Revisiting nicotine’s role in the ageing brain and cognitive impairment

Majdi, Alireza; Kamari, Farzin; Vafaee, Manouchehr Seyedi; Sadigh-Eteghad, Saeed

doi:10.1515/revneuro-2017-0008

Cited by 29 publications

(26 citation statements)

References 161 publications

(183 reference statements)

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“…Nicotine distributes to the brain shortly after peripheral administration (whether intraperitoneal, intravenous, oral, or subcutaneous) with maximum between 30 and 60 min, and can be detected in the CNS as late as 4 h after injection (Crooks and Dwoskin, 1997). In contrast to distribution after peripheral administration, smoking causes nicotine to massively distribute to the bloodstream and from there to the brain in 10–20 s (Majdi et al, 2017). Due to the prominence of the base and associated lipid solubility, nicotine readily penetrates the blood-brain barrier (BBB) at physiological pH (Oldendorf et al, 1979; Tega et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

“…We also excluded studies that evaluated the effects of nicotine (rather than its metabolites) on the cognitive function. We examined the effects of nicotine in a previous publication (Majdi et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

“…As the target of nicotine and its metabolites, nicotinic acetylcholine receptors (nAChR) modulate specific aspects of learning and memory (Majdi et al, 2017). Among different subtypes of nAChR, the α 7 subtype may be mainly responsible for the procognitive and neuroprotective properties of acetylcholine (Sadigh-Eteghad et al, 2014; Wong et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review

et al. 2019

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Background: The alleged procognitive effects of nicotine and its metabolites in brain are controversial.Objective: Here, we review the pharmacologically active metabolites of nicotine in brain and their effects on neuronal mechanisms involving two main cognitive domains, i.e., learning and memory.Methods: We searched Embase, Medline via PubMed, Scopus, and Web of Science databases for entries no later than May 2018, and restricted the search to articles about nicotine metabolites and cognitive behavior or cognitive mechanisms.Results: The initial search yielded 425 articles, of which 17 were eligible for inclusion after application of exclusion criteria. Of these, 13 were experimental, two were clinical, and two were conference papers.Conclusions: The results revealed three pharmacologically active biotransformations of nicotine in the brain, including cotinine, norcotinine, and nornicotine, among which cotinine and nornicotine both had a procognitive impact without adverse effects. The observed effect was significant only for cotinine.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review

et al. 2019

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“…Nicotine (NIC) is an alkaloid extracted from Nicotiana tabacum and an exogenous agonist of nAChRs [ 15 ]. Accumulated evidence from animal and clinical studies showed that NIC has cognitive-enhancing effects, improving performance in several domains of cognition, including attention, learning, and working memory [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in Aβ25-35-Induced Rat Model of Alzheimer’s Disease

et al. 2020

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The nicotinic derivatives, cotinine (COT), and 6-hydroxy-L-nicotine (6HLN), showed promising cognitive-improving effects without exhibiting the nicotine’s side-effects. Here, we investigated the impact of COT and 6HLN on memory impairment and the oxidative stress in the Aβ25-35-induced rat model of Alzheimer’s disease (AD). COT and 6HLN were chronically administered to Aβ25-35-treated rats, and their memory performances were assessed using in vivo tasks (Y-maze, novel object recognition, and radial arm maze). By using in silico tools, we attempted to associate the behavioral outcomes with the calculated binding potential of these nicotinic compounds in the allosteric sites of α7 and α4β2 subtypes of the nicotinic acetylcholine receptors (nAChRs). The oxidative status and acetylcholinesterase (AChE) activity were determined from the hippocampal tissues. RT-qPCR assessed bdnf, arc, and il-1β mRNA levels. Our data revealed that COT and 6HLN could bind to α7 and α4β2 nAChRs with similar or even higher affinity than nicotine. Consequently, the treatment exhibited a pro-cognitive, antioxidant, and anti-AChE profile in the Aβ25-35-induced rat model of AD. Finally, RT-qPCR analysis revealed that COT and 6HLN positively modulated the bdnf, arc, and il-1β genes expression. Therefore, these nicotinic derivatives that act on the cholinergic system might represent a promising choice to ameliorate AD conditions.

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“…Nicotine is a nAChR agonist and pharmacological chaperone that stimulates cholinergic activity in the brain (Jackson et al, 2010 ; Sadigh-Eteghad et al, 2015a ). It has been shown that nicotine improves working memory, executive function, and cognitive performance, both in human and animals (Rushforth et al, 2011 ; Jansari et al, 2013 ; Vafaee et al, 2015 ; Majdi et al, 2017 ). Nicotine also reduces reactive oxygen species (ROS) generation by brain mitochondria and prevents oxidative stress in a dose-dependent manner (Cormier et al, 2003 ; Guan et al, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

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

Majdi

Sadigh-Eteghad

Talebi

et al. 2018

Front. Aging Neurosci.

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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.

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Revisiting nicotine’s role in the ageing brain and cognitive impairment

Cited by 29 publications

References 161 publications

Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review

Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review

Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in Aβ25-35-Induced Rat Model of Alzheimer’s Disease

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

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