CART mitigates oxidative stress and DNA damage in memory deficits of APP/PS1 mice via upregulating β‑amyloid metabolism‑associated enzymes

Jiang,Hui; Niu,Fengnan; Zheng,Yan; Xu,Yun

doi:10.3892/mmr.2021.11919

CART mitigates oxidative stress and DNA damage in memory deficits of APP/PS1 mice via upregulating β‑amyloid metabolism‑associated enzymes

Authors:
- Hui Jiang
- Fengnan Niu
- Yan Zheng
- Yun Xu
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Affiliations: Department of Neurology, Affiliated Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China, Departnment of Neurology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
Published online on: February 17, 2021 https://doi.org/10.3892/mmr.2021.11919
Article Number: 280
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

Alzheimer's disease (AD) is the most common form of dementia that is primarily characterized by progressive cognitive deficits. The toxicity of amyloid β‑protein (Aβ) serves an important role in the progression of AD, resulting in neuronal loss via a number of possible mechanisms, including oxidative stress, mitochondrial dysfunction, energy depletion, apoptosis and neuroinflammation. Previous studies have reported that cocaine amphetamine regulated transcript (CART) treatment improves memory and synaptic structure in APP/PS1 mice. Therefore, the present study aimed to investigate whether CART served a protective role against memory deficits in AD. APP/PS1 mice were treated with CART or PBS. Spatial memory was assessed using the Morris water maze. Oxidative stress and DNA damage were compared among wild‑type, APP/PS1 and CART‑treated APP/PS1 mice. The mRNA and protein expression 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 were measured via reverse transcription‑quantitative PCR and western blotting, respectively. CART improved the memory impairment of APP/PS1 mice by reducing oxidative stress, inhibiting DNA damage and protecting against mitochondrial dysfunction in the cerebral cortex and hippocampus. CART also reduced cell senescence and oxidative stress in Aβ1‑42‑exposed primary cortical neurons in APP/PS1 mice. Moreover, CART promoted Aβ degradation via modulating Aβ metabolism‑associated enzymes, including IDE, NEP, LRP‑1 and RAGE. Collectively, the present study indicated that CART improved the learning and memory capacity of APP/PS mice, thus may have potential to serve as a novel therapeutic agent for AD.

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