Neuroscience
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Genetic diagnosis of childhood epilepsy is crucial to provide disease-specific treatments. This report describes the genetic landscape of childhood epilepsy revealed by targeted next-generation sequencing panels for epilepsy (TNGSP-E) and whole exome sequencing (WES). In this retrospective cohort study, TNGSP-E and/or WES were applied to identify underlying genetic diagnoses in children seen in a single Pediatric Epilepsy Genetics Clinic. ⋯ Additionally, there might be some treatment implications in 30% of patients with genetic diagnoses including SCN1A, SCN2A, SCN8A, and KCNQ2 associated epilepsies by application of effective anti-epileptic drugs or the ketogenic diet therapy. The high diagnostic yield of clinical molecular genetic investigations and their disease-specific treatment implications highlight the importance of genetic diagnosis in childhood epilepsy. We recommend a stepwise diagnostic algorithm including metabolic investigations for treatable disorders, chromosomal microarray analysis, TNGSP-E, and WES.
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Intrauterine exposure to exercise is beneficial to cognition of the offspring. Although it is advisable to start practicing physical exercise during pregnancy, it is probable that practitioners or sedentary women keep their previous habits during gestation. This study was designed to evaluate the effects of maternal aerobic exercise initiated before and maintained during gestation, or performed in these isolated periods, on cognition and plasticity in the hippocampus of offspring. ⋯ No differences were observed in the BDNF levels among the groups. The maternal pregestational and gestational isolated exercise protocols showed similar effects for offspring plasticity and spatial cognitive ability, while the combined protocol simply improved their spatial learning. Interestingly, only pregestational exercise was able to induce plasticity in the offspring hippocampus associated with modulation of global DNA methylation.
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Most of Parkinson's disease (PD) patients experience gastrointestinal dysfunctions, including gastric hypomotility. The dorsal motor nucleus of the vagus (DMV) modulates the motility of the upper gastrointestinal (GI) tract. Paraquat (P) administration induces Parkinsonism in experimental models, and we have developed recently an environmental model of Parkinsonism in which rats are treated with subthreshold doses of P and lectins (P + L), in both models rats develop reduced gastric motility prodromal to the full extent of motor deficits. ⋯ At baseline, the amplitude of miniature excitatory postsynaptic currents was increased in P + L neurons. No differences in the morphology of DMV neurons were observed. These data indicate that the membrane and synaptic properties of DMV neurons are altered in rodent models of Parkinsonism, in which neurons of 10P and P + L rats demonstrate an increased excitatory transmission, perhaps in an attempt to counteract the paraquat-induced gastric hypomotility.
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Deep brain stimulation of the anterior nucleus of the thalamus has been proposed as novel therapy to treat intractable epilepsy. To optimize this approach, we proposed to study the involvement of this nucleus in a non-human primate model of mesial temporal lobe seizure. Two macaques were implanted with one chronic electrode into the hippocampus allowing to monitor the ictal activity. ⋯ The effects of the chemical neuromodulation of the anterior nucleus on the ictal hippocampal activities were studied and electron microscopy analysis was carried out to study morphological modifications induced in the anterior nucleus of the thalamus. Our results demonstrate that the anterior nucleus of the thalamus is directly involved in the pathophysiology of induced seizures since: (1) Electrophysiological study showed an heterogenous excitation during seizure characterized by the appearance of 2 types of neuronal firing response; (2) chemical neuromodulation of the anterior nucleus of the thalamus changed the severity of seizures; (3) morphological modification of the ultrastructure as well as a reduction of synapse density were observed within the ipsilateral anterior nucleus of the thalamus. This study demonstrates that the anterior nucleus of the thalamus is part of the epileptic network activated during temporal lobe seizures and suggests that this nucleus would be valid target for seizure control using deep brain stimulation.
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Post-traumatic stress disorder (PTSD) is triggered by exposure to traumatic events, but not everyone who experiences trauma develops this disorder. Like humans, PTSD-like symptoms develop in some laboratory rodents (susceptible individuals), while others express less or no symptoms (resilient individuals). Here, considering (i) the putative causal role of fear conditioning in PTSD development and (ii) the involvement of the medial prefrontal cortex (mPFC) in the regulation of conditioned fear response, we tested whether trauma-associated changes in the mPFC may discriminate stress-resilient from stress-susceptible mice. ⋯ Dendrites of Golgi-Cox-stained neurons were analyzed in two parts of the mPFC: the prelimbic (PrL) and infralimbic (IL) areas. In the resilient phenotype, the total number of dendrites decreased in the PrL and increased in the IL; however, it decreased only in the IL in the susceptible phenotype compared to controls. These findings demonstrate that the type of post-trauma morphological changes in the mPFC is associated with susceptibility or resilience to trauma-related symptoms.