Neuroprotective role and mechanism of S14G-humanin in amyloid precursor protein/presenolin-1 double transgenic mice / 中华神经医学杂志

ABSTRACT

Objective:To investigate the effect of S14G-humanin (HNG) on spatial learning and memory abilities and hippocampal neuron autophagy in amyloid precursor protein (APP)/presenolin-1 (PS1) double-transgenic mice.Methods:The APP/PSl transgenic mice were randomly divided into model group and HNG treatment group ( n=8). Another 8 C57BL/6J mice were chosen as controls; 0.5 mL double-steamed water was intraperitoneally injected into mice in the control group and model group every day, and 0.5 mL of HNG (50 μg/kg) was intraperitoneally injected into mice in the HNG treatment group every day; after 4 weeks of continuous injection, Morris water maze test was used to test the spatial learning and memory abilities of mice in each group. Western blotting and reverse transcription-PCR were used to detect the protein and mRNA expressions of ubiquitin like kinase1 (ULK1), P62, anti-microtubule associated protein 1 light chain 3 (LC3) II/LC3 I and cathepsin D in the hippocampus. Immunohistochemical staining was used to detect the deposition of amyloid β protein (Aβ) in the hippocampus of mice in each group. Results:Morris water maze test showed that the escape latency of mice in the control group, HNG treatment group and model group was statistically prolonged in turn, and the number of times traversing through the quadrant of the original platform was significantly smaller in turn ( P<0.05). Western blotting and reverse transcription-PCR showed that the ULK1 protein and mRNA expressions in the hippocampus decreased successively, P62 protein and mRNA expressions increased successively, LC3 II protein/LC3 I protein and LC3 II mRNA/ LC3 I mRNA ratio increased successively, and cathepsin D protein and mRNA expressions decreased successively in the control group, HNG treatment group and model group, with significant differences ( P<0.05). Immunohistochemical staining showed that the Aβ positive expressions in the hippocampal neurons of the control group, HNG treatment group and model group increased successively, with statistical differences ( P<0.05). Conclusion:HNG treatment can improve the spatial learning and memory abilities, which may be attributed to ameliorate autophagic network dysfunction and reduce Aβ plaques in the hippocampi of APP/PSl transgenic mice.