area of psychoneuroendocrinology, which, perhaps, will lead to the development of new approaches to the treatment of this neurodegenerative disease. The contradictoriness of the data of a number of studies is noted and discussed.

O O Masalova

FSBSI “Institute of Experimental Medicine”

S B Kazakova

FSBI “The Research Institute of Influenza” of the Ministry of Health of the Russian Federation

N S Sapronov

FSBSI “Institute of Experimental Medicine”

Corresponding member of the Russian Academy of Sciences

  • Сапронов Н.С. Гонадолиберины. СПб.: Арт-Экспресс, 2012. 269 с. [Sapronov N.S. Gonadotropin-releasing hormone. St. Petersburg: Art-Express, 2012. 269 p.].
  • Rao C.V. Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women // Reprod. Sci. 2017. Vol. 24, No 3. Р. 355 -368.
  • Casadesus G., Webber K.M., Atwood C.S., Pappolla M.A., Perry G., Bowen R.L., Smith M.A. Luteinizing hormone modulates cognition and amyloid-beta deposition in Alzheimer APP transgenic mice // Biochim. Biophys. Acta. 2006. Vol. 1762, No 4. Р. 447-452.
  • Taxel P., Stevens M.C., Trahiotis M, Zimmerman J, Kaplan R.F. The effect of short-term estradiol therapy on cognitive function in older men receiving hormonal suppression therapy for prostate cancer // J. Am Geriatr. Soc. 2004. Vol. 52, No 2. Р. 269-273.
  • Гончаров Н.П. Антиандрогены и их применение при раке предстательной железы // Андрология и генитальная хирургия. 2002. No 2. С. 4 0$49. [Goncharov N.P. Antiandrogens and their use in prostate cancer, Andrology and genital surgery. 2002. No 2. pр. 40-49.]
  • Сапронов Н.С. Андрогены и ментальные расстройства. СПб.: Арт-Экспресс, 2017. 208 с. [Sapronov N.S. Androgens and mental disorders. St. Petersburg: Art-Express, 2017. 208 p.].
  • Сапронов Н.С., Байрамов A.A. Холинергические механизмы регуляции мужской половой функции. СПб.: Арт-Экспресс, 2013. 272 с. [Sapronov N.S., Bayramov A.A. Cholinergic mechanisms of regulation of male sexual function. St. Petersburg: Art-Express, 2013. 272 p.].
  • Ponholzer A, Madersbacher S, Rauchenwald M, Jungwirth S, Fischer P, Tragl K.H. Serum an drogen levels and their association to depression and Alzheimer dementia in a cohort of 75-year-old men over 5 years: results of the VITA study // Int. J. Impot. Res. 2009. Vol. 21, No 3. Р. 187-191.
  • Martin D.M., Wittert G, Burns N.R., Haren M.T., Sugarman R. Testosterone and cognitive function in ageing men: data from the Florey Adelaide Male Ageing Study (FAMAS) // Maturitas. 2007. Vol. 57, No 2. Р. 182-194.
  • Rodrigues M.A., Verdile G, Foster J.K., Hogervorst E, Joesbury K, Dhaliwal S, Corder E.H., Laws S.M., Hone E, Prince R, Devine A, Mehta P, Beilby J., Atwood C.S., Martins R.N. Gonadotropins and cognition in older women // J. Alzheimers Dis. 2008. Vol. 13, No 3. Р. 267-274.
  • Сапронов Н.С., Федотова Ю.О. Гормоны гипоталамо-гипофизарно-овариальной системы и мозг. СПб.: Формиздат, 2009. 592 с. [Sapronov N.S., Fedotova Yu.O. Hormones of the hypothalamic-pituitary-ovarian system and the brain. St. Petersburg: Formizdat, 2009. 592 p.].
  • Short R.A., Bowen R.L., O'Brien P.C., Graff-Radford Mayo N.R. Elevated gonadotropin levels in patients with Alzheimer disease // Clin. Proc. 2001. Vol. 76, No 9. Р. 906-909.
  • Bowen R.L., Smith M.A., Harris P.L., Kubat Z, Martins R.N., Castellani R.J., Perry G., Atwood C.S., Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology //J. Neurosci. Res. 2002. Vol. 70, No 3. Р. 514-518.
  • Drummond E.S., Martins R.N., Handelsman D.J., Harvey A.R. Altered expression of Alzheimer's disease-related proteins in male hypogonadal mice // Endocrinology. 2 012. Vol. 153, No 6. Р 2789-2799.
  • Zhang G, Li J., Purkayastha S, Tang Y, Zhang H. Hypothalamic programming of systemic ageing involving IKK-13, NF-kB and GnRH // Nature. 2013. Vol. 497, No 497. Р. 211-216.
  • Chu C., Gao G., Huang W. A study on co-localization of FSH and its receptor in rat hippocampus // J. Mol. Histol. 2008. Vol. 39, No 1. Р. 49-55.
  • Wilson A.C., Salamat M.S., Haasl R.J., Roche K.M., Karande A., Meethal S.V., Terasawa E, Bowen R.L., Atwood C.S. Human neurons express type I GnRH receptor and respond to GnRH I by increasing luteinizing hormone expression // J. Endocrinol. 2006. Vol. 191, No 3. Р. 651-663.
  • Anukulthanakorn K, Malaivijitnond S, Kitahashi T., Jaroenporn S, Parhar I. Molecular events during the induction of neurodegeneration and memory loss in estrogen-deficient rats // G en. Comp. Endocrinol. 2013. Vol. 181. Р. 316-323.
  • Saberi S, Du Y.P., Christie M, Goldsbury C. Human chorionic gonadotropin increases ЮВ-cleavage of amyloid precursor protein in SH-SY5Y cells // Cell Mol. Neurobiol. 2013. Vol. 33, No 6. Р. 747-751.
  • Verdile G, Yeap B.B., Clarnette R.M., Dhaliwal S, Burkhardt M.S., Chubb S.A., De Ruyck K, Rodrigues M, Mehta P.D., Foster J.K., Bruce D.G., Martins R.N. Luteinizing hormone levels are positively correlated w ith plasma amyloid-beta protein levels in elderly men // J. Alzheimers Dis. 2008. Vol. 14, No 2. Р. 201-208.
  • Lin J., Li X., Yuan F, Lin L., Cook C.L., Rao Ch. V, Lei Z. Genetic ablation of luteinizing hormone receptor improves the amyloid pathology in a mouse model of Alzheimer disease // J. Neuropathol. Exp. Neurol. 2010. Vol. 69, No 3. Р. 253-261.
  • Bukovsky A, Indrapichate K, Fujiwara H., Cekanova M, Ayala M.E., Dominguez R, Caudle M.R., Wimalsena J., Elder R.F., Copas P, Foster J.S., Fernando R.I., Henley D.C., Upadhyaya N.B. Multiple luteinizing hormone receptor (LHR) protein variants, interspecies reactivity of anti-LHR mAb clone 3B5, subcellular localization of LHR in human placenta, pelvic floor and brain, and possible role for LHR in the development of abnormal pregnancy, pelvic floor disorders and Alzheimer's disease // Reprod. Biol. Endocrinol. 2003. No 1. Р. 46.
  • Butchart J., Birch B, Bassily R, Wolfe L, Holmes C. Male sex hormones and systemic inflammation in Alzheimer disease // Alzheimer Dis. Assoc. Disord. 2013. Vol. 27, No 2. Р. 153-156.
  • Atwood C.S., Bowen R.L. Molecular events during the induction of neurodegeneration and memory loss in estrogen-deficient rats // Horm. Behav. 2 015. No 76. Р. 63-80.
  • Liu S., Wu H., Xue G., Ma X., Wu J., Qin Y., Hou Y. Metabolic alteration of neuroactive steroids and protective effect of progesterone in Alzheimer's disease-like rats // Neural. Regen. Res. 2013. Vol. 8, No 30. Р. 2800-2810.
  • Xu B., Yang R., Chang F., Chen L., Xie G., Sokabe M., Chen L. Neurosteroid PREGS protects neurite growth and survival of newborn neurons in the hippocampal dentate gyrus of APPswe/PS1dE9 mice // Curr. Alzheimer Res. 2012. Vol. 9, No 3. Р. 361-372.
  • Webber K.M., Stocco D.M., Casadesus G., Bowen R.L., Atwood C.S., Previll L.A., Harris P.L., Zhu X., Perry G., Smith M.A. Steroidogenic acute regulatory protein (StAR): evidence of gonadotropin-induced steroidogenesis in Alzheimer disease // Mol. Neurodegener. 2006. Vol. 1, No 14. Р. 1-14.
  • Liu T., Wimalasena J., Bowen R.L., Atwood C.S. Luteinizing hormone receptor mediates neuronal pregnenolone production via up-regulation of steroidogenic acute regulatory protein expression // J. Neurochem. 2007. Vol. 100, No 5. Р. 1329-1339.
  • Rosati F., Sturli N., Cungi M.C., Morello M., Villanelli F., Bartolucci G., Finocchi C., Peri A., Serio M., Danza G. Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cel // J. Steroid Biochem. Mol. Biol. 2011. Vol. 124, No 3-5. Р. 77-83.
  • Prange-Kiel J, Schmutterer T, Fester L, Zhou L., Imholz P., Brandt N., Vierk R, Jarry H., Rune G.M. Endocrine regulation of estrogen synthesis in the hippocampus? // Prog. Histochem. Cytochem. 2013. Vol. 48, No 2. Р. 49-64.
  • Berry A., Tomidokoro Y, Ghiso J., Thornton J. Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-beta levels in female rats // Horm. Behav. 2008. Vol. 54, No 1. Р. 143-152.
  • Burnham V, Sundby C, Laman-Maharg A., Thornton J. Luteinizing hormone acts at the hippocampus to dampen spatial memory // Horm. Behav. 2 017. No 89. Р. 55-63.
  • Blair J.A., Palm R, Chang J., McGee H, Zhu X., Wang X., Casadesus G. Luteinizing hormone downregulation but not estrogen replacement improves ovariectomy-associated cognition and spine density loss independently of treatment onset timing // Horm. Behav. 2 016. No 78. Р. 60-66.
  • Bryan K.J., Mudd J.C., Richardson S.L., Chang J., Lee H.G., Zhu X., Smith M.A., Casadesus G. Down-regulation of serum gonadotropins is as effective as estrogen replacement at improving menopause-associated cognitive deficits // J. Neurochem. 2010. Vol. 112, No 4. Р. 870-881.
  • Ziegler S.G., Thornton J.E. Low luteinizing hormone enhances spatial memory and has protective effects on memory loss in rats // Horm. Behav. 2 010. Vol. 58, No 5. Р. 705-713.
  • Casadesus G., Webber K.M., Atwood C.S., Pappolla M.A., Perry G., Bowen R.L., Smith M.A. Luteinizing hormone modulates cognition and amyloid-beta deposition in Alzheimer APP transgenic mice // Biochim. Biophys. Acta. 2006. Vol. 1762, No 4. Р. 447-452.
  • Barron A.M., Verdile G., Taddei K., Bates K.A., Martins R.N. Effect of chronic hCG administration on Alzheimer's-related cognition and A beta accumulation in PS1KI mice // Endocrinology. 2 010. Vol. 151, No 11. Р. 5380-5388.
  • Palm R., Chang J., Blair J., Garcia-Mesa Y., Lee H.G., Castellani R.J., Smith M.A., Zhu X., Casadesus G. Down-regulation of serum gonadotropins but not estrogen replacement improves cognition in aged-ovariectomized 3xTg-AD female mice // J. Neurochem. 2014. Vol. 130, No 1. Р. 115-125.
  • Rosario E.R., Carroll J.C., and Pike C.J. Evaluation of the effects of testosterone and luteinizing hormone on regulation of в-amyloid in male 3xTg-AD mice // Brain Res. 2012. Vol. 23, No 1466. Р. 137-145.
  • Nuruddin S., Syverstad G.H., Lillehaug S., Leergaard T.B., Nilsson L.N., Ropstad E., Krogens A., Haraldsen I.R., Torp R. Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaquebearing Alzheimer's disease transgenic mice // PLoS One. 2014. Vol. 9, No 8. Р. 603-607.
  • D'Amico A.V, Braccioforte M.H., Moran B.J., Chen M.H. Luteinizing-hormone releasing hormone therapy and the risk of death from Alzheimer disease // Alzheimer Dis. Assoc. Disord. 2010. Vol. 24, No 1. Р. 85-89.
  • Nead K.T., Gaskin G., Chester C., Swisher-McClure S., Leeper N.J., Shah N.H. Association Between Androgen Deprivation Therapy and Risk of Dementia // JAMA Oncol. 2017. Vol. 3, No 1. Р. 49-55.
  • Green H.J., Pakenham K.I., Headley B.C., Yaxley J., Nicol D.L., Mactaggart P.N., Swanson C., Watson R.B., Gardiner R.A. Altered cognitive function in men treated for prostate cancer with luteinizing hormone-releasing hormone analogues and cyproterone acetate: a randomized controlled trial // BJU Int. 2002. Vol. 90, No 4. Р. 427-432.
  • Morote J., Tabernero E.J., Alvarez Ossorio J.L., Ciria J.P., Domnnguez-Escrig J.L., Vazquez F., Angulo.J, Lypez F.J., de La Iglesia R., Romero J. The Effect of Luteinizing Hormone Reducing Agent on A nxiety and Novel Object Recognition Memory in Gonadectomized Rats // Basic Clin. Neurosci. 2017. Vol. 8, No 2. Р. 113-119.
  • Okamoto K., Sekine Y., and Nomura M. Koike H., Matsui H., Shibata Y., Ito K., Suzuki K. Effects of a luteinizing hormone-releasing hormone agonist on cognitive, sexual, and hormonal functions in patients with prostate cancer: relationship with testicular and adrenal androgen levels // Basic Clin. Androl. 2015. Vol. 25, No 3. Р. 30-33.
  • Wiechno P.J., Sadowska M., Kalinowski T., Michalski W., Demkow T. Does pharmacological castration as adjuvant therapy for prostate cancer after radiotherapy affect anxiety and depression levels, cognitive functions and quality of life? // Psychooncology. 2 013. Vol. 22, No 2. Р. 346-351.
  • Nedelec C., Ragot S., Irani J., Pires C., Gil R., Dorn B. Effects by androgen suppression with luteinizing hormone on cognitive functions in men treated for cancer of prostate // Prog. Urol. 2009. Vol. 19, No 1. Р. 47-53.
  • Jenkins V.A., Bloomfield D.J., Shilling V.M., and Edginton T.L. Does neoadjuvant hormone therapy for early prostate cancer affect cognition? Results from a pilot study // BJU Int. 2005. Vol. 96, No 1. Р. 48-53.
  • Jim H.S., Small B.J., Patterson S, Salup R, Jacobsen P.B. Cognitive impairment in men treated with luteinizing hormone-releasing hormone agonists for prostate cancer: a controlled comparison // Support Care Cancer. 2010. Vol. 18, No 1. Р. 21-27.
  • Rosin R.A., Raskind M.A. Gonadotrophin-releasing hormone agonist treatment of aggression in Alzheimer's disease: a case report // Int. Psychogeriatr. 2005. Vol. 17, No 2. Р. 313-318.
  • Bowen R.L., Perry G, Xiong C, Smith M.A., Atwood C.S. A clinical study of lupron depot in the treatment of women with Alzheimer's disease: preservation of cognitive function in patients taking an acetylcholinesterase inhibitor and treated with high dose lupron over 48 weeks // J. Alzheimers Dis. 2015. Vol. 44, No 2. Р. 549-560.
  • Шабанов П.Д., Сапронов H.C. ПcиxoнеLpoэндoкpинoлoгия. СПб.: Информ-Навигатор, 2010. 984 с. [Shabanov P.D., Sapronov N.S. Psychoneuroendocrinology. St. Petersburg: Izdatel’stvo Inform- Navigator, 2010. 984 p.].
  • Bailey M, Silver R. Sex Differences in Circadian Timing Systems: Implications for Disease // Front. Neuroendocrinol. 2014. Vol. 35, No 1. Р. 111-139.

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