<p>Metformin Inhibits Propofol-Induced Apoptosis of Mouse Hippocampal Neurons HT-22 Through Downregulating Cav-1</p>

Abstract

To elucidate the neuroprotective function of metformin in suppressing propofolinduced apoptosis of HT-22 cells. Methods: HT-22 cells were treated with 0, 10 or 100 μmol/L propofol, followed by determination of their proliferative ability. Subsequently, changes in proliferation and apoptosis of propofol-treated HT-22 cells induced with metformin were assessed. Apoptosisassociated genes in HT-22 cells were detected by Western blot. At last, regulatory effects of Cav-1 on propofol and metformin-treated HT-22 cells were examined. Results: Propofol treatment dose-dependently decreased proliferative ability and increased apoptosis ability in HT-22 cells, which were partially blocked by metformin administration. Upregulated Bcl-2 and downregulated Bax were observed in propofol-treated HT-22 cells following metformin administration. In addition, Cav-1 level in HT-22 cells was regulated by metformin treatment. Notably, metformin reversed propofol-induced apoptosis stimulation and proliferation decline in HT-22 cells via downregulating Cav-1. Conclusion: In our study, we found that propofol could induce apoptosis of HT-22 cells and metformin could rescue the apoptosis effect regulated by propofol. Then, we found that metformin protects propofol-induced neuronal apoptosis via downregulating Cav-1.

Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study

“…However, they had no impact on cell viability at medium concentrations and were cytotoxic at higher concentrations (more than 50 µM) and more prolonged treatments (more than 24 h), particularly for perampanel. Although not as efficient as edaravone, metformin and perampanel also can increase cell viability, which is in line with data from previous studies [ 30 , 31 ]. Although these effects of perampanel were particularly obvious when using the MTT assay, which we have demonstrated to be more precise and sensitive to small changes in both cell lines, they were similar to those obtained with the other viability assays used in the present study.…”

Effects of Dexmedetomidine on the Expression of Cytochrome C Oxidase in Neonatal Mouse Primary Hippocampal Neurons Cultured in Propofol

“…Therefore, this study selected the hippocampal neurons of neonatal mice within 1 d of birth as the research object. Referring to the methods described by Ge et al [6] and Lv et al [7] , in this study hippocampal neurons were incubated with 20 μM propofol to induce neuronal damage and the final concentration of dexmedetomidine was set to 10 μM. The results of this study suggest that compared with those in the control group, the primary hippocampal neurons in the propofol group had an abnormal morphology, with shortened neurites and sparse axons and dendrites.…”

“…The medium was replaced with prewarmed neurobasal medium containing B27 and half the medium was changed every 3 d. The growth of neurons was observed under a microscope. Cultured primary hippocampal neurons were treated with different concentrations of propofol and dexmedetomidine based on the experimental groupings [6,7] ; control group (0 μM propofol and 0 μM dexmedetomidine); propofol group (20 μM propofol and 0 μM dexmedetomidine) and propofol+dexmedetomidine group (20 μM propofol and 10 μM dexmedetomidine). All cells were incubated for 1 h. After centrifuging the cell suspension, the supernatant was discarded and the cells were washed 2-3 times with Phosphate-Buffered Saline (PBS).…”

Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders

“…In neurons with persistent prion infection, metformin significantly reduced cellular prion protein load and inhibited prion transforming activity, which may be explained by higher levels of autophagy [ 130 ]. Metformin improved propofol-induced HT-22 cell apoptosis and downregulated caveolin-1, a class of membrane proteins involved in the activation of autophagy [ 131 ]. Metformin reduced the abnormal HD protein load and fully restored the early network activity patterns characterized by increased activity, enhanced synchronicity, and hyperactive neurons [ 21 ].…”