title: Altered expression of Alzheimer's disease-related proteins in male hypogonadal mice.
abstract: Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in life-long deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and β-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the hippocampus and were not evident in the cerebellum or other brain tissues. Male hpg mice tended to have lower levels of IL-1β protein than male littermate controls. Immunohistochemical staining of the basal forebrain revealed that male hpg mice had lower choline acetyltransferase levels per neuron compared with controls. These AD-like changes specific to male hpg mice supports a link between androgen depletion and the development of AD pathology.
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Western Australia, 6009 Australia. E.Drummond@murdoch.edu.au
authors.forename: Eleanor S
authors.initials: ES
authors.lastname: Drummond
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
authors.forename: Alan R
authors.initials: AR
authors.lastname: Harvey
mesh_terms: D000367:Age Factors; D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D006062:Gonadotropins / Q000172:deficiency; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000378:metabolism*; D012737:Sex Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D006062:Gonadotropins; D053583:Interleukin-1beta; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); D007987:Gonadotropin-Releasing Hormone