The Effect of Hippocampal Cognitive Impairment and XIAP on Glucose and Lipids Metabolism in Rats

Abstract

Background/Aims: To investigate the effect of cognitive impairment and X-linked inhibitor of apoptosis protein (XIAP) on glucolipid metabolism. Materials and Methods: β-amyloid (Aβ 1-42) was injected into the hippocampus of rats to establish a cognitive impairment model. Trans-activator of transcription (TAT)-XIAP fusion protein (the TAT-XIAP group), PBS (the model group), or XIAP antisense oligonucleotides (the ASODN group) was injected into the lateral ventricles of the rats to increase and decrease the activity of XIAP in the hippocampus. To determine the level of blood glucose and lipids, adenosine monophosphate-activated protein kinase (AMPK) expression of liver and hipppocamual neuronal apoptosis. Results: The levels of FPG, TG, TC and LDL were significantly higher in the TAT-XIAP group, the model group and the ASODN group than in the blank group (P < 0.05); however, the HDL level showed no significant change in all groups of rats. The apoptosis indexes of the rat hippocampal CA1 neuron were 68.44 ± 4.31%, 13.21 ± 2.30%, 56.68 ± 4.771%, and 87.51 ± 6.63% in the model group, the blank group, the TAT-XIAP group and the ASODN group, respectively. Gastrointestinal motility was less frequent (per time unit) in the model group, the ASODN group and the TAT-XIAP group than in the blank group. Compared with the model group, gastrointestinal motility was significantly less frequent in the ASODN group and was significantly more frequent in the TAT-XIAP group. Compared with the blank group, the model group had a significantly lower gastric emptying rate and intestinal propulsive rate. Compared with the model group, the gastric emptying rate and intestinal propulsive rate were significantly lower in the ASODN group and were significantly higher in the TAT-XIAP group. Compared with the blank group, the expressions of AMPK mRNA, and AMPK protein were significantly reduced in the model group, the TAT-XIAP group, and the ASODN group. AMPK expression was significantly increased in the TAT-XIAP group and was significantly decreased in the ASODN group than in the model group. Conclusion: Cognitive impairment and hippocampal neuron apoptosis can cause glucose and lipids metabolic abnormalities, possibly by regulating gastrointestinal motility and AMPK expression in the liver. The changes in the function of XIAP, which is an anti-apoptotic protein in the hippocampus, may affect the metabolism of glucose and lipids.