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This study investigated whether seven consecutive days of neuromuscular electrical stimulation (NMES) applied to rat quadriceps muscles would replicate the beneficial brain effects seen after single sessions. Instead of improving brain health markers, repeated NMES caused muscle damage, systemic inflammation, elevated stress hormones, and hippocampal changes including reduced mature BDNF levels, increased neuroinflammation, and altered synaptic proteins. These negative changes were accompanied by increased anxiety-like and depression-like behaviors in the animals, suggesting that frequent NMES sessions without adequate recovery time trigger maladaptive rather than beneficial muscle-to-brain signaling.
Why it matters
NMES is increasingly used clinically to maintain muscle function in patients who cannot exercise voluntarily, such as those in intensive care or with mobility limitations. This research suggests that daily application without sufficient recovery may harm rather than help brain function, highlighting the need to establish safe protocols with appropriate rest intervals before recommending repeated NMES as an exercise substitute.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Objective. Neuromuscular electrical stimulation (NMES) is increasingly used to preserve or restore muscle function in patients unable to exercise, and acute NMES improves cognitive performance and increases hippocampal mature brain-derived neurotrophic factor (BDNF). However, the consequences of repeated sessions for muscle-to-brain signaling remain poorly understood. We examined whether seven consecutive days of quadriceps NMES would reproduce this acute response. Methods. Male Wistar rats received daily 30-min quadriceps NMES or SHAM sessions under isoflurane for seven consecutive days. Blood was collected immediately after the final session and 24 h later, when muscle and hippocampal tissues were also collected. An independent cohort underwent behavioral testing. Results. Repeated NMES increased serum creatine kinase activity and quadriceps fibrillar collagen deposition without altering muscle mass, myofiber size, or degeneration-regeneration markers. These changes were accompanied by low-grade systemic inflammation and corticosterone elevation persisting 24 h after the final session. In the hippocampus, NMES increased inflammatory cytokine expression, astrocytic and microglial markers, and glucocorticoid receptor phosphorylation. Mature BDNF, TrkB phosphorylation and ERK1/2 signaling decreased, whereas proBDNF, p75NTR and JNK signaling increased; Akt and mTOR phosphorylation were unchanged. Synaptophysin, GAP43 and PSD95 also decreased. NMES increased marble burying and forced-swim immobility, without detectable changes in locomotion, recognition memory, or neuronal profile density. Conclusions. Repeated daily NMES engaged a distinct, maladaptive mode of muscle-to-brain signaling rather than reproducing the benefits reported after acute stimulation. Stimulation parameters and recovery intervals that avoid this response need to be defined before repeated NMES can be recommended as an exercise substitute.
Source: Repeated Neuromuscular Electrical Stimulation Protocol Disrupts Muscle-to-Brain Signaling in Rats