Neuroscience Letters · Oct 19, 2026

Endpoint-specific interactions between aerobic exercise and benfotiamine in chronic noise-induced prefrontal cortical dysfunction in mice

By Ziari HA, Shaki F, Seyedabadi M et al.

Chronic environmental noise can impair brain redox and inflammatory homeostasis, but the effects of combined non-pharmacological and metabolic interventions remain unclear. This study investigated whether aerobic exercise and benfotiamine, separately or combined, attenuate noise-induced behavioral dysfunction and prefrontal cortical injury-related changes. Male Swiss albino mice were assigned to Control, Noise, Noise + aerobic exercise, Noise + benfotiamine (200 mg/kg/day), Noise + aerobic exercise + benfotiamine, or Noise + N-acetylcysteine (500 mg/kg/day) groups (n = 9/group). Noise-exposed mice received broadband industrial noise at 90 dB sound pressure level for 4 h/day for 28 days. Behavioral despair-like phenotypes, cortical redox status, inflammatory gene expression, and histopathology were evaluated. Noise increased immobility in the forced swim and tail suspension tests, elevated reactive oxygen species, nitric oxide, malondialdehyde, protein carbonyls, and pro-inflammatory transcripts, and reduced glutathione and antioxidant capacity. Both interventions attenuated multiple abnormalities. Aerobic exercise produced prominent behavioral effects and increased interleukin-10 expression, whereas benfotiamine strongly reduced reactive oxygen species, lipid peroxidation, and interleukin-1β. Significant exercise × benfotiamine interactions occurred for both behavioral tests, reactive oxygen species, tumor necrosis factor-α, interleukin-1β, and interleukin-10, but not for several other endpoints. The combined intervention frequently produced the most favorable absolute values, although significant interactions were generally subadditive rather than synergistic. Aerobic exercise and benfotiamine therefore provide broad but endpoint-specific protection against chronic noise-associated prefrontal cortical dysfunction.

doi.org/10.1016/j.neulet.2026.138765PubMed 42896818Interventions