Auditory or Audiovisual Stimulation Ameliorates Cognitive Impairment and Neuropathology in ApoE4 Knock-In Mice

Abstract

We hypothesized that auditory stimulation could reduce the progression of Alzheimer’s disease (AD), and that audiovisual stimulation could have additional effects through multisensory integration. We exposed 12 month old Apoetm1.1(APOE*4)Adiuj mice (a mouse model of sporadic AD) to auditory (A) or audiovisual stimulation (AV) at 40 Hz for 14 days in a soundproof chamber system (no stimulation, N). Behavioral tests were performed before and after each session, and their brain tissues were assessed for amyloid-beta expression and apoptotic cell death, after 14 days. Furthermore, brain levels of acetylcholine and apoptosis-related proteins were analyzed. In the Y-maze test, the percentage relative alternation was significantly higher in group A than in group N mice. Amyloid-beta and TUNEL positivity in the hippocampal CA3 region was significantly lower in group A and group AV mice than in group N mice (p < 0.05). Acetylcholine levels were significantly higher in group A and group AV mice than in group N mice (p < 0.05). Compared to group N mice, expression of the proapoptotic proteins Bax and caspase-3 was lower in group A, and expression of the antiapoptotic protein Bcl-2 was higher in group AV. In a mouse model of early-stage sporadic AD, auditory or audiovisual stimulation improved cognitive performance and neuropathology.

CD2AP is Co-Expressed with Tropomyosin-Related Kinase A and Ras-Related Protein Rab-5A in Cholinergic Neurons of the Murine Basal Forebrain

“…Concurrently, CD2AP was identified as a genetic risk factor for the development of AD in humans (Hollingworth et al, 2011;Naj et al, 2011), a finding that has been supported by a substantial number of studies across model organism species, including Mus musculus (Vandal et al, 2022), Drosophila (Ojelade et al, 2019;Shulman et al, 2014), and Caenorhabditis elegans (Alvarez et al, 2022;Kim et al, 2018). Previously established Cd2ap variants have even been incorporated along with variants in Trem2 em1Adiuj , App em1Adiuj and Apoe tm1.1(APOE*4)Adiuj into a multi-genetic/causal, humanized mouse model of AD (JAX Strain# 033873) (Jung et al, 2023;Pandey et al, 2023).…”

Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults

“…Environmental enrichment also has more specifically been shown to ameliorate the human-like cognitive decline in animal models of aging ( Valero et al, 2011 ; Patel, 2012 ). In lab animals, enhanced visual ( Iaccarino et al, 2016 ), auditory ( Martorell et al, 2019 ; Jung et al, 2023 ), and mastication ( de Siqueira Mendes et al, 2021 ) stimulation, facilitates memory as it does in human older adults ( Leon and Woo, 2018 ; Chan et al, 2022 ).…”