Mineral deficiency found in brain of Huntington’s patients in study
But researchers warn of danger of self-medicating with selenium
People with Huntington’s disease were found to have a widespread deficiency of selenium — a trace mineral found naturally in foods such as seafood and Brazil nuts — in their brains, revealing a new potential therapeutic target, according to researchers.
Alterations in the levels of other biologically active metals, including sodium, calcium, potassium, and zinc, also were found in multiple brain regions of Huntington’s patients.
“The most striking finding is the deficiency of selenium in every part of the brain we studied,” Garth Cooper, PhD, the study’s senior author at The University of Manchester, in the U.K., said in a university press release, adding, “Because selenium was deficient in all regions of the brain, that might mean it could be easier to one day target therapeutically, as it’s very hard to home in on specific brain regions.”
While the researchers suggested supplements of selenium may represent a potential Huntington’s treatment, Melissa Scholefield, PhD, the study’s first author, also at Manchester, emphasized that “it is dangerous to self-medicate with supplements.”
Only trace or very small amounts of these elements are needed in the body, and the blood-brain barrier — a highly-selective membrane that prevents microbes and large molecules in circulation from entering the brain and spinal cord — “could mean these … elements might build up in someone’s blood stream, with potentially toxic effects,” Scholefield said.
The study, “Widespread selenium deficiency in the brain of cases with Huntington’s disease presents a new potential therapeutic target,” was published in the journal eBioMedicine.
Deficiency in mineral selenium found in all brain regions tested
Huntington’s is a genetic neurodegenerative disorder marked by a wide range of symptoms that include uncontrolled body movements, cognitive impairment, and psychiatric problems.
Previous studies have suggested alterations in the levels of biologically active metals or elements with metal-like properties in the blood and brains of Huntington’s patients. These include, in addition to selenium, such metals and elements as copper, manganese, zinc, iron, and sodium.
Many of these molecules are essential for the function of certain antioxidants that neutralize oxidative stress, a type of cellular damage implicated in Huntington’s.
Now, Cooper and Scholefield, along with colleagues at the University of Auckland, in Australia, measured the concentrations of nine metals or metal-like molecules in brain samples from nine deceased Huntington’s patients and nine age- and sex-matched deceased unaffected people, who served as controls.
The measured substances were calcium, copper, iron, magnesium, manganese, potassium, selenium, sodium, and zinc. Tissue samples covered 11 brain regions, including those “traditionally considered to be severely affected, moderately affected, and relatively spared in HD [Huntington’s disease],” the team wrote.
According to Scholefield, “This is the first known study which investigated metals simultaneously across many regions of the HD brain in the same cohort [group of patients].”
The analysis revealed significantly lower selenium levels in Huntington’s patient samples relative to those from controls, and in every brain region investigated. Selenium levels were lowest in the putamen and the entorhinal cortex, two brain regions largely affected by Huntington’s.
“HD brains showed widespread [selenium] decreases despite differing levels of neurodegeneration between regions,” the researchers wrote.
The findings demonstrated that selenium “plays an important role in protection against oxidative stress and mitochondrial dysfunction — both of which are known to occur in the [development] of HD,” the team wrote. Impairments in mitochondria, which serve as a cell’s powerhouse, and problems in cellular compartments have been associated with Huntington’s in earlier research.
Here, Huntington’s patients also showed significantly higher ratios between sodium and potassium, indicating either more sodium or less potassium, relative to healthy controls in all but one brain region. That region, the substantia nigra, is involved in voluntary movement.
Both of these ions play an essential role in nerve cell communication, the team noted. And like like selenium, these alterations were not limited to brain regions with high levels of neurodegeneration.
Researchers also find deficiency in other metal, mineral levels
Levels of calcium were significantly higher in five brain regions of Huntington’s patients compared with controls, and zinc levels were significantly higher in three brain regions. Manganese, iron, and copper were elevated in one region alone among Huntington’s patients.
No changes in brain magnesium levels were noted between Huntington’s patients and healthy controls.
“Taken together, these results provide support for several substantial metallomic alterations in the HD brain,” the researchers wrote.
Scholefield said the new findings support ones seen in previous studies in mice.
“We think the changes we found … could contribute to several [disease-associated] mechanisms, including mitochondrial dysfunction, oxidative stress, and blood-brain barrier dysfunction,” Scholefield said.
[Selenium] deficiency presents a promising therapeutic target due to its presence in 11 out of 11 investigated brain regions.
Overall, the researchers concluded that “[selenium] deficiency presents a promising therapeutic target due to its presence in 11 out of 11 investigated brain regions.” They added that “the development of a safe and effective drug targeting [selenium] deficiency in the HD brain should be investigated further.”
One limitation of this study, as noted by Cooper, was its relatively small sample size.
According to Cooper, that means that “the results from [this] human brain study should be treated as preliminary.”
“Further studies determining the time course, cause, and downstream effects of selenium alterations in HD may eventually present a potential therapeutic target for the treatment of this disease,” Cooper said.