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The development of atherosclerotic cardiovascular disease is a common comorbidity in patients with the metabolic syndrome, a concurrence of cardiovascular risk factors in one individual. While multiple growth factors and adipokines are identified in atherosclerotic lesions, as well as neurotrophins implicated in both cardiac ischemia and lipid and glucose metabolism, the potential role of neurotrophins in human coronary atherosclerosis and in the metabolic syndrome still remains to be elucidated. Here we describe and discuss our results that represent a novel attempt to study the cardiovascular and metabolic biology of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and mast cells (MC). The local amount of NGF, the immunolocalization of p75 neurotrophin receptor (p75NTR) and the number of MC were correlatively examined in coronary vascular wall and in the surrounding subepicardial adipose tissue, obtained from autopsy cases in humans with advanced coronary atherosclerosis. We also analyzed the plasma levels of NGF, BDNF and leptin and the number of MC in biopsies from abdominal subcutaneous adipose tissue in patients with a severe form of the metabolic syndrome. The results demonstrate that NGF levels are decreased in atherosclerotic coronary vascular tissue but increased in the subepicardial adipose tissue, whereas both tissues express a greater number of MC and a stronger p75NTR immunoreactivity, compared to controls. Metabolic syndrome patients display a significant hyponeurotrophinemia and an increased number of adipose MC; the later correlates with elevated plasma leptin levels. In effect, we provide the first evidence for (i) an altered presence of NGF, p75NTR and MC in both coronary vascular and subepicardial adipose tissue in human coronary atherosclerosis, and (ii) a significant decrease in plasma NGF and BDNF levels and an elevated amount of plasma leptin and adipose MC in metabolic syndrome patients. Together our findings suggest that neuroimmune mediators such as NGF, BDNF, leptin and MC may be involved in the development of cardiovascular disease and related disorders.

In this study we investigate the effects of short-term hypergravity on lung and heart neurotrophins and mast cell distribution. Our results showed that brain derived-neurotrophic factor (BDNF) protein and mRNA expression are increased in the lungs of mice exposed to hypergravity while in the heart hypergravity causes a marked reduction in BDNF mRNA expression, and a decrease in BDNF protein. Compared to controls, nerve growth factor (NGF) protein was expressed more in the heart of rotated mice. These observations demonstrate that altered hypergravity can affect, though differentially, the local expression of NGF and BDNF proteins and their mRNAs in the lung and heart and indicates that short-term exposure to hypergravity causes a marked increase in BDNF, but not in NGF in the lungs of adult mice. Moreover, mast cells, which are NGF-producing cells and implicated in cardiac and respiratory activity, increased in number in proximity to blood vessels in the heart and in lung airway epithelium of rotated mice. This study indicates that hypergravity influences cardiovascular and respiratory tissue and suggests a neurotrophin involvement in the reaction to this environmental exposure.

Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are members of a family of structurally related secreted proteins, termed neurotrophins, which promote and regulate the survival of many kinds of neurons in the peripheral nervous system. Aim of the study is to dose the serum level of NGF and BDNF in 8 patients affected by sensorineural hearing loss (SNHL). The results show that in these patients the amount of circulating NGF, but not of BDNF, is significantly lower in comparison to that found in age-matched controls. The preliminary data of the present study suggest that NGF might have a crucial role in the auditory pathway, promoting the survival and preventing the degeneration of sensorineural cells.

We previously reported that prenatal methylazoxymethanol (MAM) administered on days 11 and 12 of rat pregnancy induces structural changes in the cytoarchitecture of the hippocampal-entorhinal axis. We also showed that young and middle-aged prenatally treated MAM animals displayed changes in brain neurotrophin levels [Neurosci. Lett. 309 (2001) 113; Physiol. Behav. 71 (2000) 57.]. To continue this line of investigation, the working hypothesis adopted was that prenatal MAM administration, by interfering with limbic neurogenesis, could impair learning and memory ability of aged animals in the water maze. It was found that injection of MAM during early rat brain development induced deficits in both the acquisition and retention phases of the Morris maze. These behavioral changes were associated with significant changes in brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), reduced choline acetyltransferase (ChAT) immunoreactivity in forebrain cholinergic neurons and loss of neuropeptide Y (NPY) immunodistribution in cells of the entorhinal cortex. This finding, as well as confirming previous studies showing that injection of prenatal MAM administration induces significant changes in hippocampal-entorhinal axis neurogenesis and marked behavioral deficits in adult life, provides additional experimental evidence supporting the hypothesis that loss of NGF and/or BDNF-receptive or producing cells can co-occur at the onset of neurodevelopmental disorders.