Hearing modulation affects Alzheimer's disease progression linked to brain inflammation: a study in mouse models

Area of Science:

• Neuroscience
• Gerontology
• Pathology

Background:

• Hearing loss (HL) is a significant risk factor for Alzheimer's disease (AD) onset.
• Mechanisms linking HL to AD pathogenesis remain incompletely understood.
• This study investigates the impact of drug-induced hearing loss (DIHL) on AD-related protein expression in mouse models.

Purpose of the Study:

• To explore the effects of DIHL on beta-amyloid (Aβ) accumulation in AD mouse models.
• To assess the impact of DIHL on neuroinflammation markers, including glial activation and cytokine expression.
• To examine the role of the mammalian target of rapamycin (mTOR) pathway in HL-associated AD progression.

Main Methods:

• Drug-induced hearing loss (DIHL) was established in 5xFAD and Tg2576 mice using kanamycin and furosemide.
• Beta-amyloid (Aβ) accumulation was quantified via immunohistochemistry and immunoblotting.
• Expression of neuroinflammatory markers (Iba1, GFAP, IL-1β, IL-6, TNF-α) and mTOR pathway proteins (mTOR, p70S6K, S6) was analyzed.

Main Results:

• DIHL significantly increased Aβ deposition in the hippocampus and cortex.
• Elevated levels of microglial (Iba1) and astrocyte (GFAP) activation were observed.
• Increased expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and heightened mTOR pathway activity (p-mTOR, p-p70S6K, p-S6) were detected.

Conclusions:

• Hearing loss exacerbates Aβ accumulation and neuroinflammation in the brain.
• HL independently contributes to neuroinflammation by activating microglia and astrocytes.
• Targeting hearing loss presents a potential strategy for mitigating Alzheimer's disease risk.