Cognitive impairment and prefrontal TGF-β1 elevation in a rat model of fatigue

Chronic fatigue syndrome (CFS) is a complex disorder of unknown etiology, characterized by persistent fatigue unrelieved by rest and accompanied by cognitive dysfunction. While dysregulated cytokines are implicated in CFS pathogenesis, the role of anti-inflammatory transforming growth factor β1 (TGF-β1) remains poorly defined.

This study investigated central and peripheral TGF-β1 dysregulation and cognitive function in a rat model of fatigue induced by 10-day repetitive sleep deprivation with intermittent rest. Rats were randomly divided into the control group and the fatigue group. Behavioral tests including open field test and Y-maze test were performed after the end of fatigue-loading procedure. Peripheral and central TGF-β1 levels were detected.

Rats in the fatigue group exhibited unchanged daytime short-term locomotor activity but significantly increased anxiety-like behavior in the open field test. In the Y-maze test, the fatigue group showed markedly reduced spontaneous alternation rates compared to controls. Furthermore, prefrontal cortical TGF-β1 levels were elevated in fatigued rats, whereas neither peripheral nor striatal TGF-β1 differed between groups.

These findings demonstrate that the 10-day repetitive sleep deprivation with intermittent rest fatigue model induces cognitive impairment and increased anxiety-like behavior, with selective prefrontal TGF-β1 upregulation. The concomitant elevation of prefrontal TGF-β1 and cognitive deficits suggests a potential role for central TGF-β1 signaling in the pathophysiology of mental fatigue, although the precise nature of this relationship remains to be elucidated.