The Role Of TGF-β1 In Cognitive Dysfunction Induced By Intermittent Hypoxia In Rats

ObjectionThe experiment established intermittent hypoxia rats and HT22 cell models to explore the role and mechanism of TGF-β1 in intermittent hypoxia-induced cognitive dysfunction in rats.MethodsIn vivo experiment:Twelve SD rats were divided into non-treated group(N group)and intermittent hypoxia group(IH group).Behavioral testing(Morris Water Maze)aimed to observe cognitive deficits;Transmission electron microscopy and immunohistochemistry were used to observe Neuronal autophagy changes;the different protein expression(LC3,P62 and TGF-β1)was obtained/detected by Western blot.In vitro experiment:the mouse hippocampal neuron cell line(HT-22 cells)was divided as control group(N group),intermittent hypoxia group(IH group),intermittent hypoxia+TGF-β1 group(IH+TGF-β1 group)and intermittent hypoxia+SB431542 group(IH+SB431542 group),the expression of TGF-β1,LC3 and P62 was detected by Western blotting.ResultsCompared with N group,the average escape latency and the residence time in the target quadrant were both prolonged(P<0.05)in IH group.Besides,the number of Autophagosomes increased under electron microscope and LC3 staining enhanced by immunohistochemical.By means of western blot,the expression of LC3-II/LC3-I and P62 were up-regulated(P<0.05),while the expression of TGF-β1 was down-regulated(P<0.05)in vitro and in vivo Experiments.In comparison with IH group,at the protein level,TGF-β1 increased,while LC3-II/LC3-I and P62 decreased(P<0.05)in IH+TGF-β1 group(P<0.05);LC3-II/LC3-I increased in IH+SB431542 group(P<0.05).ConclusionsIntermittent hypoxia causes cognitive dysfunction in rats,which is probably related to the accumulation of neuronal autophagy.TGF-β1 reduces the increase of neuronal autophagy induced by intermittent hypoxia.