Effect of TGF-β1 on intermittent hypoxia induced autophagy in hippocampal neurons

Abstract

Objective To investigate the effect of TGF-β1 on autophagy in hippocampal neurons induced by intermittent hypoxia. Methods In vivo experiment: Twelve SD rats were randomly divided as control group (N group) and intermittent hypoxia group (IH group); Their cognitive function was assessed by Morris water maze; Neuronal autophagy was observed by transmission electron microscopy and immunohistochemical assay; The expression of LC3, P62 and TGF-β1 in the hippocampus was detected by Western blotting. In vitro experiment: the mouse hippocampal neuron cell line (HT22 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. Results Compared with the N group, the average escape latency and the residence time in the target quadrant were both prolonged in the IH group (P < 0.05). Besides, the number of autophagosomes was increased under electron microscope and the stained intensity of LC3 was enhanced in immunohistochemical assay. Western blotting indicated that the expression of LC3-Ⅱ/LC3-Ⅰ and P62 was up-regulated (P < 0.05), while that of TGF-β1 was down-regulated (P < 0.05) in the in vitro and in vivo experiments. Compared with the IH group, the protein level of TGF-β1 was up-regulated, while that of LC3-Ⅱ/LC3-Ⅰ and P62 was decreased (P < 0.05) in the IH+TGF-β1 group (P < 0.05); The expression of LC3-Ⅱ/LC3-Ⅰ was increased in the IH+SB431542 group (P < 0.05). Conclusion Intermittent hypoxia causes cognitive dysfunction in rats, which is probably related to the accumulation of neuronal autophagy. TGF-β1 attenuates the increase of neuronal autophagy induced by intermittent hypoxia.

Keywords

• intermittent hypoxia
• transforming growth factor-β1
• neurous autophagy
• cognitive impairment