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The role of mTOR signaling pathway on cognitive functions in cerebral ischemia-reperfusion
Liying Yang1, Yingying Zhang1, Zhongrui Yan2
1Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Abstract:
The role and mechanism of the mTOR signaling pathway in the impaired cognitive function in cerebral ischemia-reperfusion were examined in the present study. Sprague-Dawley (SD) rats were divided into the sham operation, cerebral ischemia, cerebral ischemia-reperfusion and cerebral ischemia-reperfusion adaptive groups. A Morris water maze test was carried out in the different treatment groups at 2 weeks after surgery to detect cognitive function. After the experimental animals were sacrificed, fluorescent quantitative PCR test was used to detect the key signaling molecules in the mTOR signaling pathway in the different treatment groups, such as mTOR, p-mTOR, AKT and p-AKT gene mRNA expression. The protein expression was determined by enzyme-linked immunosorbent assay and western blotting. mTOR expression and localization in the different treatment groups was detected by immunohistochemistry, and the positive cell rate was determined. Compared with the sham operation group, the levels of mTOR, p-mTOR, AKT and p-AKT mRNAs and hippocampal proteins were significantly lower in the cerebral ischemia group and cerebral ischemia-reperfusion group (P<0.05). Levels of mTOR, p-mTOR, AKT and p-AKT mRNAs and proteins in the cerebral ischemia-reperfusion adaptive group decreased but did not show significant differences (P>0.05). The Morris water maze results showed that, the adaptive ability and the cognitive functions were improved significantly in the cerebral ischemia-reperfusion adaptive group when compared with the cerebral ischemia and cerebral ischemia-reperfusion groups (P<0.05). The number of mTOR-positive cells in hippocampus was significantly higher in the sham operation and cerebral ischemia-reperfusion adaptive groups, but there was no difference between these groups. In conclusion, mTOR signaling pathway improves the cognitive function in cerebral ischemia-reperfusion in rats.
Insights
The mechanistic target of rapamycin (mTOR) signaling pathway enhances cognitive function recovery after cerebral ischemia-reperfusion in rats. This study investigated mTOR
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Cerebral ischemia-reperfusion (CIR) injury impairs cognitive function.
- The mechanistic target of rapamycin (mTOR) signaling pathway is implicated in cellular processes relevant to brain injury and recovery.
Purpose of the Study:
- To investigate the role and mechanism of the mTOR signaling pathway in cognitive dysfunction following CIR in rats.
- To assess the impact of CIR and adaptive interventions on mTOR pathway activity and cognitive performance.
Main Methods:
- Establishment of sham operation, CIR, and CIR adaptive rat models.
- Assessment of cognitive function using the Morris water maze test.
- Quantification of mTOR, p-mTOR, AKT, and p-AKT gene mRNA and protein expression via qRT-PCR, ELISA, and Western blotting.
- Immunohistochemical analysis of mTOR expression and localization in the hippocampus.
Main Results:
- CIR significantly reduced mTOR, p-mTOR, AKT, and p-AKT mRNA and protein levels in the hippocampus.
- Cognitive function and adaptive ability were significantly improved in the CIR adaptive group compared to CIR groups.
- mTOR expression in the hippocampus was upregulated in the sham and CIR adaptive groups.
Conclusions:
- The mTOR signaling pathway plays a crucial role in improving cognitive function after cerebral ischemia-reperfusion in rats.
- Targeting the mTOR pathway may offer therapeutic potential for mitigating cognitive deficits associated with CIR.
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