Nicotine Modulates Cognitive Function in D-Galactose-Induced Senescence in Mice

Frontiers in Aging Neuroscience

Albert Gjedde³  Fereshteh Farajdokht⁵  Saeed Sadigh-Eteghad⁵  Alireza Majdi⁵  Mahnaz Talebi⁵  Marjan Erfani⁵  Javad Mahmoudi⁵ 

[1]Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada

[2]Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark

[3]Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States

[4]Departments of Clinical Research and Nuclear Medicine, Odense University Hospital, University of Southern Denmark, Odense, Denmark

[5]Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

关键词: aging;    nicotine;    learning and memory;    oxidative stress;    mitochondrial dysfunction;    neurotrophic factors;   

DOI  :  10.3389/fnagi.2018.00194

来源: DOAJ

【 摘 要 】

Here, we tested the claim that nicotine attenuates the signs of brain dysfunction in the model of brain aging induced by D-galactose (DGal) in mice. We administered nicotine at doses of 0.1, 0.5 and 1 mg/kg by the subcutaneous (s.c.) or at 0.1 mg/kg by the intranasal (i.n.) routes in mice that had received DGal at the dose of 500 mg/kg subcutaneous (s.c.) for 6 weeks. We assessed animal withdrawal signs as the number of presented somatic signs, thermal hyperalgesia, elevated plus maze (EPM) and open field tests. We evaluated spatial memory and recognition with Barnes maze and novel object recognition (NOR) tests. We tested brain tissue for reactive oxygen species (ROS), mitochondrial membrane potential, caspase-3, Bax, Bcl-2, cytochrome C, brain-derived neurotrophic factor and nerve growth factor levels. Nicotine administration in model groups (0.5 mg/kg s.c. and 0.1 mg/kg i.n. doses) significantly attenuated impairment of spatial and episodic memories in comparison to normal saline-received model group. These doses also reduced mito-oxidative damage as well as apoptosis and raised neurotrophic factors level in model groups in comparison to normal saline-received model group. The 1 mg/kg s.c. dose nicotine revealed withdrawal signs compared with the other nicotine-received groups. Nicotine at specific doses and routes has the potential to attenuate age-related cognitive impairment, mito-oxidative damage, and apoptosis. The doses raise neurotrophic factors without producing withdrawal signs.

【 授权许可】

Unknown