Antidepressant-like activity of magnesium in the olfactory bulbectomy model is associated with the AMPA/BDNF pathway

Rationale. Numerous studies suggest agents that act on glutamatergic transmission as potential antidepressants. Preclinical and clinical evidence suggests that magnesium, an N-methyl-d-aspartate receptor blocker, may be useful in the treatment of depression. Objective. The aim of this study was to investigate the effects of magnesium on behavior; protein levels of GluN2A, GluN2B [N-methyl-d-aspartate receptor (NMDAR) subunits], GluA1 [α-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid (AMPA) subunit], phospho-Ser-831-GluA1 (P-S831), phospho-Ser-845-GluA1 (P-S845), and brain-derived neurotrophic factor (BDNF); and messenger RNA (mRNA) levels of GluN2A and GluN2B in different brain areas in the olfactory bulbectomy (OB) model of depression in rats. Methods. Magnesium was administered once daily for 14 days at three doses (10, 15, and 20 mg/kg, intraperitoneal) to sham and OB rats. Following treatment, open field and passive avoidance tests were performed in the sham and OB rats. After 24 h, the hippocampus, the prefrontal cortex (PFC), and the amygdala of rats treated with the most active dose (15 mg/kg) were harvested, and the protein and mRNA levels were determined. Results. Chronic administration of magnesium (15 and 20 mg/kg) reduced the number of trials required to learn passive avoidance and reduced the OB-induced hyperactivity. OB increased the P-S845 level in the hippocampus, which was reduced by magnesium treatment. Magnesium significantly increased the levels of BDNF, GluN2B, P-S831, and P-S845 protein (and mRNA) primarily in the PFC and the hippocampus in OB rats. Conclusion. For the first time, the present results demonstrate the antidepressant-like activity of magnesium in the OB animal model of depression and indicate the potential involvement of the AMPA/BDNF pathway in this activity

Chronic treatment with zinc and antidepressants induces enhancement of presynaptic/extracellular zinc concentration in the rat prefrontal cortex

Zinc exhibits antidepressant-like activity in preclinical tests/models. Moreover, zinc homeostasis is implicated in the pathophysiology of affective disorders. The aim of the present study was to examine the effect of chronic zinc, citalopram and imipramine intraperitoneal administration on the presynaptic and extracellular zinc concentration in the rat prefrontal cortex and hippocampus. We used two methods: zinc–selenium histochemistry (which images the pool of presynaptic-vesicle zinc) and anodic stripping voltammetry (ASV) for zinc determination in microdialysate (which assays the extracellular zinc concentration). We report that chronic (14×) zinc (hydroaspartate, 10 and 65 mg/kg) and citalopram (20 mg/kg) administration increased the pool of presynaptic zinc (by 34, 50 and 37%, respectively) in the rat prefrontal cortex. The 21% increase induced by imipramine (20 mg/kg) was marginally significant. Likewise, zinc (hydroaspartate, 65 mg/kg), citalopram and imipramine increased the extracellular zinc (although with a different pattern: time point, area under the curve and/or basal level) in this brain region. Furthermore, zinc induced an increase in presynaptic (by 65%) and extracellular zinc (by 90%) in the hippocampus, while both citalopram and imipramine did not. These results indicate that all of the treatments increase presynaptic/extracellular zinc concentrations in the rat prefrontal cortex, which may then contribute to their antidepressant mechanisms. Alterations induced by zinc (but not antidepressants) administration in the hippocampus may be related to specific zinc mechanisms. All the data (previous and present) on the effect of antidepressant treatments on the presynaptic/extracellular zinc concentrations suggest the involvement of this biometal presynaptic/synaptic homeostasis in the antidepressant mechanism(s)

Secondary hyperparathyroidism in chronic kidney disease: pathomechanism and current treatment possibilities

Secondary hyperparathyroidism (SHPT) is one of the most common metabolic complications resulting from chronic kidney disease (CKD). The complexity of calcium and phosphate disorders associated with CKD is defined by the Kidney Disease Improvement Global Outcomes (KDIGO) working group as CKD-related mineral and bone disorders (CKD-MBD). The last update of the KDIGO guidelines on the conduct in CKD-MBD was published in 2017. The treatment of SHPT is based on 2 strategies: counteracting hyperphosphataemia and suppressing parathyroid hormone (PTH) secretion. Therapy should be based on optimally selected drugs, taking into account additional effects to reduce the risk of chronic complications and side effects. The creation of new drugs with a better safety profile, significant reduction of side effects, and greater efficiency in achieving target serum phosphorus and PTH values forces the gradual replacement of existing treatment with new pharmacotherapies. The aim of this study is to discuss the latest issues (in connection with the latest KDIGO guidelines) regarding the pathomechanism of secondary hyperparathyroidism and the current directions of the therapy in these disorders

Study of the serum copper levels in patients with major depressive disorder

Copper may be involved in the pathophysiology of depression. Clinical data on this issue are very limited and not conclusive. The purpose of the study was to determine the copper concentration in the serum of patients with major depressive disorder and to discuss its potential clinical usefulness as a biomarker of the disease. A case–control clinical study included 69 patients with current depressive episode, 45 patients in remission and 50 healthy volunteers. Cu concentration was measured by electrothermal atomic absorption spectrometry (ETAAS). The mean serum copper level in depressed patients was slightly lower (by 11 %; not statistically significant) than in the control group. Furthermore, there was no significant difference in Cu(2+) concentration between depressive episode and remission, nor between remission and control group. In the remission group were observed significant correlations between copper levels and the average number of relapses over the past years or time of remission. There was no correlation between serum copper and severity of depression, as measured by HDRS and MADRS. The obtained results showed no significant differences between the copper concentration in the blood serum of patients (both with current depressive episode and in remission) and healthy volunteers, as well as the lack of correlations between the copper level in the active stage of the disease and clinical features of the population. Our study is the first conducted on such a large population of patients, so the results may be particularly important and reliable source of knowledge about the potential role of copper in depression

The serum magnesium concentration as a potential state marker in patients with unipolar affective disorder

Aim. The growing body of evidence suggests that magnesium levels can serve as a marker of major depressive disorder (MDD), but findings from clinical trials remain inconclusive. The aim of the presented study was to determine the magnesium concentration in serum of patients with MDD (in the active stage of the disease or in remission) and to analyze the role of magnesium levels as a potential marker of the disease. Methods. Sixty-nine patients with current depressive episode, 45 patients in remission and 50 healthy volunteers were enrolled into the case-control study. The magnesium concentration was measured by flame atomic absorption spectrometry (FAAS). Results. The mean serum magnesium concentration of patients in the depressed phase was significantly higher, compared to the control group. Moreover, magnesium levels of patients in the remission were not significantly different from the concentrations recorded in the healthy volunteers. There was also a positive correlation between the magnesium levels and the severity of depression measured by the Hamilton Rating Scale for Depression (HDRS) and the Montgomery-Asberg Depression Rating Scale (MADRS). Conclusions. The obtained results may suggest a role of magnesium as a state marker reflecting the pathophysiological changes underlying MDD and accompanying severe depressive episodes

The serum concentration of magnesium as a potential state marker in patients with diagnosis of bipolar disorder

Aim. Few scientific reports indicate changes in the concentration of magnesium in the blood of patients with bipolar disorder (BD). So far very little studies concerning these issues have been conducted. Therefore, the aim of this study was to evaluate the serum magnesium level in patients with bipolar disorder (in different phases of the disease) in comparison to healthy volunteers. Methodology. The study included 129 patients (58 subjects in depressive episode, 23 in manic episode and 48 patients in remission) with the diagnosis of bipolar disorder type I or II. The control group consisted of 50 healthy people. Magnesium concentration was measured using flame atomic absorption spectrometry (FAAS). Results. Patients with a current depressive or manic/hypomanic episode had statistically significantly elevated serum magnesium levels compared to healthy volunteers. Moreover, a positive correlation between the duration of the manic/hypomanic episode and the relapse frequency in the last year was observed. The concentration of magnesium in patients in remission was unchanged in relation to the control group. Conclusions. Presented findings suggest a role of serum magnesium level as a potential state marker, reflecting the pathophysiological changes associated with acute episodes of bipolar disorder

Zinc and copper concentration do not differentiate bipolar disorder from major depressive disorder

Aim. The aim of this study was to compare the zinc and copper concentration in the group of patients with bipolar disorder (BD) and major depressive disorder (MDD). Method. 110 patients with the diagnosis of BD and 114 with MDD were qualified to the study. To assess the levels of microelements, the flame atomic absorption spectrometry (FAAS) was used in the case of zinc and the electrothermal atomic absorption spectrometry (ET AAS) was used in the case of copper. Results. There were no differences between concentration of zinc and copper in remission and depressive phase between patients with BD and MDD. Additionally, there were also no statistically significant differences in comparisons including type I and II, early or late phase of BD and MDD. Conclusions. The lack of differences in zinc and copper concentrations between patients with bipolar disorder and major depressive disorder might indicate that those disorders have similar etiology

The serum concentration of copper in bipolar disorder

Aim. Some scientific reports indicate the changes in the concentration of serum copper in patients with bipolar disorder (BD), however the data are inconclusive. The aim of this study was to assess the concentration of copper in the blood serum of patients in various phases of BD compared to healthy volunteers, taking into consideration the specific clinical features, and the stage of illness. Methods. The study enrolled 133 patients with a diagnosis of BD (type I, II and NOS), including 61 people in depressive episode, 23 in mania or hypomania and 49 in remission. The control group consisted of 50 people. Atomic absorption spectrometry was used to measure the concentration of copper. Results. There were no statistically significant differences in the serum copper concentration between patients in various phases of BD (mania/hypomania, depression, remission), sub-types (Type I, Type II + NOS) or stages and healthy volunteers. However, serum copper concentrations in patients in stage 1 was significantly higher than in advanced stages (2+3+4), (β = 0.22; p = 0.02). Serum copper concentration was also the higher, the later the age of onset was (β = 0.33; p < 0.001), and the lower, the greater the number of illness episodes (β = – 0.23; p = 0.02) (multiple regression model, adj R2 = 0.19, p = 0.0001). Conclusions. The dependencies demonstrated above may reflect pathophysiological processes that occur in the course of BD (e.g., inflammatory response and oxidative stress) with a different intensity depending on its stage