Relationship between mechanical ventilation-induced apoptosis in hippocampal neurons and mTOR signaling pathway in mice

Abstract

Objective To evaluate the relationship between mechanical ventilation-induced apoptosis in hippocampal neurons and mammalian taget of rapamycin(mTOR)signaling pathway in mice. Methods Fifty healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 2 groups (n=25 each) using a random number table method: control group (group C) and mechanical ventilation group (group V). The mice breathed spontaneously for 6 h in group C, and the mice were mechanically ventilated for 6 h in group V. Open field test and contextual fear conditioning test were conducted at 1 and 3 days after the end of ventilation.Hippocampal tissues were obtained at 1 day after the end of ventilation for determination of the expression of mTOR, phosphorylated mTOR (p-mTOR), microtubule-associated protein 1 light chain 3 Ⅱ(by Western blot)and apoptosis in hippocampal neurons (by TUNEL). The p-mTOR/mTOR ratio and apoptosis index were calculated. Results Compared with group C, the time animals spent in the central square was significantly prolonged, the number of crossing the grid was reduced, the percentage of freezing time was decreased, the expression of microtubule-associated protein 1 light chain 3 Ⅱ was up-regulated, and the p-mTOR/mTOR ratio and apoptosis index were increased in group V (P<0.05). Conclusion The mechanism by which mechanical ventilation induces apoptosis in hippocampal neurons may be related to activation of mTOR signaling pathway in mice. Key words: Respiration, artificial; Apoptosis; Receptor-interacting protein serine-threonine kinases; Cognition disorders