Theta-shaking mitigates cognitive-emotional decline via subiculum and ventral septum metabolic plasticity.

Authors

Runhong Yao, Kouji Yamada, Hirohide Sawada, Takeshi Chihara, Naoki Aizu, Kazuhiro Nishii

Published in

Mechanobiology in medicine. Volume 3. Issue 4. Pages 100148. Epub Aug 22, 2025.

Abstract

Aging-associated cognitive decline remains a major challenge in gerontology; few non-invasive interventions provide both mechanistic insight and translational feasibility. We investigated whether low-frequency "theta-shaking" whole-body vibration (5 ​Hz) could modulate cognitive function, emotional behavior, and metabolic plasticity in a senescence-accelerated mouse model. Senescence-accelerated mouse prone-10 mice were exposed to theta-shaking stimulation for 30 weeks. Spatial memory was assessed using Y-maze spontaneous alternation test, and anxiety-related behavior was evaluated using marble burying test. Histological and immunohistochemical analyses were conducted to assess neuronal density and protein expression in specific brain regions. Theta-shaking subjected mice exhibited delayed yet significant improvements in spatial memory at 20 (p ​= ​0.017) and 30 (p ​= ​0.018) weeks. Anxiety-related behavior shows a biphasic pattern: an initial increase at 20 weeks (p ​< ​0.001) followed by stabilization at 30 weeks. Histological analysis revealed preserved neuronal density in the subiculum (p ​< ​0.001) and elevated proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression in the Cornu Ammonis 1, subiculum, and lateral septum (all p ​< ​0.05). Notably, mitochondrial biogenesis appeared to be intervention's primary target, as shown by robust PGC1α upregulation, while brain-derived neurotrophic factor revealed a trend-level increase (p ​= ​0.062), and neurotrophin-3 expression remained unchanged. Frequency-tuned mechanical stimulation induced region-specific neural neurometabolic adaptations, supporting theta-shaking as a non-pharmacological, low-exertion strategy to counteract brain aging. These findings offer promising translational potential, especially for individuals with limited mobility.

PMID:
40995564
Bibliographic data and abstract were imported from PubMed on 25 Sep 2025.

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