高壓氧治療SCA17小鼠之持久性、再現性、強度與分子效應

We have established SCA17 transgenic mouse model which shows phenotypes similar to the clinical patients and could be used to evaluate potential therapeutic treatments for SCA17. Hyperbaric oxygen treatment (HBOT) is considered to be a less invasive therapy for many conditions. Our previous studies indicate that oxidative stress, neuroinflammation and neuronal apoptosis are elevated in the SCA17 mice, which are the main targets of HBOT. Therefore, we expect HBOT to be a therapeutic option for the management of SCA17. We first Identified the lasting effect of HBOT (2.2 ATA for 14 days) on SCA17 mice. Behavior tasks were conducted on the mice before HBO, right after HBOT and every month thereafter to examine how long the beneficial effect could be lasted in these mice. We then investigated whether the beneficial effect of one more cycle of HBOT in HBO-treated mice. The protein quantitative and histopathological staining analyses show that HBOT can promote CMA, reduce PC death, and inhibit nerve inflammation in SCA17 TG mice, which further improve cognition. In addition, oxidative stress test, complete blood count test, blood biochemistry and the results of liver, and kidney pathological examination indicated that HBOT is a safe treatment. HBOT could be potential to be developed into an alternative or therapeutic treatment for SCA17. Accumulated experimental findings have revealed the similarity in disease pathomechanisms and possible therapeutic strategies in polyQ diseases, therefore HBO could be potential alternative or therapeutic treatment for other polyQ diseases caused by chronic genetic mutations other than SCA17.