Cardiovascular psychiatry and neurology最新文献

The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30-40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4-8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

Adipocytes contain high levels of S100B and in vitro assays indicate a modulated secretion of this protein by hormones that regulate lipolysis, such as glucagon, adrenaline, and insulin. A connection between lipolysis and S100B release has been proposed but definitive evidence is lacking. Although the biological significance of extracellular S100B from adipose tissue is still unclear, it is likely that this tissue might be an important source of serum S100B in situations related, or not, to brain damage. Current knowledge does not preclude the use of this protein in serum as a marker of brain injury or astroglial activation, but caution is recommended when discussing the significance of changes in serum levels where S100B may function as an adipokine, a neurotrophic cytokine, or an alarmin.

Increasing evidence suggests that the small EF-hand calcium-binding protein S100B plays an important role in Alzheimer's disease. Among other evidences are the increased levels of both S100B and its receptor, the Receptor for Advanced Glycation Endproducts (RAGEs) in the AD diseased brain. The regulation of RAGE signaling by S100B is complex and probably involves other ligands including the amyloid beta peptide (Abeta), the Advanced Glycation Endproducts (AGEs), or transtheyretin. In this paper we discuss the current literature regarding the role of S100B/RAGE activation in Alzheimer's disease.

It has recently been suggested that mood disorders can be characterized by glial pathology as indicated by histopathological postmortem findings. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. This protein might act as a growth and differentiation factor. It is located in, and may actively be released by, astro- and oligodendrocytes. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Successful antidepressive treatment reduces S100B in major depression whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered. By indicating glial alterations without neuronal changes, serum S100B studies confirm specific glial pathology in mood disorders in vivo. S100B can be regarded as a potential diagnostic biomarker for mood disorders and as a biomarker for successful antidepressive treatment.

Growing evidence is now available on the use of S100B protein as a valuable marker of brain damage and its role as a neurotrophic factor. Bearing in mind, among different S100B protein properties that are still being investigated, the possibility of measuring this protein in different biological fluids renders it suitable for use in several disciplines. This is the case with perinatal medicine where even more noninvasive techniques are particularly desirable in order to ensure the minimal handling diagnostic and therapeutic strategies. In this setting, the present minireview reports data on the presence and the usefulness of S100B protein as brain damage marker and as a neurotrophic factor in the so-called unconventional biological fluids such as saliva and human milk, respectively. Results offer new possibilities for the use of S100B in perinatal medicine as a key-protein for the investigations focusing on central nervous system development and damage.

Serotonin transporter clustering is an important feature for regulation of this transporter activity. We used immunocytochemistry to analyze alterations in serotonin transporter clustering in blood lymphocytes of reeler mice. Serotonin transporter immunolabelling is observed mostly as a patchy staining in lymphocytes membranes. Comparison of the number and size of serotonin transporter clusters in wild-type mice, heterozygous reeler mice, and homozygous reeler mice showed an increase in the number and size of clusters in heterozygous reeler mice, but only an increase in clusters size in homozygous reeler mice. Reelin is down-regulated in the brain of schizophrenia, autism, and mood disorders, and is also expressed in blood plasma. There is the possibility therefore that alterations in serotonin transporter clustering in blood lymphocytes associated with a decrease in reelin expression may be operative in some cardiovascular or immune system alterations showing comorbidity with these mental disorders.

S100B is an EF-hand calcium-binding protein that exerts both intracellular and extracellular effects on a variety of cellular processes. The protein is predominantly expressed in the central nervous system by astrocytes, both physiologically and during the course of neurological disease. In the healthy adult brain and during development, constitutive S100B expression acts as a trophic factor to drive neurite extension and to referee neuroplasticity. Yet, when induced during central nervous system disease, the protein can take on maladaptive roles and thereby exacerbate brain pathology. Based on genetic and pharmacological lines of evidence, we consider such deleterious roles of S100B in two common brain pathologies: ischemic stroke and Alzheimer's disease (AD). In rodent models of ischemic brain damage, S100B is induced early on during the subacute phase, where it exacerbates gliosis and delayed infarct expansion and thereby worsens functional recovery. In mouse models of AD, S100B drives brain inflammation and gliosis that accelerate cerebral amyloidosis. Pharmacological inhibition of S100B synthesis mitigates hallmark pathologies of both brain diseases, opening the door for translational approaches to treat these devastating neurological disorders.

Objective. Depression has been found to be an independent risk factor with cardiovascular diseases (CVDs) and also associated with increased mortality among these patients. Method. We used a comprehensive database of all suicides (n = 2, 283) committed in Northern Finland with information on all hospital-treated cardiovascular diseases and psychiatric disorders. Results. Coronary artery disease (CAD) had been present in 7.7% and other cardiovascular diseases (CVDs) in 11.6% of the suiciders. The likelihood of suicide for patients with hospital-treated CAD was estimated to be two-fold compared to the general population while likelihood for suicide was not elevated among those with other CVDs. Males with CAD and females with CAD or any CVD had been hospitalized significantly more often with depression compared to reference group. Conclusions. Suicidality among patients with cardiovascular diseases has been suggested to associate with depression. Psychiatric consultation is highly recommended in clinical practice for cardiac patients with depression or alcohol-related disorders.

S100B, a calcium-binding protein of the EF-hand type, exerts both intracellular and extracellular functions. S100B is induced in the myocardium of human subjects and an experimental rat model following myocardial infarction. Forced expression of S100B in neonatal rat myocyte cultures and high level expression of S100B in transgenic mice hearts inhibit cardiac hypertrophy and the associated phenotype but augments myocyte apoptosis following myocardial infarction. By contrast, knocking out S100B, augments hypertrophy, decreases apoptosis and preserves cardiac function following myocardial infarction. Expression of S100B in aortic smooth muscle cells inhibits cell proliferation and the vascular response to adrenergic stimulation. S100B induces apoptosis by an extracellular mechanism via interaction with the receptor for advanced glycation end products and activating ERK1/2 and p53 signaling. The intracellular and extracellular roles of S100B are attractive therapeutic targets for the treatment of both cardiac and vascular diseases.