Kailin Yin1, Jiali Jin1, Xiaolei Zhu1, Linjie Yu1, Sulei Wang2, Lai Qian1, Lijuan Han1, Yun Xu1,2. 1. a Department of Neurology , Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China. 2. b Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing , China.
Abstract
INTRODUCTION: Cocaine- and amphetamine-regulated transcript (CART) peptide has been demonstrated to exert neuroprotective effects in stroke and some neurodegeneration diseases. In current study, we investigated the protective effects and underlying mechanisms of CART in APP/PS1 mice. METHODS: The protein levels of CART, soluble Aβ1-40 and Aβ1-42 were measured in the hippocampus of APP/PS1 mice by enzyme-linked immunosorbent assay. We determined the mRNA and protein levels of Aβ metabolism-associated enzymes including neprilysin (NEP), insulin-degrading enzyme (IDE), receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP-1) in the hippocampus of APP/PS1 mice using real-time PCR and western blotting. Spatial memory was measured in APP/PS1 mice using the Morris water maze. The phosphorylation of AKT, ERK, p38, and JNK was determined using western blotting. RESULTS: The levels of soluble Aβ1-40 and Aβ1-42 were significantly decreased in the hippocampus of APP/PS1 mice after CART treatment. CART modulated the levels of NEP, IDE, RAGE, and LRP-1. In addition, CART inhibited the MAPK pathways and activated the AKT pathway, whereas inhibition of the AKT pathway decreased the levels of IDE and LRP-1. Furthermore, CART attenuated spatial memory deficits in the APP/PS1 mice. CONCLUSION: CART decreases the levels of soluble Aβ in the hippocampus of APP/PS1 mice by modulating the expression of Aβ metabolism-associated enzymes, which may be associated with the MAPK and AKT pathways.
INTRODUCTION:Cocaine- and amphetamine-regulated transcript (CART) peptide has been demonstrated to exert neuroprotective effects in stroke and some neurodegeneration diseases. In current study, we investigated the protective effects and underlying mechanisms of CART in APP/PS1mice. METHODS: The protein levels of CART, soluble Aβ1-40 and Aβ1-42 were measured in the hippocampus of APP/PS1mice by enzyme-linked immunosorbent assay. We determined the mRNA and protein levels of Aβ metabolism-associated enzymes including neprilysin (NEP), insulin-degrading enzyme (IDE), receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP-1) in the hippocampus of APP/PS1mice using real-time PCR and western blotting. Spatial memory was measured in APP/PS1mice using the Morris water maze. The phosphorylation of AKT, ERK, p38, and JNK was determined using western blotting. RESULTS: The levels of soluble Aβ1-40 and Aβ1-42 were significantly decreased in the hippocampus of APP/PS1mice after CART treatment. CART modulated the levels of NEP, IDE, RAGE, and LRP-1. In addition, CART inhibited the MAPK pathways and activated the AKT pathway, whereas inhibition of the AKT pathway decreased the levels of IDE and LRP-1. Furthermore, CART attenuated spatial memory deficits in the APP/PS1mice. CONCLUSION:CART decreases the levels of soluble Aβ in the hippocampus of APP/PS1mice by modulating the expression of Aβ metabolism-associated enzymes, which may be associated with the MAPK and AKT pathways.