Related Experiment Video
Updated: May 15, 2025
Orienteering as a Tool for Cognitive Research: An Implementation Guide
Published on: November 29, 2024
Aerobic Exercise Restores Hippocampal Neurogenesis and Cognitive Function by Decreasing Microglia Inflammasome
Renqing Zhao1, Xin Tian1, Haocheng Xu1
1College of Physical Education, Yangzhou University, Yangzhou, China.
Abstract:
Persistent microglial inflammation is a detrimental contributor to the progression of Parkinson disease (PD) pathology and related issues such as impaired adult hippocampal neurogenesis (AHN) and cognition. We conducted a 10-week exercise program with MPTP-treated mice to determine whether neuroinflammation can be addressed by aerobic exercise and elucidate its underlying regulatory mechanisms. Ten weeks of exercise significantly reduced PD-related pathology and enhanced AHN and memory. These changes were linked to a reduction in neuronal apoptosis, microglial inflammation, and NLRP3 inflammasome activation. In cultured microglia, fibril α-synuclein reduced FNDC5/irisin protein levels and induced NLRP3 inflammasome formation and IL-1β production, which could be diminished by recombinant irisin treatment. Interestingly, "runner serum" isolated from exercising rodents enhanced FNDC5/irisin expression and reduced NLRP3 inflammasome components and IL-1β secretion in α-synuclein-treated microglia. These effects could be diminished by blocking irisin signaling with cyclo RGDyk or NLRP3 agonist, nigericin sodium salt. Exercise-induced neuroprotective effects were weakened by treatment of MPTP-treated mice with cyclo RGDyk. In contrast, systematic administration of irisin partially replicated the beneficial effects of exercise on PD pathology, AHN, and memory function. As a nonpharmacological strategy, aerobic exercise effectively addresses PD pathology and preserves adult neurogenesis and cognition by mitigating microglial inflammation via mediating irisin/NLRP3 inflammasome pathways.
Insights
Aerobic exercise reduces Parkinson disease pathology by mitigating microglial inflammation. This nonpharmacological approach enhances neurogenesis and cognition through the irisin/NLRP3 inflammasome pathway.
Area of Science:
- Neuroscience
- Immunology
- Exercise Physiology
Background:
- Persistent microglial inflammation exacerbates Parkinson disease (PD) pathology and impairs adult hippocampal neurogenesis (AHN) and cognition.
- Understanding the mechanisms by which exercise impacts neuroinflammation is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the effects of aerobic exercise on neuroinflammation in a mouse model of Parkinson disease.
- To elucidate the underlying regulatory mechanisms, focusing on the irisin/NLRP3 inflammasome pathway.
Main Methods:
- MPTP-treated mice underwent a 10-week aerobic exercise program.
- In vitro studies utilized cultured microglia treated with α-synuclein, irisin, or runner serum.
- Key molecular markers of inflammation, apoptosis, and neurogenesis were assessed.
Main Results:
- Exercise significantly reduced PD pathology, neuronal apoptosis, microglial inflammation, and NLRP3 inflammasome activation, while enhancing AHN and memory.
- α-synuclein reduced FNDC5/irisin and induced NLRP3 inflammasome activation; recombinant irisin and runner serum reversed these effects.
- Irisin signaling and NLRP3 inflammasome activation were identified as critical mediators of exercise's neuroprotective effects.
Conclusions:
- Aerobic exercise is a potent nonpharmacological strategy for mitigating microglial inflammation in Parkinson disease.
- Exercise preserves adult neurogenesis and cognitive function by modulating the irisin/NLRP3 inflammasome pathway.
- Irisin administration partially replicated the beneficial effects of exercise, highlighting its therapeutic potential.
