Selenium Mineral Levels Increased in Cerebrospinal Fluid of Parkinson’s Patients, Research Suggests

Selenium Mineral Levels

People with Parkinson’s disease may have higher levels of selenium — a mineral with antioxidant properties — in their cerebrospinal fluid, the liquid that surrounds the brain and spinal cord, a study suggests.

The research, “Selenium level does not differ in blood but increased in cerebrospinal fluid in Parkinson’s disease: a meta-analysis,” was published in the International Journal of Neuroscience.

Although the exact trigger for Parkinson’s disease still remains to be identified, research indicates that its causative mechanism involves genetics, ageing, deficiencies in mitochondria — cells’ powerhouses — and oxidative stress.

Oxidative stress is an imbalance between the production of harmful free radicals — toxic molecules that are the natural byproducts of ongoing biochemical reactions in the body — and the ability of cells to detoxify. It results in cellular damage.

Such molecular and cellular changes eventually lead to the progressive death of dopamine-producing neurons in Parkinson’s disease.

Selenium is a critical mineral that has antioxidant properties, is essential for brain health, and plays a role in immune functions as well as anti-cancer activity.

Despite its antioxidant properties, conflicting evidence exists in regard to the role selenium plays in Parkinson’s. Several studies have found higher selenium levels in people with the disease, compared with healthy individuals, but others have shown regular or decreased levels of selenium in this patient population.

Now, a team led by researchers at Zhengzhou University, in China, evaluated all available evidence regarding selenium levels in the blood and cerebrospinal fluid, known as CSF, in the context of Parkinson’s disease.

The investigators searched the records of three biomedical databases that included studies from 1995 up through October 2019, examining associations between selenium levels and Parkinson’s risk.

The team analyzed a total of 12 case-control studies, which involved 601 Parkinson’s patients (mean age 57.62 to 70 years) and 749 healthy people (controls).

Compared with the healthy controls, the Parkinson’s patients had significantly higher selenium levels in their cerebrospinal fluid, the results showed. No differences were found in blood selenium concentration between the two groups.

“We speculate that oxidative stress conferred by the pathogenesis [disease characteristics] of [Parkinson’s disease] can lead to higher selenium levels and increased antioxidant capacity as a protective mechanism,” the researchers said.

While the investigators said their “results are convincing,” they did report great disparity between the studies analyzed. Such heterogeneity could be due to several factors, the researchers said, including the distinct methods by which the studies selected participants and quantified selenium levels, and inadequate matching between patients and healthy controls in each study. In addition, some of the studies lacked an analysis that minimized potential confounding factors like age, gender ratio, treatment, and the presence of other diseases — all of which might affect selenium levels in the body, the researchers said. Moreover, the analyzed studies were carried out in dozens of countries.

In these types of meta-analyses, when researchers combine the results of multiple scientific studies, there is always the possibility of publication biases, the investigators noted. Such publication bias can occur because studies with significant, or positive, findings are more likely to be published than studies with negative findings. This means that any meta-analysis or literature reviews based on published data could potentially be biased as a result.

In this case, however, the team used a specific statistical test — called a Begg’s test — to assess for this type of asymmetry of data and found no significant publication bias.

The researchers concluded that Parkinson’s patients may have higher selenium levels in their cerebrospinal fluid. However, further study is necessary as this finding, although significant, was associated with great data heterogeneity, they said.

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Changes in Fatty Acid Metabolism May be Linked to Parkinson’s Severity, Rat Study Finds

fatty acid metabolism

The metabolism of certain types of fats, namely palmitic acid and stearic acid commonly found in animal and vegetable fats and oils, may be altered in Parkinson’s disease, according to a study in rats.

The study, “Palmitate and Stearate are Increased in the Plasma in a 6-OHDA Model of Parkinson’s Disease,” was published in the journal Metabolites.

Studying small molecules produced by metabolism — commonly known as metabolites — within cells, biofluids, tissues, or organisms holds promise for the discovery of potential diagnostic biomarkers, which may shed light on susceptibility to Parkinson’s, disease prognosis, and therapeutic response to treatment.

In fact, an increase in metabolites of fatty acid-related molecular pathways has been reported in the plasma and cerebrospinal fluid of Parkinson’s patients, which correlated with disease progression. An increase in amino acid (protein’s building blocks) metabolism in urine samples of Parkinson’s patients has also been reported.

Evidence also suggests that metabolic profiling of cerebrospinal fluid is useful for distinguishing between newly diagnosed Parkinson’s patients and healthy individuals.

Although studies indicate that an array of molecular changes have the potential to become disease biomarkers, there is still no consensus on which markers are more informative from a diagnostic, prognostic, or even therapeutic point of view.

King’s College London researchers set out to investigate changes in brain, plasma, and liver metabolism of a rat model of Parkinson’s to discover small molecules that are associated with dopaminergic cell loss — a hallmark of the disease.

Thirteen rats were injected on one side of the brain only (unilaterally) with 6-hydroxydopamine (6-OHDA), a neurotoxin that causes the death of dopamine-producing (dopaminergic) neurons. Another 13 animals were injected with saline into the same brain region and used as a control sample.

Two weeks after injection, the animals were given two behavioral tests for researchers to assess their motor function.

“Unilateral lesions of 6-OHDA successfully resulted in the manifestation of motor symptoms, as observed by [behavioral tests] indicating the intensity of the lesions,” the researchers wrote.

Tissue analysis of the animals’ substantia nigra — a midbrain area important for muscle control that is commonly damaged in Parkinson’s disease — revealed that rats injected with 6-OHDA only had 28% of dopaminergic neurons on the injection side, compared with the other side that was not injected. Control samples had similar dopaminergic neuronal cell count on both brain sides.

Scientists then performed a metabolic analysis on the animals’ plasma, midbrain, cerebellum, and liver samples.

Results showed significantly high plasma levels of palmitic acid and stearic acid, both saturated fatty acids, within the Parkinson’s disease modeling group, which were found to be associated with motor dysfunction.

Lipid metabolism involves the degradation of triglycerides, a type of fat, into smaller chain fatty acids and subsequently into monoglycerides (glycerol molecule combined with a fatty acid) by specific enzymes.

Monoglyceride forms of palmitic acid and stearic acid, also known as monopalmitin and monostearin, respectively, were reduced in the midbrain of animals injected with 6-OHDA. Low levels of myo-inositol, a sugar alcohol molecule that has been used to decrease hormonal changes in polycystic ovary syndrome, were also found in the midbrain.

Compared with the control group, 6-OHDA rats showed a tendency toward lower levels of monopalmitin, monostearin, and myo-inositol in the cerebellum, but statistical significance was not reached.

No fatty acid-related molecular changes were observed in the animals’ livers.

“Our results show that saturated free fatty acids, their monoglycerides and myo-inositol metabolism in the midbrain and enteric circulation are associated with 6-OHDA-induced [Parkinson’s disease] pathology,” the researchers wrote.

“Changes of the midbrain metabolites may be associated with neuronal loss elicited by 6-OHDA while palmitic acid and stearic acid showed a high correlation with behaviour tests, indicating a possible association with disease severity,” they said.

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