Copper chelator cuprizone (CPZ) is neurotoxicant, which selectively disrupts oligodendroglial respiratory chain, leading to oxidative stress and subsequent apoptosis. Demyelination is, however, followed by spontaneous remyelination owing to the activation of intrinsic CNS repair mechanisms. To explore the participation of metallothioneins (MTs) in these processes, in this study we analyzed the expression profiles of MT-I/II and their receptor megalin (low-density lipoprotein receptor related protein-2) in the brain of mice subjected to different protocols of CPZ feeding. Experiments were performed in female C57BL/6 mice fed with 0.25% CPZ during 1, 3 and 5 weeks. They were sacrificed immediately after feeding with CPZ or 2 weeks after the withdrawal of CPZ. The data showed that CPZ-induced demyelination was followed by high astrogliosis and enhanced expression of MTs and megalin in white (corpus callosum and internal capsule) and gray matter of the brain (cortex, hippocampus, and cerebellum). Moreover, in numerous cortical neurons and progenitor cells the signs of MT/megalin interactions and Akt1 phosphorylation was found supporting the hypothesis that MTs secreted from the astrocytes might directly affect the neuronal differentiation and survival. Furthermore, in mice treated with CPZ for 5 weeks the prominent MTs and megalin immunoreactivities were found on several neural stem cells and oligodendrocyte progenitors in subgranular zone of dentate gyrus and subventricular zone of lateral ventricles pointing to high modulatory effect of MTs on adult neuro- and oligodendrogenesis. The data show that MT I/II perform important cytoprotective and growth-regulating functions in remyelinating processes activated after toxic demyelinating insults.

Iron is an essential element that participates in numerous cellular processes. Any disruption of iron homeostasis leads to either iron deficiency or iron overload, which can be detrimental for humans’ health, especially in elderly. Each of these changes contributes to the faster development of many neurological disorders or stimulates progression of already present diseases. Age-related cellular and molecular alterations in iron metabolism can also lead to iron dyshomeostasis and deposition. Iron deposits can contribute to the development of inflammation, abnormal protein aggregation, and degeneration in the central nervous system (CNS), leading to the progressive decline in cognitive processes, contributing to pathophysiology of stroke and dysfunctions of body metabolism. Besides, since iron plays an important role in both neuroprotection and neurodegeneration, dietary iron homeostasis should be considered with caution. Recently, there has been increased interest in sex-related differences in iron metabolism and iron homeostasis. These differences have not yet been fully elucidated. In this review we will discuss the latest discoveries in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke.

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Purpose: To examine the feasibility and possible effect of an 8-week exercise program on sleep quality, insomnia and psychological distress in individuals with multiple sclerosis (MS). Methods: Twenty-four individuals with MS were recruited into a controlled pre-post feasibility study and divided into 2 groups: exercise (n = 13; Expanded Disability Status Scale (EDSS): 1.0–7.5) and a related control group with no exercise (n = 11; EDSS: 1.0–7.0). The exercise group performed combined upper limb, lower limb and breathing exercises in a controlled group (2d/week, 60 min/session) for 8 weeks. Participants were administered measures to evaluate sleep quality (Pittsburgh Sleep Quality Index, PSQI), insomnia severity (Insomnia Severity Index, ISI), psychological distress (Clinical Outcomes in Routine Evaluation–Outcome Measure, CORE-OM) and additionally impact of fatigue (Modified Fatigue Impact Scale, MFIS) after 8-weeks. Results: Insomnia severity measured with ISI (F(1;22)=5.95, p = 0.023, η p 2 = 0.213, 90% CI = 0.02–0.42) and psychological distress measured with the CORE-OM (F(1;22)=4.82, p = 0.039, η p 2 = 0.179, 90% CI = 0.01–0.40) showed statistically significant group-by-time interaction. Sleep quality measured with the PSQI showed statistically significant group-by-time interaction only in an aspect of daytime sleep dysfunction (F(1;22)=5.33, p = 0.031, η p 2 = 0.195, 90% CI = 0.01–0.40). The fatigue impact measured with the MFIS showed statistically significant group-by-time interaction in physical (F(1;22)=6.80, p = 0.016, η p 2 = 0.236, 90% CI = 0.02–0.44) and cognitive aspects (F(1;22)=9.12, p = 0.006, η p 2 = 0.293, 90% CI = 0.05–0.49), and total score (F(1;22)=11.29, p = 0.003, η p 2 = 0.339, 90% CI = 0.08–0.52). Conclusions: Our 8-week program reduced insomnia severity, psychological distress and some aspects of fatigue (physical; cognitive; total), and improved sleep quality in an aspect of daytime sleep dysfunction in a small group of individuals with MS. Good feasibility and significant positive changes from baseline warrant further exploratory work.

Osteopontin (OPN), an extracellular matrix (ECM) glyco-phosphoprotein, plays an important role in autoimmune-mediated demyelinating diseases, including multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). As an integrin and CD44 binding protein it participates in bidirectional communication between the ECM and target cells and affects transduction pathways that maintain neuronal and immune cell homeostasis. Its biological activity is also heavily influenced by microenvironment, which stimulates the cleavage of OPN and changes its functions. In this study we estimated the expression profile of OPN in neural tissues of DA rats during the first relapse of chronic relapsing EAE and investigated the relationship of OPN to metallothionein I+II (MTs), which play pivotal role in zinc-related cell homeostasis and in protection of CNS against cytokine-induced injury. The data showed that in EAE rats OPN mRNA and protein levels increased concurrently with the transcription of MTs and that within the spinal cord (SC) lysates EAE-afflicted rats had a higher content of OPN fragments of low molecular weight than untreated and CFA-treated rats. The expression of OPN and MTs was upregulated on ependymal, lymphoid and astroglial cells and on multiple αvβ3+ neurons in SC and in the brain (cortex, white matter, hippocampus, and cerebellum). Besides, multiple cells co-expressed OPN and MTs. Granular OPN signals were detected in secretory vesicles of Golgy (αvβ3 neurons) and in patches adjacent to the plasma membrane (subventricular zone). The findings imply that in demyelinating lesions are generated proteolytic OPN fragments and that OPN/MT interactions contribute to tissue remodeling during an autoimmune attack.