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Nicotine May Protect the Brain from Toxic Trace Metals Linked to Parkinson’s, Cell Study Finds

nicotine study

Nicotine may protect the brain from manganese and iron metal trace elements thought to be involved in the onset of Parkinson’s disease, a study based on a disease cell model reported.

The study, “Nicotine protects against manganese and iron-induced toxicity in SH-SY5Y cells: Implication for Parkinson’s disease,” was published in Neurochemistry International.

Parkinson’s is characterized by the gradual loss of dopaminergic neurons in the substantia nigra — a region of the brain responsible for movement control — leading to motor and cognitive impairments.

Although the exact causes of Parkinson’s are not yet fully understood, scientists believe the accumulation of metal trace elements, such as manganese and iron, could play a role in its onset. At low concentrations, these elements are crucial for cell growth and physiological functions; indeed, they are important for all growth and healthy workings of the body. But at high levels, they become toxic, and have been associated with several neurodegenerative disorders, including Parkinson’s.

Nicotine, a potent stimulant originally found in plants that activates the nicotinic acetylcholine receptor (nAChR) in the brain, has been shown to protect dopaminergic neurons from damage caused by different types of toxins. However, no study had addressed possible neuroprotective effects of nicotine against specific metal trace elements.

The new study from Howard University College of Medicine examined the effects of nicotine on toxic manganese and iron elements in a neuroblastoma cell line (SH-SY5Y), a standard in vitro model to study Parkinson’s disease cells, due to their dopaminergic activity.

When researchers exposed SH-SY5Y cells to high concentrations of manganese or iron for a day, toxicity levels increased by 30% and 35%, respectively. Pretreatment with nicotine was seen to completely prevent these toxic effects.

As expected, nicotine’s neuroprotective properties against toxic trace elements were lost when researchers used different types of nicotinic receptor antagonists (molecules that block the activity of nAChRs). This was true for “dihydro-beta erythroidine (DHBE), a selective alpha4-beta2 subtype antagonist and methyllycaconitine (MLA), a selective alpha7 antagonist,” the study noted.  

“In summary, the results of this study provide evidence for neuroprotective effects of nicotine against toxicity induced by Mn [manganese] or Fe [iron] in a cellular model of PD [Parkinson’s disease],” the researchers wrote.

“Moreover, both high and low affinity nicotinic receptors (i.e., alpha4-beta2 and alpha7 subtypes) appear to mediate the effects of nicotine. Thus, utility of nicotine or nicotinic agonists in trace element-induced Parkinson-like syndrome may be suggested,” they concluded.

The post Nicotine May Protect the Brain from Toxic Trace Metals Linked to Parkinson’s, Cell Study Finds appeared first on Parkinson’s News Today.

Treatment With AZD0328, Nicotine Loses Effectiveness as Parkinson’s Progresses, Study Shows

AZD0328 and Parkinson's

 

AZD0328 and nicotine, two nicotinic receptor agonists, lose their effectiveness in treating involuntary muscle movements as a consequence of long-term levodopa treatment throughout the course of Parkinson’s disease, a mouse study finds.

The study, “Dyskinesia and brain-derived neurotrophic factor levels after long-term levodopa and nicotinic receptor agonist treatments in female mice with near-total unilateral dopaminergic denervation,” was published in BMC Neuroscience.

The main cause of the motor symptoms in Parkinson’s disease is a lack of dopamine — a brain chemical — resulting from a loss of dopaminergic neurons in the substantia nigra, a brain area responsible for controlling voluntary muscle movements.

Levodopa, a dopamine replacement therapy, is often recommended to ease Parkinson’s symptoms. However, levodopa can have multiple side effects, including involuntary muscle movements, also known as levodopa-induced dyskinesia (LID).

Previous studies have shown that treatment with nicotinic acetylcholine receptor (nAChRs) agonists alleviate LID in different animal models of disease. However, it is still not clear whether treatment with nAChRs is effective once dopamine-producing neurons have been destroyed. nAChRs are a type of receptors found in nerve cells that control the transmission of electrical signals.

Studies have also suggested that high levels of brain-derived neurotrophic factor (BDNF) — a protein whose main function is to protect dopaminergic neurons — could be linked to LID.

Now, researchers from the University of Helsinki tested the effectiveness of AZD0328 and nicotine, two different nAChR agonists, in female mice that developed LID after long-term treatment with levodopa.

At the beginning of the experiments, animals were injected with oxidopamine — a neurotoxin that destroys dopamine-producing neurons — on one side of the brain (damaging only one brain hemisphere) to mimic the loss of dopaminergic neurons associated with Parkinson’s disease. A month later, mice started treatment with levodopa (6 mg/kg) that lasted until the end of the experiments.

After treatment with nAChR agonists, BDNF levels were measured in two regions of the brain: the prefrontal cortex and striatum. The prefrontal cortex is a region responsible for higher thought processes, such as decision making, planning and reasoning, while the striatum is involved in motor coordination.

Findings revealed that five-day treatment with increasing doses of AZD0328 (from 0.03 mg/kg to 1.0 mg/kg) failed to alleviate LID in these animals. The same was observed in mice treated with nicotine for 10 weeks.

No difference in BDNF levels between the lesioned and intact brain hemispheres was observed in either brain area. BDNF levels in the lesioned striatum were linked to higher LID severity.

“The observed correlation between BDNF and LID represents further evidence for a role for BDNF in LID,” researchers said. “However, the present findings do not directly support the hypothesis that LID is caused by a levodopa-induced elevation of corticostriatal BDNF that is further enhanced in conditions of dopaminergic denervation [loss].”

Nicotine treatment successfully decreased BDNF levels in the prefrontal cortex, but failed to do so in the striatum.

Altogether, these findings suggest that “a partially intact” dopaminergic circuitry seems to be required for the effectiveness of nAChR agonists in the treatment of LID and that “nAChR agonists may lose [their] effectiveness as the disease progresses.”

“These findings may be important to account for when drafting potential future strategies for the treatment of late-stage Parkinson’s disease with nAChR ligands,” researchers concluded.

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