Animal models of epilepsy are essential for the search of new effective antiepileptic drugs. Moreover they may lead to the discovery of the basic neuronal dysfunction(s) which underlies human epilepsies. Animal epilepsies as well as experimental seizures are usually considered as valid models of human epilepsies when, and only when, the drugs which are effective in human epilepsies prevent seizures in animals. This, however, precludes finding new drugs for resistant epilepsies. Animal models of epilepsy can be classified as follows: (i) experimental seizures induced by convulsant drugs or by an electrical stimulation; (ii) reflex epilepsies; (iii) idiopathic epilepsies. Examples of animal models of epilepsy taken from each of these three classes are briefly reviewed. Seizures induced by convulsant drugs or by an electroshock are widely used as simple and rapid screening systems for new anticonvulsant compounds. Moreover, the use of chemical convulsants can lead to new hypotheses concerning the mechanisms underlying human epilepsies. Thus, one of the main arguments in favor of the GABAergic hypothesis of epilepsy is that GABA antagonists induce seizures which are readily counteracted by most antiepileptic drugs. Among the other models of experimentally induced seizures, the kindling model is usually considered, on the basis of its pharmacological characteristics, as a Grand Mal type epilepsy model. Thirty years after this model was first described, the exact modifications induced in the brain by the kindling procedure remain unknown. Various animal species exhibit reflex epilepsies. Myoclonic seizures can be induced by photic stimulation in Papio-papio baboons; tonic-clonic seizures can be induced by various auditory stimuli in certain strains of mice and rats; myoclonic and tonic-clonic seizures can be induced by a variety of environmental stimuli in the mongolian gerbil; photosensitive and febrile seizures have been described in fowl. Most antiepileptic drugs are effective in these reflex epilepsies. Alterations in several neurotransmitter systems have been reported in susceptible strains as compared to resistant strains, such as modifications in noradrenergic, serotoninergic, GABAergic or glutamatergic transmissions, but no single abnormal parameter can unequivocally be correlated to seizure susceptibility. Idiopathic epilepsy is not uncommon in dogs and the prevalence of the disease appears to be comparable to that observed in man. Grand Mal type epilepsy appears to be the most frequent type of epilepsy in dogs; little work has been devoted to the study of the neurochemical alterations which may underly the disease.
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Mol Biol Cell
January 2025
Department of Cell Biology, Emory University, 615 Michael St, Atlanta, GA, USA, 30322.
Rare inherited diseases caused by mutations in the copper transporters (CTR1) or induce copper deficiency in the brain, causing seizures and neurodegeneration in infancy through poorly understood mechanisms. Here, we used multiple model systems to characterize the molecular mechanisms by which neuronal cells respond to copper deficiency. Targeted deletion of CTR1 in neuroblastoma cells produced copper deficiency that produced a metabolic shift favoring glycolysis over oxidative phosphorylation.
View Article and Find Full Text PDFEpileptic Disord
January 2025
Child Neurology and Psychiatry Unit, Dipartimento materno-infantile, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Hum Mol Genet
January 2025
Department of Cell & Developmental Biology, Vanderbilt University School of Medicine, 1161 21st Ave S, Nashville, Tennessee, 37232, United States of America.
Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. While benign tumors in the heart, lungs, kidney, and brain are all hallmarks of the disease, the most severe symptoms of TSC are often neurological, including seizures, autism, psychiatric disorders, and intellectual disabilities. TSC is caused by loss of function mutations in the TSC1 or TSC2 genes and consequent dysregulation of signaling via mechanistic Target of Rapamycin Complex 1 (mTORC1).
View Article and Find Full Text PDFThe hippocampus forms memories of our experiences by registering processed sensory information in coactive populations of excitatory principal cells or ensembles. Fast-spiking parvalbumin-expressing inhibitory neurons (PV INs) in the dentate gyrus (DG)-CA3/CA2 circuit contribute to memory encoding by exerting precise temporal control of excitatory principal cell activity through mossy fiber-dependent feed-forward inhibition. PV INs respond to input-specific information by coordinating changes in their intrinsic excitability, input-output synaptic-connectivity, synaptic-physiology and synaptic-plasticity, referred to here as experience-dependent PV IN plasticity, to influence hippocampal functions.
View Article and Find Full Text PDFFront Cell Neurosci
January 2025
Hainan General Hospital and Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Protein lactylation is a new form of post-translational modification that has recently been proposed. Lactoyl groups, derived mainly from the glycolytic product lactate, have been linked to protein lactylation in brain tissue, which has been shown to correlate with increased neuronal excitability. Ischemic stroke may promote neuronal glycolysis, leading to lactate accumulation in brain tissue.
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