Author(s): WANG, Y., WIRTZ, J., CEFIS, M., CHANEY, R., MELOUX, A., QUIRIE, A., PRIGENT-TESSIER, A., GARNIER, P., Institution: UNIVERSITÉ BOURGOGNE EUROPE, Country: FRANCE, Abstract-ID: 455

INTRODUCTION:
Physical exercise (EX) improves cognitive function and mental health by promoting hippocampal neurogenesis through increased brain-derived neurotrophic factor (BDNF) signaling, a critical regulator of neuroplasticity (1). According to the molecular mechanisms underlying EX-induced brain BDNF overproduction, muscle myokines induced by contraction (2), such as FNDC5/irisin, can cross the blood-brain barrier and modulate brain BDNF production through muscle-brain crosstalk. Electromyostimulation (EMS), which electrically activates skeletal muscle via an external current, may therefore act as an alternative therapy to mimic some effects of EX by engaging this muscle-brain dialogue, particularly in patients with disabilities. Our team has previously demonstrated that acute EMS (two sessions, one week apart) significantly elevates hippocampal BDNF and neuroplasticity-related protein expression in rats, enhances executive function, and reduces anxiety in humans (3). To determine whether these benefits could be amplified, the same protocol was applied in rats under chronic conditions.
METHODS:
Chronic EMS was applied to the quadriceps of 8-week-old male Wistar rats for 7 days (30 min/day; 40 Hz, 400 μs pulse width, 7 s ON/14 s OFF; intensity 6–20 mA). Behavioral assessments for anxiety- and depression-like behaviors were performed 24 h after the last EMS session, followed by collection of blood, hippocampus, and quadriceps for ELISA, Western blot, and immunofluorescence analyses.
RESULTS:
Surprisingly, chronic EMS reduced hippocampal BDNF and neuroplasticity-related protein levels, while increasing pro-inflammatory cytokine expression in both the hippocampus and blood. These changes were associated with microglial and astrocytic activation in the hippocampus. EMS-treated rats also displayed anxiety and depressive-like behaviors. At the muscular level, an increase in FNDC5/irisin muscular expression was observed, but no change in irisin blood and brain levels. Furthermore, EMS caused tissue damage and elevated pro-inflammatory cytokines, along with increased serum corticosterone.
CONCLUSION:
Our data highlight that increased muscle FNDC5/irisin expression does not always reflect beneficial muscle-brain dialogue. In contrast, stimulation conditions that induce muscle damage trigger muscle-derived inflammatory signals, leading to maladaptive communication to the brain, hippocampal neuroinflammation, and altered BDNF. These findings highlight the importance of optimizing muscle stimulation protocols to minimize muscle damage, particularly to individuals suffering from muscle weakness.