Epilepsy and Behavior | Year: 2016
The experimental finding that a paroxysmal depolarizing shift (PDS), an electrophysiological correlate of seizure activity, is a giant excitatory postsynaptic potential (EPSP) necessitates a mechanism for spatially summating several EPSPs at the level of the postsynaptic terminals (dendritic spines). In this context, we will examine reversible interpostsynaptic functional LINKs (IPLs), a proposed mechanism for inducing first-person virtual internal sensations of higher brain functions concurrent with triggering behavioral motor activity for possible pathological changes that may contribute to seizures. Pathological conditions can trigger a rapid chain generation and propagation of different forms of IPLs leading to seizure generation. A large number of observations made at different levels during both ictal and interictal periods are explained by this mechanism, including the tonic and clonic motor activity, different types of hallucinations, loss of consciousness, gradual worsening of cognitive abilities, a relationship with kindling (which uses an augmented stimulation protocol than that used for inducing long-term potentiation (LTP), which is an electrophysiological correlate of behavioral makers of internal sensation of memory), effect of a ketogenic diet on seizure prevention, dendritic spine loss in seizure disorders, neurodegenerative changes, and associated behavioral changes. The interconnectable nature of these findings is explained as loss of function states of a proposed normal functioning of the nervous system. © 2016 Elsevier Inc. Source
Grunnet M.,Neurosearch |
Grunnet M.,Copenhagen University
Acta Physiologica | Year: 2010
The cardiac action potential can be divided into five distinct phases designated phases 0-4. The exact shape of the action potential comes about primarily as an orchestrated function of ion channels. The present review will give an overview of ion channels involved in generating the cardiac action potential with special emphasis on potassium channels involved in phase 3 repolarization. In humans, these channels are primarily Kv11.1 (hERG1), Kv7.1 (KCNQ1) and Kir2.1 (KCNJ2) being the responsible α-subunits for conducting IKr, IKs and IK1. An account will be given about molecular components, biophysical properties, regulation, interaction with other proteins and involvement in diseases. Both loss and gain of function of these currents are associated with different arrhythmogenic diseases. The second part of this review will therefore elucidate arrhythmias and subsequently focus on newly developed chemical entities having the ability to increase the activity of IKr, I Ks and IK1. An evaluation will be given addressing the possibility that this novel class of compounds have the ability to constitute a new anti-arrhythmic principle. Experimental evidence from in vitro, ex vivo and in vivo settings will be included. Furthermore, conceptual differences between the short QT syndrome and IKr activation will be accounted for. © 2010 Scandinavian Physiological Society. Source
Neurosearch | Date: 2011-01-14
The present application discloses novel 8-aza-bicyclo[3.2.1]oct-3-yloxy)-chromen-2-one derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the application discloses the use of these compounds, a method for therapy and to pharmaceutical compositions comprising these compounds.
Neurosearch | Date: 2010-03-11
The present application discloses novel substituted pyridinyl-methylamine derivatives and their use as modulators of the voltage gated K
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 5.06M | Year: 2009
SyMBaD aims to move forward our knowledge on synapse structure and function in the normal and pathological brain. Brain diseases represent a considerable social and economic burden in Europe. Emerging evidence indicates that synaptic dysfunction is associated with a majority of neurological and psychiatric disorders. Novel therapeutical approaches relie on a better knowledge of the synapse and its pathologies. The network comprises 23 teams from 6 academic centres (Bordeaux, Alicante, Milan, Geneva, Gttingen, Bristol) representing an important fraction of the leading European researchers in the field. Synergies and complementarities between the research teams exist and should develop with the activities of the SyMBaD network. The participants are already well integrated in European scientific collaborative networks, and have an outstanding track-record of training young researchers. Industrial partners (6) will take part as full partners in training by an obligatory placement from 6 to 12 months of 16 ESR among the 26 recruited. The other ESR will be fully integrated into collaborative projects between academic teams. The private sector comprises companies involved in the development of new therapeutical strategies to combat brain diseases (GSK, Neurosearch, Xygen, and Noscira) and companies involved in technical development to be used in synaptic research and beyond (Bioxtal, Amplitude Systems, Explora Nova). The SYMBAD network aims to: Teach a number of increasingly sophisticated techniques required in neuroscience and to advance towards novel therapies. Focus on technological innovation and on interweaving of multilevel approaches. Facilitate future constructive dialogue between academia and industry in the field by involving SMEs in the training of PhD students through collaborative research projects. SyMBaD will make European Neuroscience more attractive to young scientists, it will catalyze multi-level collaborations and foster intersectorial exchanges to advance in the study of some of the foremost Health issues of the European Community.