Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

Intestinal Dopamine Receptor D2 is Required for Neuroprotection Against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Dopaminergic Neurodegeneration

A wealth of evidence has suggested that gastrointestinal dysfunction is associated with the onset and progression of Parkinson’s disease(PD).However,the mechanisms underlying these links remain to be defined.Here,we investigated the impact of deregulation of intestinal dopamine D2 receptor(DRD2)signaling in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced dopaminergic neurodegeneration.Dopamine/dopamine signaling in the mouse colon decreased with ageing.Selective ablation of Drd2,but not Drd4,in the intestinal epithelium,caused a more severe loss of dopaminergic neurons in the substantia nigra following MPTP challenge,and this was accompanied by a reduced abundance of succinate-producing Alleoprevotella in the gut microbiota.Administration of succinate markedly attenuated dopaminergic neuronal loss in MPTP-treated mice by elevating the mitochondrial membrane potential.This study suggests that intestinal epithelial DRD2 activity and succinate from the gut microbiome contribute to the maintenance of nigral DA neuron survival.These findings provide a potential strategy targeting neuroinflammation-related neurological disorders such as PD.