Dementia and neurodegenerative diseases: What is known and what is promising at the cellular and molecular level.

Millions of people worldwide are affected by neurodegenerative diseases and cognitive impairment, which includes dementia, while there are only symptomatic treatments available for this syndrome at present. However, several important prospective drug targets have been identified in recent years that can potentially arrest or even reverse the progression of neurodegenerative diseases. Their natural or synthetic ligands are currently in the experimental stage of drug development.

General anaesthesia-related complications of gut motility with a focus on cholinergic mechanisms, TRP channels and visceral pain.

General anesthesia produces multiple side effects. Notably, it temporarily impairs gastrointestinal motility following surgery and causes the so-called postoperative ileus (POI), a multifactorial and complex condition that develops secondary to neuromuscular failure and mainly affects the small intestine. There are currently limited medication options for POI, reflecting a lack of comprehensive understanding of the mechanisms involved in this complex condition.

Bidirectional TRP/L Type Ca Channel/RyR/BK Molecular and Functional Signaloplex in Vascular Smooth Muscles.

TRP channels are expressed both in vascular myocytes and endothelial cells, but knowledge of their operational mechanisms in vascular tissue is particularly limited. Here, we show for the first time the biphasic contractile reaction with relaxation followed by a contraction in response to TRPV4 agonist, GSK1016790A, in a rat pulmonary artery preconstricted with phenylephrine. Similar responses were observed both with and without endothelium, and these were abolished by the TRPV4 selective blocker, HC067047, confirming the specific role of TRPV4 in vascular myocytes.

Microgeometrical dendritic factors predict electrical decoupling between somatic and dendritic compartments in magnocellular neurosecretory neurons.

It is generally assumed that dendritic release of neuropeptides from magnocellular neurosecretory neurons (MNNs), a critical process involved in homeostatic functions, is an activity-dependent process that requires backpropagating action potentials (APs). Still, growing evidence indicates that dendritic release can occur in the absence of APs, and axonal APs have been shown to fail to evoke dendritic release. These inconsistencies strongly suggest that APs in MNNs may fail to backpropagating into dendrites.

Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes.

Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physical and chemical properties, which makes them interesting biocompatible nanostructured materials for various applications, including in the biomedical field. SWCNTs are not inert carriers of drug molecules, as they may interact with various biological macromolecules, including ion channels. To investigate the mechanisms of the inhibitory effects of SWCNTs on the muscarinic receptor cation current (mI, induced by intracellular GTPγs (200 μM), in isolated mouse ileal myocytes, we have used the patch-clamp method in the whole-cell configuration.

Does the Operation of Mitochondrial ATP-Dependent Potassium Channels Affect the Structural Component of Mitochondrial and Endothelial Dysfunctions in Experimental Parkinsonism?

We have previously demonstrated that the development of oxidative stress in some pathologies can be prevented by activation of the mitochondrial ATP-dependent potassium channel (mitoK). Here we studied the effect of modulation of mitoK on the development of mitochondrial and endothelial dysfunction in the medulla oblongata and myocardium of rats with experimental parkinsonism. It is known that uridine-5'-diphosphate, activator of mitoK, does not penetrate the plasma membrane, but it can be synthesized in cells from exogenous uridine that is delivered into cells by special transport systems.

STATE OF COGNITIVE FUNCTIONS IN CHILDREN WITH PATHOLOGY OF DIGESTIVE ORGANS, WHO LIVE AT RADIOACTIVE CONTAMINATED TERRITORIES OF UKRAINE.

Objective: to study the state of cognitive functions in children who were born and permanently live at radioactive contaminated territories (RCT) with pathology of the upper digestive tract, using pathopsychological testing; to increase the effectiveness of treatment and prophylactic measures aimed at preserving and restoring the health of RCT residents.

Design, Patients And Methods: A randomized blind controlled clinical trial was conducted. There were examined, a total of 90 persons aged 6 to 17 years (35 boys and 55 girls) who were divided into two groups: the control group (I) included 30 persons of the conventional «clean» territories, and the main group (II) - 60 patients with patho- logy of the digestive organs who were born and live at the RCT.

C fullerenes selectively inhibit BK but not K channels in pulmonary artery smooth muscle cells.

Possessing unique physical and chemical properties, C fullerenes are arising as a potential nanotechnological tool that can strongly affect various biological processes. Recent molecular modeling studies have shown that C fullerenes can interact with ion channels, but there is lack of data about possible effects of C molecule on ion channels expressed in smooth muscle cells (SMC). Here we show both computationally and experimentally that water-soluble pristine C fullerene strongly inhibits the large conductance Ca-dependent K (BK), but not voltage-gated K (K) channels in pulmonary artery SMC.

ELECTROLYTE CONTENT IN SALIVA OF CHILDREN WITH DEVIATION IN VEGETATIVE STATUS RESIDING AT RADIOACTIVELY CONTAMINATED TERRITORIES OF UKRAINE AFTER APPLICATION OF INTERMITTENT NORMOBARIC HYPOXIA.

Objective was to determine the content of sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+) elec-trolytes in non-stimulated mixed saliva of children, with disorders of autonomous nervous system (ANS), who wereborn and are permanently residing at radioactive contaminated territories after application of intermittent normo-baric hypoxia (INH) of sanogenic level.Patientes and methods. The children (41 boys and 62 girls) aged 6-17 years were examined.

Glycine receptors are involved in hippocampal neuronal damage caused by oxygen-glucose deficiency.

Glycine receptors (GlyRs) belong to the family of ligand-gated cys-loop receptors and effectuate fast inhibitory neurotransmission in central nervous system (CNS). They are involved in numerous physiological processes, such as movement, respiration, and processing of sensory information, as well as in regulation of neuronal excitability in different brain regions. GlyRs play important role in the maintenance of excitatory/inhibitory balance in the hippocampus and participate in the development of various brain pathologies.

Cooperation of HIF- and NCAM-mediated mechanisms in cell viability of hippocampal cultures after oxygen-glucose deprivation.

Neurodegenerative diseases of different genesis are the result of cellular damages including those caused by oxygen and glucose deficit. Neuronal survival or death in brain pathologies depends on a variety of interrelated molecular mechanisms. A key role in modulation of neuron viability belongs to HIF (hypoxia-inducible factor) and NCAM (neural cell adhesion molecules) signaling pathways.

Efficiency of endothelial dysfunctioncorrection in children residents of radioactively contaminated areas using the method of intermittent normobaric hypoxi therapy.

Unlabelled: Objective is to evaluate the effectiveness of intermittent normobaric hypoxi therapy as the means that can posi tively influence on the different links in the pathogenesis of endothelial dysfunction in children residents of radioactively contaminated areas.

Materials And Methods: Disorders of personal and emotional sphere, symptoms of asthenic vegetative and neurot ic character, the signs of the cardiovascular and respiratory systems, abdominal and dyspeptic syndromes are attrib uted to the clinical signs of endothelial dysfunction. There were determined the biochemical parameters of the con tent of stable metabolites of NO, L arginine, lipid peroxidation, antioxidant enzymes in the blood serum; the indices of cellular and humoral immunity; the instrumental indices of vascular endothelium dependent reaction to occlu sion test, ventilating ability of the lungs, the bioelectric activity of the myocardium.

Endothelial atypical cannabinoid receptor: do we have enough evidence?

Cannabinoids and their synthetic analogues affect a broad range of physiological functions, including cardiovascular variables. Although direct evidence is still missing, the relaxation of a vast range of vascular beds induced by cannabinoids is believed to involve a still unidentified non-CB1 , non-CB2 Gi/o protein-coupled receptor located on endothelial cells, the so called endothelial cannabinoid receptor (eCB receptor). Evidence for the presence of an eCB receptor comes mainly from vascular relaxation studies, which commonly employ pertussis toxin as an indicator for GPCR-mediated signalling.

Genetic predisposition to essential hypertension in children: analysis of 17 single nucleotide polymorphisms.

Study of 17 single nucleotide polymorphisms has been performed to determine the factors of genetic predisposition to essential hypertension. Polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length, allele specific PCR or real-time PCR was used for genotyping of 17 single nucleotide polymorphisms in 14 genes in 145 children with essential hypertension and 144 healthy persons with following complex multivariate statistical analysis. Two single nucleotide polymorphisms--MMP9 (C(-1562) --> T) and NOS3 (Glu298 --> Asp)--rs3918242 and rs1799983--were shown to represent the main independent effects with the highest predictive potential (77.

Expression of TNF-alpha mRNA, but not of TNF-alpha receptors mRNA, is detected in single murine oocyte and decreases during oocyte meiotic maturation: single-cell RT-PCR data.

Background: The present study was conducted to investigate the expression of TNF-alpha and its receptors (types I and II) in both oocytes with germinal vesicle and the first polar body in mice.

Methods: Oocytes with intact germinal vesicle were isolated from mouse ovaries and subjected to in vitro maturation to obtain oocytes forming the first polar body. A reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of TNF-alpha and its receptors at mRNA level.

My first 20 years in neuroscience.

Intriguing facts were obtained in the first electrophysiological investigations (1964) that the action potentials (AP) produced by direct depolarization of the cell membrane in different species of mollusks showed specific relations to changes in external ionic composition. In Helix neurons, the generation of AP was well maintained in sodium-free solutions with high calcium or barium content. The amplitude of the spike overshoot in the case was linearly related to the logarithm of calcium concentration.

Anaesthetic and postanaesthetic effect of isoflurane on the multiple-unit activity of the immature rat hippocampus.

We investigated anesthetic and postanaesthetic effect of isoflurane on the multi-unit activity (MUA) in the CA3 region of immature rat hippocampus. MUA amplitude did not significantly change during application of isoflurane. On the other hand MUA frequency significantly decreased during the anesthesia.

Electrically silent neurons in the substantia gelatinosa of the rat spinal cord.

Substantia gelatinosa (SG) neurons are usually categorized on three main types: tonic, adapting and delayed firing (DFNs), based on characteristic firing response evoked by sustained stimulation. Here, the existence of electrically silent neurons (ESNs, 9.3%) is reported by using patch-clamp recording and confocal microscopy in spinal cord slices from 3-5 weeks-old rats.

The effect of neuraminidase blocker on gabazine-induced seizures in rat hippocampus.

Concentration of neuraminidase (NEU), an enzyme which cleaves negatively charged sialic acids from carbohydrate moieties of the cellular membrane, could vary depending on physiological conditions. Multiple evidences suggest that fluctuations of NEU extracellular concentrations can influence neuronal activity. In the present study we examined the effect of down regulation of endogenous NEU activity on seizure-like activity (SLA) induced by gabazine (specific blocker of inhibitory synaptic transmission) in the hippocampal CA1 pyramidal region of cultured slices.

Signal function of potassium channels--clinical aspects.

Potassium (K+) channels are the most diverse class of ion channels, and are important for regulating neuronal excitability and signaling activity in a variety of ways. They are major determinants of membrane excitability, influencing the resting potential of membranes, wave forms and frequencies of action potentials, and thresholds of excitation. Voltage-gated K+ cannels exist not as independent units merely responding to changes in transmembrane potential but as macromolecular complexes able to integrate a plethora of cellular signals that fine tune channel activities.

Antinociceptive effects of color polarized light in animal with formalin test.

Our recent results show the efficacy of pain suppression by exposure of antinociceptive acupuncture points (APs) to white polarized (P) light. But it is known that white light contains electromagnetic waves of different length (colors) and, possibly, not all of them produce a similar effect. There are no comparative data about analgesic affects of the different colors of P light now.

[Morphophysiologic properties of delayed firing neurons in substantia gelatinosa of the rat spinal cord.

Substantia gelatinosa (SG) neurons of the spinal cord are highly heterogeneous in their morphologic and physiologic properties. Based on characteristic firing response evoked by sustained depolarization, neurons can be categorized on three main types: tonic, adapting and delayed firing (DFNs). Here, properties of DFNs in spinal cord slices from 3-5 weeks-old rats were studied with the use of patch-clamp recording and confocal microscopy.

Mechanism of antiseizure effect of isoflurane in the immature rat hippocampus.

The volatile anesthetic isoflurane is often used in children in the management of refractory status epilepticus. However the mechanism of anticonvulsant action of isoflurane during early brain development is not clear. In this study we explore the role of excitatory and inhibitory conductances in antiseizure effect of isoflurane using combination of whole-cell patch-clamp and extracellular field potential recording techniques on two models of epilepsy in a hippocampal slice preparation from immature rat.