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Biochem Biophys Res Commun. 2018 Jul 2;501(4):1016-1022. doi: 10.1016/j.bbrc.2018.05.101. Epub 2018 May 18.

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

Author information

1
The First Clinic Medical College, College of Medicine, Nanchang University, Nanchang, Jiangxi, China.
2
Queen Mary Institute, School of Medicine, Nanchang University, Nanchang, Jiangxi, 330006, China.
3
Department of Respiration, College of Medicine, Nanchang University, Nanchang, Jiangxi, China; Department of Respiration, Department Two, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China. Electronic address: fuqiangfqa@sohu.com.
4
Department of Pathophysiology, College of Medicine, Nanchang University, Nanchang, Jiangxi, China; Institute of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, 33006, China. Electronic address: zhenzhenhuzzh@126.com.

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 and caspase-3 levels and increased Bcl-2 level in rat hippocampus. Our results therefore indicate that CART peptide could serve as an antioxidant in early therapy for AD.

KEYWORDS:

Alzheimer's disease (AD); Amyloid-beta (Aβ); Antioxidant; CART peptide; Nrf2; Oxidative stress

PMID:
29777699
DOI:
10.1016/j.bbrc.2018.05.101
[Indexed for MEDLINE]

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