Abstract
Non-genetic environmental hazards are thought to be associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. Aging and chronic noise exposure have been considered important factors in the AD. Here, we investigated the impact of chronic noise exposure on the AD-like neuropathology in the senescence-accelerated prone mouse (SAMP8) and the underlying mechanisms of such effects. We examined the consequences of AD-like neuropathology in 3-month-old SAMP8 mice using low- and high-intensity noise exposure and 8-month-old SAMP8 mice as aging positive controls. Immunoblotting and immunohistochemistry were conducted to examine AD-like pathological changes and potential mechanisms. Chronic noise exposure led to progressive overproduction of Aβ and increased the hyperphosphorylation of tau at Ser396, Thr205, and Thr231 sites in the hippocampus and the prefrontal cortex (PFC) in young SAMP8 mice, similar to that observed in aging SAMP8 mice. Both noise exposure and aging could cause a significant downregulation in Wnt signaling expression. These findings demonstrate that chronic noise stress exacerbated AD-like neuropathology, possibly by disrupting Wnt signaling and triggering aberrant tau hyperphosphorylation and Aβ in the PFC and hippocampus.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aging / genetics*
-
Aging / metabolism
-
Aging / pathology
-
Alzheimer Disease / etiology
-
Alzheimer Disease / genetics*
-
Alzheimer Disease / metabolism
-
Alzheimer Disease / pathology
-
Amyloid beta-Peptides / genetics*
-
Amyloid beta-Peptides / metabolism
-
Animals
-
Disease Models, Animal
-
Dishevelled Proteins / genetics
-
Dishevelled Proteins / metabolism
-
Environmental Exposure / adverse effects
-
Gene Expression Regulation, Developmental
-
Glycogen Synthase Kinase 3 beta / genetics
-
Glycogen Synthase Kinase 3 beta / metabolism
-
Hippocampus / metabolism
-
Hippocampus / pathology
-
Intercellular Signaling Peptides and Proteins / genetics
-
Intercellular Signaling Peptides and Proteins / metabolism
-
Male
-
Mice
-
Mice, Transgenic
-
Noise / adverse effects*
-
Peptide Fragments / genetics*
-
Peptide Fragments / metabolism
-
Phosphorylation
-
Prefrontal Cortex / metabolism
-
Prefrontal Cortex / pathology
-
Tumor Suppressor Protein p53 / genetics
-
Tumor Suppressor Protein p53 / metabolism
-
Wnt Signaling Pathway*
-
beta Catenin / genetics
-
beta Catenin / metabolism
-
tau Proteins / genetics*
-
tau Proteins / metabolism
Substances
-
Amyloid beta-Peptides
-
CTNNB1 protein, mouse
-
Dishevelled Proteins
-
Dkk1 protein, mouse
-
Dvl1 protein, mouse
-
Intercellular Signaling Peptides and Proteins
-
Mapt protein, mouse
-
Peptide Fragments
-
Tumor Suppressor Protein p53
-
amyloid beta-protein (1-40)
-
amyloid beta-protein (1-42)
-
beta Catenin
-
tau Proteins
-
Glycogen Synthase Kinase 3 beta