| First Author | He W | Year | 2025 |
| Journal | J Neuroinflammation | Volume | 22 |
| Issue | 1 | Pages | 301 |
| PubMed ID | 41299682 | Mgi Jnum | J:378716 |
| Mgi Id | MGI:8274009 | Doi | 10.1186/s12974-025-03640-y |
| Citation | He W, et al. (2025) Post-onset intermittent fasting attenuates neuroinflammation and demyelination via a TRIB3-PERK-autophagy axis in an EAE model of multiple sclerosis. J Neuroinflammation 22(1):301 |
| abstractText | Prior studies have demonstrated therapeutic benefits of intermittent fasting (IF) in experimental autoimmune encephalomyelitis (EAE), yet they have predominantly examined prophylactic protocols or implemented short-term post-induction interventions, leaving the therapeutic window undefined and the underlying mechanisms unelucidated. Here, we systematically evaluate intermittent fasting (IF) initiated at a clinically critical juncture of 10 days post-induction (EAE_postIF), which coincides with early symptom onset, demonstrating significant attenuation of disease progression, reduced neuroinflammation, and preserved myelin integrity. Mechanistically, EAE_postIF activates a TRIB3-PERK-autophagy axis in the spinal cord, evidenced by increased ATF4, CHOP, and TRIB3 expression and suppression of mTOR signaling. In TRIB3-deficient mice, the beneficial effects of IF are partially attenuated, with clinical and histological improvements reduced relative to wild-type controls yet remaining superior to untreated cohorts. These findings establish a well-defined therapeutic window for IF intervention in neuroinflammation and identify TRIB3-PERK-autophagy signaling as a critical mediator, supporting IF as a viable metabolic strategy to complement existing MS therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-025-03640-y. |
