The role of neutrophil gelatinase associated lipocalin (NGAL) as biological constituent linking depression and cardiovascular disease.

Depression is more common in patients with cardiovascular disease than in the general population. Conversely, depression is a risk factor for developing cardiovascular disease. Comorbidity of these two pathologies worsens prognosis. Several mechanisms have been indicated in the link between cardiovascular disease and depression, including inflammation. Systemic inflammation can have long-lasting effects on the central nervous system, which could be associated with depression. NGAL is an inflammatory marker and elevated plasma levels are associated with both cardiovascular disease and depression. While patients with depression show elevated NGAL levels, in patients with comorbid heart failure, NGAL levels are significantly higher and associated with depression scores. Systemic inflammation evokes NGAL expression in the brain. This is considered a proinflammatory effect as it is involved in microglia activation and reactive astrocytosis. Animal studies support a direct link between NGAL and depression/anxiety associated behavior. In this review we focus on the role of NGAL in linking depression and cardiovascular disease.

Sex-specific associations between Neutrophil Gelatinase-Associated Lipocalin (NGAL) and cognitive domains in late-life depression.

BACKGROUND: Although it is well established that late-life depression is associated with both systemic low-graded inflammation and cognitive impairment, the relation between inflammation and cognition in depressed older persons is still equivocal. The objective of this study is to examine the association between plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations and cognitive functioning in late-life depression, including the potentially moderating role of sex. METHODS: A total of 369 depressed older persons (≥60 years) from The Netherlands study of Depression in Older persons (NESDO) were included. Four cognitive domains, i.e. verbal memory, processing speed, interference control and attention were assessed with three cognitive tests (Stroop test, Wais Digit span test, and Rey's verbal learning test). Multiple linear regression analyses were applied with the four cognitive domains as dependent variables adjusted for confounders. RESULTS: The association between NGAL levels and specific cognitive domains were sex-specific. In women, higher NGAL levels were associated with impaired verbal memory and lower processing speed. In men, higher NGAL levels were associated with worse interference control. Higher NGAL levels were not associated with attention. No sex-specific associations of either high sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6) with cognitive functioning were found. CONCLUSION: This study shows sex-specific association of NGAL with cognitive functioning in late-life depression.

Neutrophil gelatinase-associated lipocalin: a novel inflammatory marker associated with late-life depression.

OBJECTIVE: Systemic low graded inflammation has been identified as a possible biological pathway in late-life depression. Identification of inflammatory markers and their association with characteristics of depression is essential with the aim to improve diagnosis and therapeutic approaches. This study examines the determinants of plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL), which is selectively triggered by TNFα receptor 1 signaling within the central nervous system, and its association with late-life depressive disorder. METHODS: Baseline data were obtained from a well-characterized prospective cohort study of 350 depressed and 129 non-depressed older persons (≥60years). Past 6month diagnosis of major depressive disorder (MDD) according to DSM-IV-TR criteria was assessed with the Composite International Diagnostic Interview (CIDI 2.0). Potential determinants of plasma NGAL included sociodemographic characteristics, lifestyle and psychiatric and physical comorbidity. RESULTS: Plasma NGAL concentrations were significantly associated with age, male gender, smoking and waist circumference. Adjusted for these determinants, depressed patients had significantly higher NGAL plasma levels compared to non-depressed comparison group. Depressed patients who did not meet full criteria for MDD in the month before sampling (partially remitted) had lower plasma NGAL levels compared with those who did. Subjects with a recurrent depression had higher plasma NGAL levels compared to those with a first episode. NGAL levels were neither related with specific symptom profiles of depression nor with antidepressant drug use. CONCLUSION: Adjusted for confounders, NGAL plasma levels are increased in depressed older persons, without any effect of antidepressant medication and age of onset.

Potassium humate inhibits carrageenan-induced paw oedema and a graft-versus-host reaction in rats.

It has been shown in a previous study that brown coal-derived potassium humate is safe and effective in suppressing contact hypersensitivity in rats. In this study the efficacy of potassium humate on other types of inflammation was determined. Preparative TLC followed by mass spectroscopy was used in an attempt to fingerprint the product. The effects of potassium humate, at an oral dose of 60 mg/kg bodyweight, on a delayed type hypersensitivity reaction, a carrageenan-induced inflammation model and an allogeneic graft-versus-host reaction (GVHR) in rats were investigated. Paw oedema was used as a measure of inflammation. It was found that potassium humate had no effect on the delayed type hypersensitivity reaction but significantly inhibited the increase in paw volume of the carrageenan-induced oedema in rats which compared favourably with indomethacin treatment. Furthermore, potassium humate inhibited the GVHR induced in normal and cyclophosphamide-treated immune-incompetent rats. The identification of a naturally occurring compound that is safe and effective in reducing different types of inflammation merits further evaluation in clinical trials.