CART peptide activates the Nrf2/HO-1 antioxidant pathway and protects hippocampal neurons in a rat model of Alzheimer's disease

Biochemical and Biophysical Research Communications
Wenyu JiaoZhenzhen Hu

Abstract

The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ1-42 (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0.02μg/hemisphere) into rat hippocampus was administered for five consecutive days before Aβ1-42 treatment. We found that Aβ1-42 microinjection led to reduction of endogenous CART level in rat hippocampus. CART pretreatment improved the spatial memory and locomotor ability of AD rats. CART peptide decreased the Aβ1-42 and Aβ production-associated enzyme BACE1 levels. Moreover, CART peptide attenuated the oxidative stress damage with a concrete manifestation of increased MDA as well as decreased T-SOD, GSH and ATP levels in the hippocampus of Aβ1-42-treated rat, which may be causatively implicated the activating of Nrf2/HO-1 signaling pathway. Furthermore, CART peptide attenuated neuronal apoptosis with decreased Bax, caspase-9 ...Continue Reading

Citations

Jan 9, 2019·Neuromolecular Medicine·Gahee Bahn, Dong-Gyu Jo
Jun 13, 2019·Journal of Cellular and Molecular Medicine·Ruhui YangSongquan Wu
Mar 3, 2020·Phytotherapy Research : PTR·Cong LuFengzhong Wang
Oct 6, 2020·Journal of Alzheimer's Disease : JAD·Zizhen Si, Xidi Wang
Aug 4, 2018·International Journal of Molecular Sciences·Mariapaola NittiAnna Lisa Furfaro
Aug 29, 2019·Current Alzheimer Research·Carla PetrellaCinzia Severini
Aug 28, 2019·Open Life Sciences·Lihua LiXiangrong Tian
Apr 18, 2021·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Bei ZhangGang Li
Aug 28, 2021·Cells·Don A DaviesBenedict C Albensi

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