Our results show that low plasma selenium concentrations are associated with subtle neurological impairments reflected in soft neurological signs. Such impairments were seen in coordination tests of both upper and lower extremities. Our observation is consistent with findings of other research showing higher prevalence of disability in the lower plasma selenium group (16
). A somewhat similar finding was also found in participants with low vitamin E by another researcher (26
). Given that the InChianti study was conducted in community-dwelling elderly we chose to focus on minor neurological findings, bearing potential relation to the SN system.
The average selenium concentration in our study sample was relatively low, 74.5μg/L (0.94 μmol/L). These values are consistent with other studies conducted in Italy. For example, in the Veneto study (27
) the mean plasma selenium concentrations were 65.2 μg/L (0.82 μmol/L) in adults and 89.1 μg/L (1.12 μmol/L ) and 68.4 μg/L (0.86 μmol/L ) in adults aged 65–89 and ≥ 90 respectively from Bologna (28
). In other countries, and particularly in the US, selenium concentrations are higher, depending on the area where the assessment was conducted (29
). In the third National Health and Nutrition Examination Survey, Phase 2 (1991–1994) (NHANES III) the mean serum selenium among non-anemic and anemic adults was 127.3 μg/L (1.60 μmol/L) and 120.1 μg/L (1.51 μmol/L) respectively (30
). These differences may reflect different assay methods as well as differences in bioavailability of selenium from foods that may stem from the amount of selenium in the soil (30
From a biological point of view, the findings in this study may reflect the putative protective effect of selenium against oxidative damage in neuronal cells. A wealth of scientific evidence relates selenium to the anti-oxidative mechanisms. Much of the confusion related to the popular term “anti-oxidants” stems from the generality of this term. In fact, anti-oxidants should be grouped according to several categories by their functions and chemical structures, which are highly divergent. Selenium, as previously mentioned, is an element, with close resemblance to sulfur, which serves as a component of the active site of several enzymes. The common feature of these enzymes is their ability to “disarm” super-oxide molecules (8
). From a theoretical standpoint, even though aging is not fully explained by any single mechanism, it is widely believed that oxidative damage plays a role in the aging process.
The SN system seems an important indicator of oxidative damage in the brain. First, it contains a population of dopaminergic neurons, which are unique, highly specialized cells, with a specific neurological function. Thus, an injury to dopaminergic neurons in the substantia-nigra is far more likely to be clinically relevant than a similar size injury elsewhere in the brain. Secondly, dopaminergic neurons are highly susceptible to oxidative damage given the nature of the biochemical reactions in these cells (25
). Specifically, the dopamine molecule itself has the potential to induce oxidative damage, unless rapidly sequestered in the cell (5
). On the other hand, other parts of the brain are also susceptible to oxidative damage. The cerebellum, which is highly important in movement modulation, is also a target for such hits. Ataxia-telangiectasia (A-T), a hereditary illness is a suitable example. A-T is an autosomal recessive disorder caused by mutations in the ATM gene. The hallmark of A-T is fulminant degeneration of cerebellar Purkinje cells accompanied by a progressive ataxia with features of both cerebellar and basal ganglia dysfunction. Recently, it has been suggested that abnormalities in redox status contribute to the A-T phenotype. In a recent study (13
), microscopic examination revealed elevated superoxide levels in cerebellar Purkinje cells and nigral dopaminergic neurons but not cortical neurons. These findings map increased superoxide levels onto the vulnerable neuronal populations selectively affected in A-T.
Our findings are also consistent with findings from animal studies using the methamphetamine nigrostriatal toxicity model. A study by Kim (11
) showed prevention and even reversal of functional and anatomic nigrostriatal destructive changes using dietary enrichment with Se. This study is the most extensive one done in animals and its results are very convincing. Nonetheless, it is worth remembering that the methamphetamine toxicity model may not be fully analogous to degenerative Parkinson’s disease (3
The cross-sectional design of the current study limits causal inference that can be drawn from these findings. Indeed, reverse causation is possible as SN dysfunction might cause malnutrition leading to lower Se levels. This would be particularly of great concern in various patient populations (e.g., those diagnosed with Parkinsonism); however, our study sampled community-dwelling older adults and we excluded participants with Parkinson’s diagnosis from the analyses of neuro-motor performance, reducing concern for reverse causality. Nonetheless, this study is observational and constitutes the first level of scientific investigation into the role of selenium in protecting the EPS. Thus the findings should be taken cautiously. The next phase should be a longitudinal cohort study, which would add a dimension of temporal sequence to this association. Finally, a neurological clinical trial could evaluate the potential benefit of increasing selenium concentrations.