Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The question whether general tetanus arises from the independent sum of multiple local tetani or results from the actions of the transynaptic tetanus neurotoxin (TeNT) in higher brain centres remains unresolved. Despite the blood-borne dissemination of TeNT from an infected wound, the access to the central nervous system is probably prevented by the blood-brain barrier. However, several long-term sequelae (e.g. autonomic dysfunction, seizures, myoclonus, and sleep disturbances) present after the subsidence of muscle spasms might be indicative of central actions that occur farther away from lower motoneurons. Subsequently, the obvious entry route is the peripheral neurons followed by the transynaptic passage to the brain. We aimed at describing the pathophysiological correlates of TeNT translocation using the oculomotor system as a comprehensive model of cell connectivity and neuronal firing properties. In this study, we report that injection of TeNT into the medial rectus muscle of one eye resulted in bilateral gaze palsy attributed to firing alterations found in the contralaterally projecting abducens internuclear neurons. Functional alterations in the abducens-to-oculomotor internuclear pathway resembled in part the classically described TeNT disinhibition. We confirmed the transynaptic targeted action of TeNT by analysing vesicle-associated membrane protein2 (VAMP2) immunoreactivity (the SNARE protein cleaved by TeNT). VAMP2 immunoreactivity decreased by 94.4% in the oculomotor nucleus (the first synaptic relay) and by 62.1% presynaptic to abducens neurons (the second synaptic relay). These results are the first demonstration of physiological changes in chains of connected neurons that are best explained by the transynaptic action of TeNT on premotor neurons as shown with VAMP2 immunoreactivity which serves as an indicator of TeNT activity.
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PMID:Transynaptic effects of tetanus neurotoxin in the oculomotor system. 1598 57

Epilepsy is characterized by impaired circuit function and a propensity for spontaneous seizures, but how plastic rearrangements within the epileptic focus trigger cortical dysfunction and hyperexcitability is only partly understood. Here we have examined alterations in sensory processing and the underlying biochemical and neuroanatomical changes in tetanus neurotoxin (TeNT)-induced focal epilepsy in mouse visual cortex. We documented persistent epileptiform electrographic discharges and upregulation of GABAergic markers at the completion of TeNT effects. We also found a significant remodeling of the dendritic arbors of pyramidal neurons, with increased dendritic length and branching, and overall reduction in spine density but significant preservation of mushroom, mature spines. Functionally, spontaneous neuronal discharge was increased, visual responses were less reliable, and electrophysiological and behavioural visual acuity was consistently impaired in TeNT-injected mice. These data demonstrate robust, long-term remodeling of both inhibitory and excitatory circuitry associated with specific disturbances of network function in neocortical epilepsy.
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PMID:Altered sensory processing and dendritic remodeling in hyperexcitable visual cortical networks. 2616 22

Epilepsy is characterized by substantial network rearrangements leading to spontaneous seizures and little is known on how an epileptogenic focus impacts on neural activity in the contralateral hemisphere. Here, we used a model of unilateral epilepsy induced by injection of the synaptic blocker tetanus neurotoxin (TeNT) in the mouse primary visual cortex (V1). Local field potential (LFP) signals were simultaneously recorded from both hemispheres of each mouse in acute phase (peak of toxin action) and chronic condition (completion of TeNT effects). To characterize the neural electrical activities the corresponding LFP signals were analyzed with several methods of time series analysis. For the epileptic mice, the spectral analysis showed that TeNT determines a power redistribution among the different neurophysiological bands in both acute and chronic phases. Using linear and nonlinear interdependence measures in both time and frequency domains, it was found in the acute phase that TeNT injection promotes a reduction of the interhemispheric coupling for high frequencies (12-30 Hz) and small time lag (<20 ms), whereas an increase of the coupling is present for low frequencies (0.5-4 Hz) and long time lag (>40 ms). On the other hand, the chronic period is characterized by a partial or complete recovery of the interhemispheric interdependence level. Granger causality test and symbolic transfer entropy indicate a greater driving influence of the TeNT-injected side on activity in the contralateral hemisphere in the chronic phase. Lastly, based on experimental observations, we built a computational model of LFPs to investigate the role of the ipsilateral inhibition and exicitatory interhemispheric connections in the dampening of the interhemispheric coupling. The time evolution of the interhemispheric coupling in such a relevant model of epilepsy has been addressed here.
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PMID:Time evolution of interhemispheric coupling in a model of focal neocortical epilepsy in mice. 2773 54