Bee venom phospholipase A2 ameliorates amyotrophic lateral sclerosis by increasing regulatory T cell population

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects the nerve cells responsible for controlling voluntary muscle movement in the brain and spinal cord, causing loss of muscle control. Moreover, other researchers have reported that BV phospholipase A2 (bvPLA2) has neuroprotective effects in a mouse model of Alzheimer’s disease (AD). The aim of this study was to investigate whether bvPLA2 alleviates the pathological features of ALS by affecting Tregs in SOD1 mice. SOD1-G93A mice were used as the ALS model. The mice (75-days old) were administered phosphate buffered saline (PBS) or bvPLA2 (0.5 mg/kg) twice a week. The results demonstrated that the body and hindlimb weights of PBS-treated SOD1 mice were lower than those of wild-type mice, whereas that of bvPLA2-treated SOD1 mice increased compared to that of PBS-treated SOD1 mice. Motor function also decreased to a lesser extent in bvPLA2-treated SOD1 mice, whereas that of PBS-treated SOD1 mice was significantly impaired compared to wild-type mice. Moreover, bvPLA2-treated SOD1 mice had greater number of intact motor neurons in their lumbar spinal cord compared to PBS-treated SOD1 mice. The level of Tregs in the TA muscle was also higher in bvPLA2-treated SOD1 mice than in PBS-treated SOD1 mice. Lastly, bvPLA2-treated SOD1 mice showed less increase in levels of NOS2 and TNF-α and lower levels of IL-4 and IL-10 compared to PBS-treated SOD1 mice. Thus, our data suggest that bvPLA2 alleviates the progress of ALS by inducing a Treg-mediated anti-inflammatory response.