Blocking retrograde axonal transport of autophagosomes contributes to sevoflurane-induced neuron apoptosis in APP/PS1 mice

AbstractAutophagy, a crucial pathway for the degradation of proteins in eukaryotic cells, is linked to the development of Alzheimer ’s disease (AD), and the accumulated autophagosomes in the cells resulting in the death of cells. Sevoflurane can impair spatial learning and memory in mice with AD and lead to the apoptosis of nerve cells; however, the underlying mechanisms remain unknown. We aim to explore the effects and underl ying mechanisms of sevoflurane in APPswe/PS1ΔE9 double-transgenic mice. 51 heterozygous APPswe/PS1ΔE9 double-transgenic mice were involved and divided into three groups, including control group, sham group and sevoflurane group. Morris water maze experiment was used to test the learning and memory abilities of mice, flow cytometry was conducted to detect apoptosis and mitochondrial membrane potential of brain cells in mice, transmission electron microscopy was used to observe the number of autophagosomes at the axon in mice, and western blot was carried out to detect the expression of Bax, B cl-2, LC3II, P62, KIF3B and DIC proteins of brain cells in mice. In our study, we found that significantly longer escape latencies, fewer crossings of the platform and shorter time spent in the target quadrant of the morris water maze experiment in the sevoflurane group. Flow cytometry showed cellul ar apoptosis was increased and the membrane potential of the mitochondria was reduced of brain cells in the sevoflurane group. Transmission electron microscopy displ...
Source: Acta Neurologica Belgica - Category: Neurology Source Type: research