Autophagy protects neurons against facial nerve injury in rats

doi:10.12307/2024.508

Abstract

Abstract: BACKGROUND: After peripheral facial nerve injury, glial cell-derived neurotrophic factor (GDNF) can play a protective role in facial neurons. It has been found that GDNF can regulate the level of autophagy through mammalian target of rapamycin (mTOR), but it is unclear whether it can regulate facial neurons through the adenylate-activated protein kinase/Unc-51-like kinase 1 (AMPK/ULK1) signaling pathway after facial nerve injury.
OBJECTIVE: To establish a facial nerve injury model in Sprague-Dawley rats and explore the role of autophagy in facial nerve regeneration and the mechanism by which the GDNF/AMPK/ULK1 signaling pathway promotes facial nerve repair after injury.
METHODS: Seventy-two Sprague-Dawley rats were randomly divided into sham group, model group and autophagy inhibitor 3-methyladenine (3-MA) group, with 24 rats in each group. Only the main trunk of the facial nerve was exposed in the sham group, while the remaining two groups were modeled for the compression injury of the facial nerve trunk. After successful modeling, the model group was given intraperitoneal injection of normal saline (15 mg/kg), and the 3-MA group was given intraperitoneal injection of 3-MA (15 mg/kg), both once daily for 7 days. The rats in each group were scored on the Simone 10-point behavioral scale at 1, 4, 7, 14, 21 and 28 days after surgery. Nissl staining was performed to observe the morphology and number of facial neuron cells at 7, 14, 21, and 28 days. The expression levels of p-AMPK, p-ULK1, Beclin1 and GDNF in the facial neuron tissues of rats were detected by western blot assay.
RESULTS AND CONCLUSION: Behavioral scoring showed that the improvement of facial paralysis symptoms in the 3-MA group was worse and later than that in the model group (P < 0.05). Nissl staining showed that the morphology and number of Nissl bodies in facial neurons in the 3-MA group recovered poorly and the number was less than that in the model group (P < 0.05). Western blot detection results showed that the expression of p-AMPK and Beclin1 in the model group was higher than that in the 3-MA group and the sham group (P < 0.05). The protein expression of p-ULK1 in the model group was lower than that in the 3-MA group and the sham group (P < 0.05). To conclude, autophagy inhibitor delays nerve repair after facial nerve injury, which may be related to down-regulation of GDNF expression, inactivation of AMPK, and phosphorylation of ULK1, thereby inhibiting neuronal autophagy levels.

Key words: facial nerve injury, peripheral facial paralysis, autophagy, facial neuron, glial cell-derived neurotrophic factor, AMPK, ULK1, Beclin1, Nissl body

CLC Number:

Duan Kunling, Fei Jing, Li Leiji. Autophagy protects neurons against facial nerve injury in rats[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(27): 4378-4382.

Figures/Tables 3

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