Work

Impaired prepulse inhibition in APP/PS1 mice is accompanied by substantial morphological changes in neurons of the central auditory system and hippocampus

Year: 2025

Type: article

Abstract: Auditory dysfunction is increasingly recognized as a non-cognitive feature of Alzheimer's disease (AD). We examined auditory processing and neuronal morphology in APPswe/PSEN1dE9 (APP/PS1) transgenic mice, a model of AD. Ten-month-old male APP/PS1 and wild-type (WT) littermates were tested for auditory thresholds using auditory brainstem responses (ABR) and for sensorimotor gating using prepulse inhibition (PPI) of the acoustic startle reflex. ABR thresholds did not differ between groups across tested frequencies (2-16 kHz), indicating preserved peripheral hearing. In contrast, APP/PS1 mice showed significantly impaired PPI at 4, 12, and 20 kHz prepulses and displayed exaggerated startle responses to high-intensity stimuli. Exploratory and anxiety-like behavior, assessed in the open field and elevated plus maze, did not differ between groups. Morphological analysis of Golgi-Cox-stained neurons revealed widespread dendritic pathology in the inferior colliculus, medial geniculate body and auditory cortex, as well as in hippocampal CA1. Compared with WT, APP/PS1 neurons exhibited shorter dendrites, reduced branching, and lower spine density, accompanied by markedly decreased dendritic complexity in Sholl analyses. These findings demonstrate that sensorimotor gating deficits in APP/PS1 mice are accompanied by degeneration in central auditory and hippocampal circuits; however, a contribution of peripheral degeneration cannot be excluded. The data highlights the vulnerability of auditory midbrain and thalamic structures in this model of AD and suggests that dendritic alterations along the auditory pathway may contribute to central auditory dysfunction and serve as potential early biomarkers of disease.

Source: Hearing Research

DOI: 10.1016/j.heares.2025.109484