Examining the Neuroprotective Effects of Nicotine

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Furthering research on Alzheimer’s disease, Alkadhi (2011) studied the effects of psychosocial stress and nicotine in the development of the disease. Previous research suggested environmental factors, such as chronic stress, might have an important role in the severity and time of onset of Alzheimer’s. Using an animal model of Alzheimer’s disease, and recognizing that administration of the disease in animals did not reproduce to the same complexity as the human form of Alzheimer’s disease, chronic stress was tested in a group of rats. Results showed that the group of rats who were exposed to both chronic stress and the disease showed significantly more short-term memory impairments than control rats. Although six weeks of psychosocial stress did not seem to impair long-term memory or the learning abilities of control rats, the infusion of disease in rats in the chronic stress group caused deficits in long-term memory. The extent of these effects was significantly more severe than the effects of the disease infusion alone. Rats who received nicotine treatment not only had fewer symptoms of Alzheimer’s disease but also had lowered levels of chronic stress (Alkadhi, 2011).

Alkadhi (2011) also proposed that nicotine slows symptoms of Alzheimer’s through offsetting the inflammatory effects of the disease. As one of the first processes to occur after injury, inflammation had previously been shown to clear off lesion areas. Over time, however, inflammation could contribute to negative effects such as neurotoxicity, a condition that seemed to worsen Alzheimer’s disease. Along with reducing the potentially harmful effects of inflammation, nicotine’s overall effect on chronic stress was found to be an important indication of severity in a rat model of Alzheimer’s disease. Evidence suggested that chronic stress lead to greater severity, and faster progression of the disease unless treated with nicotine, which mitigated the effects (Alkahadi, 2011).

In recognizing a negative relationship between the administration of tobacco and the prevalence of Parkinson’s disease, Barreto, Iarkov, and Moran (2014) suggested that compounds that were derived from tobacco could offset the disease. Although nicotine had often been recognized as being responsible for the positive neurological effects of tobacco in Parkinson’s disease, it was proposed that other metabolites of nicotine could also enhance the brain after administration. Using a rodent model of Parkinson’s to study the effects of nicotine and its derivatives, it was found that nicotine and its compounds decreased oxidative stress and brain inflammation, and increased synaptic plasticity. Outside of the brain, these effects caused increases in mood, improved motor skill, and enhanced memory in rats affected by the disease (Barreto et al., 2014).

Barreto et al. (2014) also discussed the safety concerns surrounding nicotine use, and proposed that reducing the dose required for therapeutic use, counteracting the drug with natural extracts, or counteracting nicotine with other drugs could potentially be less dangerous ways to reap the protective effects. It was also noted that for any method to be effective, nAChR activation was necessary – findings that agreed with Nakamura et al.’s (2001) study.

Another neurodegenerative disease that nicotine could positively influence is multiple sclerosis. Characterized as an autoimmune disease with no known cure, Naddafi, Haidari, Azizi, Sedaghat, and Mirshafiey (2013) explored whether nicotine treatment could slow progression of multiple sclerosis. Through experimentation on an animal model, mice were administered with nicotine and an up-regulation of nAChRs was observed. Results also displayed a treatment group to have decreased inflammation of the brain in comparison to a control group. A prevention group of mice were also studied and results furthered the evidence for nicotinic treatment. Prevention group mice, who were treated with nicotine a week before being immunized with the disease and continued treatment for two weeks following immunization, showed even less inflammation than the treatment group, which proved consistent and similar to Alkadhi’s (2011) findings on nicotine and Alzheimer’s. The potential of nicotine therapy, therefore, seemed to include multiple sclerosis and could be promising for patients suffering from the disease (Naddafi et al. 2013).

Huang, Parameswaran, Bordia, McIntosh, and Quik (2009) conducted research that acknowledged the neuroprotective effects of nicotine on diseases such as the ones previously discussed, and attempted to further it by exploring potential for a neuroregenerative effect. Recognizing a gap in research, Huang et al. (2009) sought to determine whether the enhancing effects of nicotine on striatal dopamine levels was due to neuroprotective or neurorestorative effects, or both. The nigrostriatal region of the brains of both rats and monkeys was damaged, and nicotine was administered through drinking water. Results suggested that when administered to both animals, nicotine treatment protected against damage to the nigrostriatal region when lesioning occurred before administration of the drug. When nicotine was consumed only after lesioning, no restorative effects were observed. Huang et al. (2009) concluded that pre-treating both animals with nicotine enhanced striatal dopamine levels, and increased the number of nAChRs, so the brain was better protected when subsequently damaged.

Huang et al. (2009) also observed that when nicotine was administered after brain damage was completed, rotational behavior in rats did not decrease after exposure to the drug. This, along with no increases in striatal integrity, suggested that nicotine post-treatments were not neurorestorative in rats. Similar post-treatment effects were observed in monkeys. It was therefore concluded that nicotine could not restore damaged neurons, but rather blocked ongoing damage to the striatal region. In terms of implications, Huang et al. (2009) indicated that treatment with nicotine during the early stages of Parkinson’s disease might prevent subsequent degeneration.

Strong evidence has suggested the therapeutic effects of nicotine on neurodegenerative diseases, and the metabolites of nicotine probably to play a role in its neuroprotective actions, as previously mentioned in Bareto et al.’s (2014) research. Buccafusco & Terry (2003) attempted to discover the role of cotinine, which has been suggested to have effects on the cognitive behavioural functions in both humans and animals. As the primary metabolite of nicotine, cotinine does not appear to trigger withdrawal symptoms, nor does it seem to have the rewarding properties that nicotine offers a user. With a half-life that lasts much longer in the body