Altered expression of Alzheimer's disease-related proteins in male hypogonadal mice

E.S. Drummond; R.N. Martins; D.J. Handelsman; A.R. Harvey

doi:10.1210/en.2011-2003

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Altered expression of Alzheimer's disease-related proteins in male hypogonadal mice

Journal article

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Peer reviewed

Altered expression of Alzheimer's disease-related proteins in male hypogonadal mice

E.S. Drummond, R.N. Martins, D.J. Handelsman and A.R. Harvey

Endocrinology, Vol.153(6), pp.2789-2799

2012

DOI: https://doi.org/10.1210/en.2011-2003

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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 lifelong 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 beta-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-1 beta 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.

Details

Title: Altered expression of Alzheimer's disease-related proteins in male hypogonadal mice
Authors/Creators: E.S. Drummond (Author/Creator) - The University of Western Australia
R.N. Martins (Author/Creator) - The University of Western Australia
D.J. Handelsman (Author/Creator) - Anzac Research Institute
A.R. Harvey (Author/Creator) - The University of Western Australia
Publication Details: Endocrinology, Vol.153(6), pp.2789-2799
Publisher: The Endocrine Society
Identifiers: 991005543210307891
Murdoch Affiliation: School of Veterinary and Biomedical Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.5 Neuroscience; 1.5.987 Neurosteroids
Web Of Science research areas: Endocrinology & Metabolism
ESI research areas: Biology & Biochemistry