Continuous exposure of many types of neurons in cell culture to elevated concentrations of K+ greatly enhances their survival. This effect has been reported to be mediated by a sustained rise of cytoplasmic free Ca*+ concentration caused by influx of Ca2+ through voltage-gated channels activated by K+-induced chronic depolarization. In this report we investigate the effects of elevated K+ on the programmed death that embryonic rat sympathetic neurons undergo in culture when deprived of NGF. Elevated K+ in the culture medium did not significantly prevent death of NGF-deprived cells until after the third day following plating of embryonic day 21 neurons. On the fifth day after plating, incrementally increasing K+ concentrations in the culture medium from 5 to 100 mu caused chronic depolarization of neurons and had a biphasic effect on survival of NGF-deprived cells. Enhanced survival was steeply related to membrane potential, increasing from no enhanced survival in cells held at potentials between-51 and-34 mV to 90-100% of control survival at about-21 mV. At potentials positive to-21 mV, survival decreased. Associated with the chronic depolarization was a sustained rise of steady-state free Ca2+ concentration that showed a biphasic relationship to membrane potential roughly similar to that exhibited by survival. Steadystate Ca*+ concentration increased with increasingly lower membrane potentials to a peak at about-23 mV (to ~240 nu from ~40 nM at about-51 mV) and then decreased at more positive potentials. The elevation of intracellular Ca2+ was largely blocked by dihydropyridine and phenylalkylamine Ca2+ channel antagonists and was potentiated by a dihydropyridine Ca2+ channel agonist. Neither the rise of Ca*+, or survival was affected by the CaZ+ channel antagonist, o-conotoxin. Therefore, the Ca*+ elevation was probably caused by Ca*+ influx through L-type, but not N-type, chan

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Several biomarkers are used in confirming the diagnosis of cognitive disorders. This study evaluates whether the level of these markers after heart surgery correlates with the development of cognitive dysfunction, which is a frequent complication of cardiac interventions. Concentrations of amyloid-β peptide, tau, and S100β in the cerebro-spinal fluid were assessed, as well as cognitive functions were evaluated before and after coronary artery bypass grafting, utilizing immuno-assays and psychometric tests, respectively. A drastic rise in the level of S100β was observed one week after the surgery, a mark of a severe generalized cerebral injury. The level of amyloid-β peptide significantly decreased, whereas the concentration of tau markedly increased six months postoperatively. Gradual cognitive decline was also present. These findings clearly demonstrate post-surgical cognitive impairment associated with changes in biomarkers similar to that seen in Alzheimer's disease, suggesting a unifying pathognomic factor between the two disorders. A holistic approach to coronary heart disease and Alzheimer's-type dementia is proposed.

Molecular components of the dopaminergic system may play an important role in the pathophysiology of schizophrenia. In this study, we investigated the relationship of the Ser9Gly (S/G) polymorphism of the dopamine D3 receptor (DRD3) and the variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) with therapeutic response to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) and cognitive functions. No associations were found between the DRD3 and DAT polymorphisms and schizophrenia. The S/S genotype and the S allele were more frequent in the non-responder patients (n = 28) than in the group of responders (n = 47) (cut-off: >20-point improvement in Global Assessment of Functioning (GAF) scale). The patients with S/S genotype completed fewer categories and had more perseverative errors in the Wisconsin Card Sorting Test (WCST) compared with the S/G patients. The S/S and S/G patients did not differ in positive and negative symptoms, GAF scores, WCST failure to maintain set, and verbal learning. No differences in symptoms or WCST measures were observed in the patients with different DAT genotypes. These results suggest that the S/S genotype of the DRD3 is associated with worse therapeutic response and more severe executive dysfunctions in patients with schizophrenia.