机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Changchun Street 45, Xicheng District, Beijing, China神经科系统神经内科首都医科大学宣武医院[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[4]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, People’s Republic of China
Mitochondrial dysfunction plays a fundamental role in the pathogenesis of cognitive deficit. Rutaecarpine (Rut) is a natural alkaloid with anti-inflammatory and antioxidant properties. This study explored whether Rut treatment could enhance cognitive function by improving mitochondrial function and examined the potential mechanisms underlying this ameliorative effect. We used the Morris water maze and Y-maze tests to evaluate the behavioral effects of Rut in a mouse model of cognitive impairment induced by subcutaneous injection of D-galactose (D-gal). Furthermore, we assessed the effects of Rut on mitochondrial function using cell viability assays, flow cytometry, western blotting, biochemical analysis, and immunochemical techniques in vivo and in vitro. The results indicated Rut treatment attenuated cognitive deficits and mitochondrial dysfunction in the mouse model. Similarly, it maintained the balance of mitochondrial dynamics in neurocytes and reduced oxidative stress and mitochondrial apoptosis in the HT22 cell model. Moreover, we found that these protective effects were dependent on the activation of the AMP-activated protein kinase/proliferator-activated receptor gamma coactivator 1-alpha (AMPK/PGC1 & alpha;) signaling pathway. Our data indicate that Rut treatment are sensitive to reversal cognitive deficits and mitochondrial dysfunction induced by D-gal; this suggests that Rut is a promising mitochondria-targeted therapeutic agent for treating cognitive impairment.
基金：
This study was supported by the Key Project of the National
Natural Science Foundation of China (U20A20354), Beijing Brain
Initiative from Beijing Municipal Science & Technology Commission
(Z201100005520016, Z201100005520017), National major
R&D projects of China-Scientific technological innovation 2030
(2021ZD0201802), the National Key Scientific Instrument and Equipment
Development Project (31627803), and the Key Project of the
National Natural Science Foundation of China (81530036).
第一作者机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Changchun Street 45, Xicheng District, Beijing, China
通讯作者：
通讯机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Changchun Street 45, Xicheng District, Beijing, China[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[4]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, People’s Republic of China
推荐引用方式(GB/T 7714)：
Gong Min,Jia Jianping.Rutaecarpine Mitigates Cognitive Impairment by Balancing Mitochondrial Function Through Activation of the AMPK/PGC1 & alpha; Pathway[J].MOLECULAR NEUROBIOLOGY.2023,60(11):6598-6612.doi:10.1007/s12035-023-03505-6.
APA：
Gong, Min&Jia, Jianping.(2023).Rutaecarpine Mitigates Cognitive Impairment by Balancing Mitochondrial Function Through Activation of the AMPK/PGC1 & alpha; Pathway.MOLECULAR NEUROBIOLOGY,60,(11)
MLA：
Gong, Min,et al."Rutaecarpine Mitigates Cognitive Impairment by Balancing Mitochondrial Function Through Activation of the AMPK/PGC1 & alpha; Pathway".MOLECULAR NEUROBIOLOGY 60..11(2023):6598-6612
