Luteinizing hormone downregulation but not estrogen replacement improves ovariectomy-associated cognition and spine density loss independently of treatment onset timing

Hormones and Behavior

Volumn 78, Issue , 2016, Pages 60-66

  Blair, Jeffrey A ^a   Palm, Russell ^b   Chang, Jaewon ^c   McGee, Henry ^a   Zhu, Xiongwei ^c   Wang, Xinglong ^c   Casadesus, Gemma ^a  

^a KENT STATE UNIVERSITY   (United States)

^b MEDICAL COLLEGE OF OHIO   (United States)

^c CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Aging; Cognition; Estrogen; Luteinizing hormone; Menopause; Ovariectomy; Spine density; Timing

Indexed keywords

ESTRADIOL; LEUPRORELIN; LUTEINIZING HORMONE; ESTROGEN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DENDRITIC SPINE; DENRITIC SPINE DENSITY; DISEASE ASSOCIATION; DOWN REGULATION; DRUG EFFICACY; ESTROGEN THERAPY; FEMALE; HORMONAL REGULATION; HORMONE ACTION; LEARNING; LUTEINIZING HORMONE BLOOD LEVEL; MORRIS WATER MAZE TEST; MOUSE; NERVE CELL PLASTICITY; NONHUMAN; OVARIECTOMY; POSTOPERATIVE COGNITIVE DYSFUNCTION; PRIORITY JOURNAL; SPATIAL MEMORY; TIME TO TREATMENT; ADVERSE EFFECTS; ANIMAL; BLOOD; BONE DENSITY; C57BL MOUSE; COGNITION; COGNITION DISORDERS; DRUG EFFECTS; OSTEOPOROSIS; PHYSIOLOGY; PSYCHOLOGY; REPRODUCTION; SPINE; TIME FACTOR;

ANIMALS; BONE DENSITY; COGNITION; COGNITION DISORDERS; DOWN-REGULATION; ESTRADIOL; ESTROGEN REPLACEMENT THERAPY; ESTROGENS; FEMALE; LUTEINIZING HORMONE; MICE, INBRED C57BL; OSTEOPOROSIS; OVARIECTOMY; REPRODUCTION; SPINE; TIME FACTORS;

EID: 84946422993     PISSN: 0018506X     EISSN: 10956867     Source Type: Journal    
DOI: 10.1016/j.yhbeh.2015.10.013     Document Type: Article

References (53)

1. Apaja P.M., Harju K.T., Aatsinki J.T., Petäjä-Repo U.E., Rajaniemi H.J. Identification and structural characterization of the neuronal luteinizing hormone receptor associated with sensory systems. J. Biol. Chem. 2004, 279(3):1899-1906.
2. Bailey M.E., Wang A.C., Hao J., Janssen W.G., Hara Y., Dumitriu D., Hof P.R., Morrison J.H. Interactive effects of age and estrogen on cortical neurons: implications for cognitive aging. Neuroscience 2011, 191:148-158.
3. Barnard L., Balen A.H., Ferriday D., Tiplady B., Dye L. Cognitive functioning in polycystic ovary syndrome. Psychoneuroendocrinology 2007, 32(8):906-914.
4. Barron A.M., Verdile G., Taddei K., Bates K.A., Martins R.N. Effect of chronic hCG administration on Alzheimer's-related cognition and Aβ accumulation in PS1KI mice. Endocrinology 2010, 151(11):5380-5388.
5. Berry A., Tomidokoro Y., Ghiso J., Thornton J. Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-β levels in female rats. Horm. Behav. 2008, 54(1):143-152.
6. Blair J.A., Bhatta S., McGee H., Casadesus Smith G. Luteinizing Hormone: Evidence for direct action in the CNS. Horm. Behav. 2015, (Pre-press).
7. Bloss E.B., Janssen W.G., Ohm D.T., Yuk F.J., Wadsworth S., Saardi K.M., Morrison J.H. Evidence for reduced experience-dependent dendritic spine plasticity in the aging prefrontal cortex. J. Neurosci. 2011, 31(21):7831-7839.
8. 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, 44(2):549-560.
9. Brinton R.D. The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications. Trends Neurosci. 2008, 31:529.
10. 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, 112(4):870-881.
11. Butchart J., Birch B., Bassily R., Wolfe L., Holmes C. Male sex hormones and systemic inflammation in Alzheimer disease. Alzheimer Dis. Assoc. Disord. 2013, 27(2):153-156.
12. 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-β deposition in Alzheimer APP transgenic mice. Biochim. Biophys. Acta (BBA) - Mol. Basis Dis. 2006, 1762(4):447-452.
13. Conway S., McCann S.M. The role of Lh in the autofeedback inhibition of Lh and Fsh secretion in ovariectomized rats. Endocr. Res. 1990, 16(3):403-413.
14. D'Agostino G., Russo R., Avagliano C., Cristiano C., Meli R., Calignano A. Palmitoylethanolamide protects against the amyloid-β25-35-induced learning and memory impairment in mice, an experimental model of Alzheimer disease. Neuropsychopharmacology 2012, 37(7):1784-1792.
15. Daniel J.M., Bohacek J. The critical period hypothesis of estrogen effects on cognition: insights from basic research. Biochim. Biophys. Acta 2010, 1800(10):1068-1076.
16. Daniel J.M., Hulst J.L., Berbling J.L. Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation. Endocrinology 2006, 147(1):607-614.
17. De Fiebre N.E., Sumien N., Forster M.J., De Fiebre C.M. Spatial learning and psychomotor performance of C57BL/6 mice: age sensitivity and reliability of individual differences. Age 2006, 28(3):235-253.
18. Emanuele N., Oslapas R., Connick E., Kirsteins L., Lawrence A.M. Hypothalamic LH may play a role in control of pituitary LH release. Neuroendocrinology 1981, 33(1):12-17.
19. Emanuele N.V., Anderson J., Andersen E., Connick E., Baker G., Kirsteins L., Lawrence A.M. Extrahypothalamic brain luteinizing hormone: characterization by radioimmunoassay, chromatography, radioligand assay and bioassay. Neuroendocrinology 1983, 36(4):254-260.
20. Fata J.E., Chaudhary V., Khokha R. Cellular turnover in the mammary gland is correlated with systemic levels of progesterone and not 17β-estradiol during the estrous cycle. Biol. Reprod. 2001, 65(3):680-688.
21. Gibbs R.B. Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol. Aging 2000, 21(1):107-116.
22. Gould E., Woolley C.S., Frankfurt M., McEwen B.S. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J. Neurosci. 1990, 10(4):1286-1291.
23. Gutierrez H., Davies A.M. Regulation of neural process growth, elaboration and structural plasticity by NF-κB. Trends Neurosci. 2011, 34(6):316-325.
24. Hämäläinen T., Poutanen M., Huhtaniemi I. Age-and sex-specific promoter function of a 2-kilobase 5'-flanking sequence of the murine luteinizing hormone receptor gene in transgenic mice. Endocrinology 1999, 140(11):5322-5329.
25. Heikkinen T., Puoliväli J., Tanila H. Effects of long-term ovariectomy and estrogen treatment on maze learning in aged mice. Exp. Gerontol. 2004, 39(9):1277-1283.
26. Heneka M.T., Kummer M.P., Stutz A., Delekate A., Schwartz S., Vieira-Saecker A., Griep A., Axt D., Remus A., Tzeng T., Gelpi E., Halle A., Korte M., Latz E., Golenbock D.T. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 2013, 493(7434):674-678.
27. Hostetter G., Gallo R.V., Brownfield M.S. Presence of immunoreactive luteinizing hormone in the rat forebrain. Neuroendocrinology 1981, 33(4):241-245.
28. Lei Z.M., Rao C.V., Kornyei J.L., Licht P., Hiatt E.S. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain. Endocrinology 1993, 132(5):2262-2270.
29. Lukacs H., Hiatt E.S., Lei Z.M., Rao C.V. Peripheral and intracerebroventricular administration of human chorionic gonadotropin alters several hippocampus-associated behaviors in cycling female rats. Horm. Behav. 1995, 29(1):42-58.
30. Mak G.K., Enwere E.K., Gregg C., Pakarainen T., Poutanen M., Huhtaniemi I., Weiss S. Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. Nat. Neurosci. 2007, 10(8):1003-1011.
31. McConnell S.E., Alla J., Wheat E., Romeo R.D., McEwen B., Thornton J.E. The role of testicular hormones and luteinizing hormone in spatial memory in adult male rats. Horm. Behav. 2012, 61(4):479-486.
32. McEwen B.S., Akama K.T., Spencer-Segal J.L., Milner T.A., Waters E.M. Estrogen effects on the brain: actions beyond the hypothalamus via novel mechanisms. Behav. Neurosci. 2012, 126(1):4-16.
33. McLaughlin K.J., Bimonte-Nelson H., Neisewander J.L., Conrad C.D. Assessment of estradiol influence on spatial tasks and hippocampal CA1 spines: evidence that the duration of hormone deprivation after ovariectomy compromises 17β-estradiol effectiveness in altering CA1 spines. Horm. Behav. 2008, 54(3):386-395.
34. Meng X.L., Rennert O.M., Chan W.Y. Human chorionic gonadotropin induces neuronal differentiation of PC12 cells through activation of stably expressed lutropin/choriogonadotropin receptor. Endocrinology 2007, 148(12):5865-5873.
35. Palm R., Chang J., Blair J., Garcia-Mesa Y., Lee H.G., Castellani R.J., Casadesus G. Down-regulation of serum gonadotropins but not estrogen replacement improves cognition in aged-ovariectomized 3xTg AD female mice. J. Neurochem. 2014, 130:115-125.
36. Rodrigues M.A., Verdile G., Foster J.K., Hogervorst E., Joesbury K., Dhaliwal S., Martins R.N. Gonadotropins and cognition in older women. J. Alzheimers Dis. 2008, 13(3):267-274.
37. Rodriguez A., Ehlenberger D.B., Dickstein D.L., Hof P.R., Wearne S.L. Automated three-dimensional detection and shape classification of dendritic spines from fluorescence microscopy images. PLoS One 2008, 3(4).
38. Schally A.V., Comaru-Schally A.M., Nagy A., Kovacs M., Szepeshazi K., Plonowski A., Halmos G. Hypothalamic hormones and cancer. Front. Neuroendocrinol. 2001, 22(4):248-291.
39. Sherwin B.B. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology 1988, 13(4):345-357.
40. Short R.A., O'Brien P.C., Graff-Radford N.R., Bowen R.L. Elevated gonadotropin levels in patients with Alzheimer disease. Mayo Clin. Proc. 2001, 76(9):906-909.
41. Staffend N.A., Meisel R.L. DiOlistic labeling of neurons in tissue slices: a qualitative and quantitative analysis of methodological variations. Front. Neuroanat. 2011, 5:14.
42. Tanapat P., Hastings N.B., Reeves A.J., Gould E. Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J. Neurosci. 1999, 19(14):5792-5801.
43. Telegdy G., Tanaka M., Schally A.V. Effects of the LHRH antagonist cetrorelix on the brain function in mice. Neuropeptides 2009, 43(3):229-234.
44. Telegdy G., Adamik A., Tanaka M., Schally A.V. Effects of the LHRH antagonist cetrorelix on affective and cognitive functions in rats. Regul. Pept. 2010, 159(1):142-147.
45. Verdile G., Yeap B.B., Clarnette R.M., Dhaliwal S., Burkhardt M.S., Chubb S.P., Martins R.N. Luteinizing hormone levels are positively correlated with plasma amyloid-β protein levels in elderly men. J. Alzheimers Dis. 2008, 14(2):201-208.
46. Verdile G., Laws S.M., Henley D., Ames D., Bush A.I., Ellis K.A., Martins R.N. Associations between gonadotropins, testosterone and β amyloid in men at risk of Alzheimer's disease. Mol. Psychiatry 2014, 19:69-75.
47. Walter J., Keiner S., Witte O.W., Redecker C. Age-related effects on hippocampal precursor cell subpopulations and neurogenesis. Neurobiol. Aging 2011, 32(10):1906-1914.
48. Waters E.M., Mitterling K., Spencer J.L., Mazid S., McEwen B.S., Milner T.A. Estrogen receptor alpha and beta specific agonists regulate expression of synaptic proteins in rat hippocampus. Brain Res. 2009, 1290:1-11.
49. Wood G.A., Fata J.E., Watson K.L., Khokha R. Circulating hormones and estrous stage predict cellular and stromal remodeling in murine uterus. Reproduction 2007, 133(5):1035-1044.
50. Woolley C.S., McEwen B.S. Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J. Neurosci. 1992, 12(7):2549-2554.
51. Yang E.J., Nasipak B.T., Kelley D.B. Direct action of gonadotropin in brain integrates behavioral and reproductive functions. Proc. Natl. Acad. Sci. 2007, 104(7):2477-2482.
52. Yen S.S., Vela P., Rankin J. Inappropriate secretion of follicle-stimulating hormone and luteinizing hormone in polycystic ovarian disease. J. Clin. Endocrinol. Metab. 1970, 30(4):435-442.
53. Ziegler S.G., Thornton J.E. Low luteinizing hormone enhances spatial memory and has protective effects on memory loss in rats. Hormones and behavior 2010, 58(5):705-713.