Evidence Details for Ulk1
PMID Title Journal Year Abstract
36422883 Acupuncture promotes nerve repair through the benign regulation of mTOR-mediated neuronal autophagy in traumatic brain injury rats. CNS Neurosci Ther. 2023 Jan;29(1):458-470. doi: 10.1111/cns.14018. Epub 2022 Nov 24. 2023 Jan AIMS: Recent investigations have already proved the neuroprotective efficacy of acupuncture in clinical practice in the treatment of neurological diseases, such as traumatic brain injury (TBI). Since growing evidence has suggested that neuronal autophagy was involved in multiple stages of TBI, this study aims to clarify the autophagy mediating mechanism underlying the neuroprotective effect of acupuncture in TBI rats. METHODS: Three experiments were carried out to detect changes in neuronal autophagy and identify the potential molecular mechanism underlying the neuroprotective effect of acupuncture for TBI treatment. Feeney's free-falling epidural impingement method was used to establish the moderate TBI rat model; modified neurological severity scoring (mNSS) was used for neurological recovery evaluation. Nissl and HE staining were used to examine the histopathological changes. Immunofluorescence was used to detect the LC3-positive cell rate. The transmission electron microscope (TEM) was used to investigate the morphology and quantity of autophagosomes. Western blotting was used to determine the protein expressions of LC3, p62, beclin1, mTOR, ULK1, p-mTOR, and p-ULK1. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for gene expressions analysis of LC3 mRNA and p62 mRNA. Co-immunoprecipitation (CO-IP) method was used to identify the protein interaction of mTOR and ULK1. RESULTS: On Day 3 after TBI, acupuncture accelerated the removal of damaged cellular structures by promoting neuronal autophagy; on Day 7 and Day 14 after TBI, acupuncture inhibited neuronal autophagy, preventing excessive autophagy and thus alleviated nerve damage. In addition, the simultaneous treatment with 3-MA or rapamycin at different stages after TBI attenuated the effect of acupuncture. CONCLUSION: Acupuncture has a benign regulatory effect on neuronal autophagy in different stages of TBI, possibly through the mTOR/ULK1 pathway."

Evidence Sentence: Acupuncture has a benign regulatory effect on neuronal autophagy in different stages of TBI, possibly through the mTOR/ULK1 pathway.
Evidence Sentence: Collectively, acupuncture may mediate the autophagy of cerebral cortex neurons through the mTOR/ULK1 pathway, thus exhibiting a neuroprotective effect.
Evidence Sentence: To further explore its molecular mechanism, we detected protein levels of p-mTOR, mTOR, p-UlK1Ser757, and ULK1 with Western blotting.
Evidence Sentence: As illustrated in Figure 5F and Figure 5G, acupuncture enhanced the p-mTOR /mTOR ratio and p-ULK1Ser757 /ULK1 ratio on Day 7 after TBI.
Evidence Sentence: Moreover, the CO-IP results (Figure 5H) showed that acupuncture treatment accelerated the connection between mTOR and ULK1, while the connection was inhibited under rapamycin combination therapy.
Evidence Sentence: Western blotting was used to determine the protein expressions of LC3, p62, beclin1, mTOR, ULK1, p-mTOR, and p-ULK1.
Evidence Sentence: Co-immunoprecipitation (CO-IP) method was used to identify the protein interaction of mTOR and ULK1.
Evidence Sentence: In the injured cortex, the expression levels of p-mTOR/mTOR (Figure 3A and Figure 3B) and p-ULK1Ser757 /ULK1 (Figure 3A,C) in TBI rats increased, but decreased significantly after acupuncture treatment on Day 3 after TBI.
Evidence Sentence: Acupuncture accelerated the expression of p-mTOR /mTOR and p-ULK1ser757/ULK1 on Day 7 and Day 14 in TBI rats.
Evidence Sentence: Of note, 3-MA abrogated the acupuncture-mediated decrease in the p-mTOR/mTOR ratio and p-ULK1Ser757/ULK1 ratio.
Evidence Sentence: CO-IP results (Figure 4G) showed that 3-MA also enhanced the acupuncture-mediated weakening of the mTOR and ULK1 connection.