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Inhibitory System (inhibitory + system)

Distribution by Scientific Domains
Medical Sciences60%
Life Sciences40%

Selected Abstracts

Impaired M-Current and Neuronal Excitability

EPILEPSIA, Issue 2002
Motohiro Okada
Summary: ,Purpose: Benign familial neonatal convulsions (BFNC), a hereditary epilepsy, occurs specifically in newborns and remits spontaneously after this period. Several mutations of either KCNQ2 or KCNQ3, members of the KCNQ-related K+ -channel (KCNQ-channel) family, were identified as a cause of BFNC. Such mutations impair KCNQ-related M- current, an element of the inhibitory system in the central nervous system (CNS), and therefore are thought to result in neuronal hyperexcitability. Methods: To clarify the pathogenesis of BFNC, this study investigated the effects of the KCNQ channel on propagation of neuronal excitability using a 64-channel multielectrode dish (MED64) system for novel two-dimensional monitoring of evoked field potentials including fiber volley (FV) and field excitatory postsynaptic potential (fEPSP). Results: Dup996, a selective KCNQ-channel inhibitor, did not affect the amplitude of FV or fEPSP, but enhanced the FV and fEPSP propagation. The ,-aminobutyric acid (GABA)A -receptor antagonist, bicuculline, enhanced their propagation, whereas ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/glutamate-receptor antagonist, DNQX, reduced both amplitude and propagation of fEPSP without affecting those of FV. Under the condition of GABAA -receptor blockade by bicuculline, Dup996 enhanced the amplitude of fEPSP and propagation of FV and fEPSP without affecting the amplitude of FV. Dup996 enhanced the stimulating effects of bicuculline on the propagation and amplitude of FV and fEPSP, but it did not affect the inhibiting effects of DNQX. Conclusions: These results suggest that the occurrence of BFNC cannot be produced by KCNQ-channel dysfunction alone but by reciprocal action between impaired KCNQ channel and the other unknown. [source]

Anti-protein S antibodies following a varicella infection: detection, characterization and influence on thrombin generation

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2005
V. REGNAULT
Summary., Postinfectious purpura fulminans is a rare disease. Varicella is one of the precipitating conditions and we recently observed such a case. The 4-year-old child was found to have a severe transient protein S deficiency. By enzyme-linked immunosorbent assay and surface plasmon resonance we first demonstrated that anti-protein S antibodies were present and also transient. Next we characterized the epitopes against which these antibodies were directed and found that they predominantly recognized the N-terminal part of protein S. Finally we showed by thrombography a transient dramatic hypercoagulable state as a result of thrombin being unregulated by the dynamic protein C inhibitory system: in vitro thrombin generation, in response to a low concentration of tissue factor, was almost insensitive to activated protein C up to 25 nmol L,1 on day 4 while it was normally sensitive on day 42. For the first time, we demonstrated a temporal relationship between protein S deficiency, antibodies to protein S and hypercoagulability, thus supporting the pathogenic role of these antibodies. [source]

Homeostatic, circadian, and emotional regulation of sleep

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2005
Clifford B. Saper
Abstract A good night's sleep is one of life's most satisfying experiences, while sleeplessness is stressful and causes cognitive impairment. Yet the mechanisms that regulate the ability to sleep have only recently been subjected to detailed investigation. New studies show that the control of wake and sleep emerges from the interaction of cell groups that cause arousal with other nuclei that induce sleep such as the ventrolateral preoptic nucleus (VLPO). The VLPO inhibits the ascending arousal regions and is in turn inhibited by them, thus forming a mutually inhibitory system resembling what electrical engineers call a "flip-flop switch." This switch may help produce sharp transitions between discrete behavioral states, but it is not necessarily stable. The orexin neurons in the lateral hypothalamus may help stabilize this system by exciting arousal regions during wakefulness, preventing unwanted transitions between wakefulness and sleep. The importance of this stabilizing role is apparent in narcolepsy, in which an absence of the orexin neurons causes numerous, unintended transitions in and out of sleep and allows fragments of REM sleep to intrude into wakefulness. These influences on the sleep/wake system by homeostatic and circadian drives, as well as emotional inputs, are reviewed. Understanding the pathways that underlie the regulation of sleep and wakefulness may provide important insights into how the cognitive and emotional systems interact with basic homeostatic and circadian drives for sleep. J. Comp. Neurol. 493:92,98, 2005. © 2005 Wiley-Liss, Inc. [source]

CLINICAL STUDY: Abnormalities in cortical and transcallosal inhibitory mechanisms in subjects at high risk for alcohol dependence: a TMS study

ADDICTION BIOLOGY, Issue 3-4 2008
Kesavan Muralidharan
ABSTRACT Central nervous system (CNS) hyperexcitability and a resulting state of behavioral undercontrol are thought to underlie the vulnerability to early-onset alcohol dependence (AD). The aim of this study was to explore the differences in the functioning of cortical inhibitory systems, utilizing transcranial magnetic stimulation (TMS), in subjects at high risk (HR) and low risk (LR) for AD and to examine the relationship between CNS inhibition and behavioral undercontrol. Right-handed HR (n = 15) and LR (n = 15) subjects, matched for age, gender, height, weight and education, were assessed for psychopathology and family history of alcoholism using the Semi-Structured Assessment for the Genetics of Alcoholism and the Family Interview for Genetic Studies. Following single-pulse TMS, an electromyogram recorded from the right opponens pollicis muscle was used to measure the silent periods at different stimulus intensities. HR subjects had significantly shorter contralateral and ipsilateral (iSP) silent periods and a relatively higher prevalence of ,absent' iSP. They had significantly higher mean externalizing symptoms scores (ESS) than LR subjects, and there was a significant negative correlation between iSP duration and ESS. These preliminary findings suggest that HR subjects have relative impairments in corticocortical and transcallosal inhibitory mechanisms. The consequent state of CNS hyperexcitability may be etiologically linked to the excess of externalizing behaviors observed in this population, which is thought to be a predisposition to a higher risk of developing early-onset alcoholism. [source]

Chronic neuropathic pain: mechanisms, drug targets and measurement

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2007
Nanna B. Finnerup
Abstract Neuropathic pain is common in many diseases or injuries of the peripheral or central nervous system, and has a substantial impact on quality of life and mood. Lesions of the nervous system may lead to potentially irreversible changes and imbalance between excitatory and inhibitory systems. Preclinical research provides several promising targets for treatment such as sodium and calcium channels, glutamate receptors, monoamines and neurotrophic factors; however, treatment is often insufficient. A mechanism-based treatment approach is suggested to improve treatment. Valid and reliable tools to assess various symptoms and signs in neuropathic pain and knowledge of drug mechanisms are prerequisites for pursuing this approach. The present review summarizes mechanisms of neuropathic pain, targets of currently used drugs, and measures used in neuropathic pain trials. [source]