Early Evidence of Low Bone Density and Decreased Serotonergic Synthesis in the Dorsal Raphe of a Tauopathy Model of Alzheimer's Disease.

Title

Early Evidence of Low Bone Density and Decreased Serotonergic Synthesis in the Dorsal Raphe of a Tauopathy Model of Alzheimer's Disease.

Creator

Dengler-Crish Christine M; Smith Matthew A; Wilson Gina N

Publisher

Journal of Alzheimer's disease : JAD

Date

2017
1905-07

Description

Reduced bone mineral density (BMD) and its clinical sequelae, osteoporosis, occur at a much greater rate in patients with Alzheimer's disease (AD), often emerging early in the disease before significant cognitive decline is seen. Reduced BMD translates to increased bone fracture risk, decreased quality of life, and increased mortality for AD patients. However, the mechanism responsible for this observation is unclear. We hypothesize that bone loss is an additional component of an AD prodrome-changes that emerge prior to dementia and are mediated by dysfunction of the central serotonergic pathways. We characterized the skeletal phenotype of htau mice that express human forms of the microtubule-associated protein tau that become pathologically hyperphosphorylated in AD. Using radiographic densitometry, we measured BMD in female and male htau mice from 2-6 months of age-time-points prior to the presence of significant tauopathy in the hippocampal/entorhinal regions characteristic of this model. We found a significantly reduced BMD phenotype in htau mice that was most pronounced in males. Using western blotting and immunofluorescence, we showed overall reduced tryptophan hydroxylase (TPH) protein in htau brainstem and a 70% reduction in

Subject

Female; Male; Animals; Mice; *Alzheimer's disease; Body Weight; Body Composition; Age Factors; Body Weight/genetics; Phosphorylation; Bone Density/*physiology; *Alzheimer Disease/complications/genetics/pathology; *bone density; *microtubule-associated protein; *serotonin; *tau proteins; *tauopathies; Body Composition/genetics; Bone Diseases/*etiology; Dorsal Raphe Nucleus/*pathology; Neurons/metabolism/pathology; Serotonin/*metabolism; tau Proteins/*genetics/metabolism; Tauopathies/complications/genetics; Tryptophan Hydroxylase/metabolism; Biological; Models; Inbred C57BL; Animal; Disease Models; Transgenic; Nerve Tissue Proteins; Neurodegenerative Diseases; Animal Studies; Alzheimer's Disease; Bone Density – Physiology; Nerve Tissue Proteins – Metabolism; Neurodegenerative Diseases – Complications; Alzheimer's Disease – Complications; Alzheimer's Disease – Pathology; Bone Diseases – Etiology; Brain Stem – Pathology; Neurons – Metabolism; Neurons – Pathology; Oxidoreductases – Metabolism; Serotonin – Metabolism

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1605–1619

Issue

4

Volume

55

Citation

Dengler-Crish Christine M; Smith Matthew A; Wilson Gina N, “Early Evidence of Low Bone Density and Decreased Serotonergic Synthesis in the Dorsal Raphe of a Tauopathy Model of Alzheimer's Disease.,” NEOMED Bibliography Database, accessed January 25, 2021, https://neomed.omeka.net/items/show/5120.

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