Ameliorative Role of Mitochondrial Therapy in Cognitive Function of Vascular Dementia Mice

Article type: Research Article

Authors: Wu, Deng-Pan^{a; b; 1} | Wei, Yan-Su^{a; 1} | Du, Yu-Xuan^{a; 1} | Liu, Ling-Ling^a | Yan, Qiu-Qing^a | Zhao, Yuan-Dan^a | Yu, Chao^c | Liu, Jin-Yuan^a | Zhong, Zhen-Guo^d | Huang, Jin-Lan^{a; b; *}

Affiliations: [a] Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Pharmacy School, Xuzhou Medical University, Xuzhou, Jiangsu, China | [b] Xuzhou Ruihu Health Management Consulting Co., Ltd, Xuzhou, Jiangsu, China | [c] School of Basic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China | [d] Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, China

Correspondence: [*] Jin-Lan Huang, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Pharmacy School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.Tel.: +86051683262107; E-mail: [email protected].

Note: [1] These authors contributed equally to this project.

Abstract: Background:Mitochondrial dysfunction plays a vital role in the progression of vascular dementia (VaD). We hypothesized that transfer of exogenous mitochondria might be a beneficial strategy for VaD treatment. Objective:The study was aimed to investigate the role of mitochondrial therapy in cognitive function of VaD. Methods:The activity and integrity of isolated mitochondria were detected using MitoTracker and Janus Green B staining assays. After VaD mice were intravenously injected with exogenous mitochondria, Morris water maze and passive avoidance tests were used to detect cognitive function of VaD mice. Haematoxylin and eosin, Nissl, TUNEL, and Golgi staining assays were utilized to measure neuronal and synaptic injury in the hippocampus of VaD mice. Detection kits were performed to detect mitochondrial membrane potential (ΔΨ), SOD activity and the levels of ATP, ROS, and MDA in the brains of VaD mice. Results:The results showed that isolated mitochondria were intact and active. Mitochondrial therapy could ameliorate cognitive performance of VaD mice. Additionally, mitochondrial administration could attenuate hippocampal neuronal and synaptic injury, improve mitochondrial ΔΨ, ATP level and SOD activity, and reduce ROS and MDA levels in the brains of VaD mice. Conclusions:The study reports profitable effect of mitochondrial therapy against cognitive impairment of VaD, making mitochondrial treatment become a promising therapeutic strategy for VaD.

Keywords: Alzheimer’s disease, cognitive function, dementia, mitochondrial therapy, oxidative stress, vascular dementia

DOI: 10.3233/JAD-230293

Journal: Journal of Alzheimer's Disease, vol. 97, no. 3, pp. 1381-1392, 2024