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Introduction: Nicotine is a liquid alkaloid from tobacco plant. It is well known that nicotine is an agonist on nicotinic acetylcholine receptors (nAChR) in the brain. On the other hand, nicotine acts on two subunits (nAChRα9 and nAChRα10) as a receptor antagonist. Nicotine is abused commonly as an addictive drug and shows drug-reinforcement, and relapse following abstinence. Also, nicotine shows tolerance, sensitization, and physical and physiological dependency. Nicotine has some unpleasant withdrawal symptoms such as mood disorders, anxiety, irritability, difficulty concentrating, and insomnia. Nicotine has a low therapeutic index and is mild analgesic and sedative. The effect of Cotinine, active metabolite of nicotine, on Aβ1-42 neurotoxicity was investigated. Cotinine possesses a longer plasma half-life, lower toxicity and it is a partial agonist of the nicotinic acetylcholine receptors (nAChR). Conclusion: Some in vitro and in vivo studies indicate that Cotinine prolongs the survival of cortical neurons exposed to Aβ1-42. These results indicate that cotinine has a neuroprotective effect by inhibition of the formation of amyloid beta in the brain. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder characterized by the formation of beta-amyloid plaques in the brain. Loss of neurons is one of the important features of this disease, which is accompanied by memory and cognitive disorders. In this study, the effect of ghrelin on different pathways of cell death, including apoptosis, necroptosis and autophagy, was investigated in AD model rats induced by βamyloid. Methods and Materials: Experiments were performed on male Wistar rats with a weight range of (250±20). Animals were randomly divided into five groups including sham control, ghrelin, beta-amyloid and betaamyloid+ghrelin. Bilateral administration of β-amyloid (5 μg/10 μl) into the hippocampus was used to induce Alzheimer's disease. Ghrelin (80 µg/kg) was injected intraperitoneally for ten consecutive days. Then the memory of rats was evaluated by the passive avoidance method and the Morris water maze. In the end, the hippocampal tissue was extracted and subjected to histopathological study. Also, the expression of Bax protein (apoptosis), Bcl-2 protein (anti-apoptotic), necroptosis proteins RIP1K and RIP3K, and autophagic marker Beclin-1 were investigated by western blot method. Results: The findings of this study showed that ghrelin improves memory impairment in Alzheimer's rats and reduces the expression of Bax (apoptotic), RIP1K and RIP3K (necrotic) proteins. It also increases the expression of Bcl-2 (anti-apoptotic) and the Bax/Bcl-2 ratio. Beclin-1 protein expression is also significantly increased by ghrelin treatment (p<0.05). Conclusion: These results show that peripheral administration of ghrelin can prevent cell death and protect neurons by inhibiting apoptosis and necroptosis and autophagy promotion. Therefore, it should play a role in preventing the progression of Alzheimer's disease [ABSTRACT FROM AUTHOR]