The suprachiasmatic nuclei (SCN) has a rhythm of melatonin and cortisol secretion under the circadian pattern, and then these hormones can feed back into a central oscillator to affect the SCN-dependent rhythms, leading to variable but prominent influence on epilepsy. Clock genes accompanied by two feedback loops of regulation have an important role in cortical excitability and seizure occurrence, which may be involved in the mTORopathy. Sleep influences the epilepsy rhythm, and conversely, epilepsy alters the sleep rhythm through multiple pathways. Apart from the common seizure types, several specific epilepsy syndromes also have a close correlation with sleep-wakefulness patterns. Furthermore, the epilepsy type, seizure type and seizure onset zone can significantly affect the rhythms of seizure occurrence. For instance, specific distribution patterns of seizures and IED have been reported, i.e., lighter non-rapid eye movement (NREM) sleep stage (stage 2) induces seizures while deeper NREM sleep stage (stage 3) activates IEDs. It has been found that sleep-wake patterns, circadian timing systems and multidien rhythms have essential roles in seizure activities and interictal epileptiform discharge (IED). In this review, we present the reciprocal relationship between CR and epileptic activities from aspects of sleep effect, genetic modulation and brain biochemistry. An adequate understanding of how circadian system and epilepsy interact with each other could contribute to more accurate seizure prediction as well as rapid development of potential treatment timed to specific phases of CR. Giraldez emphasized that the mechanism of action of the estrogenic compounds in zebrafish is still unknown and further studies in mice are a critical next step before this work can be applied to humans.Evidence about the interaction between circadian rhythms (CR) and epilepsy has been expanded with the application of advanced detection technology. “This research helps scientists understand the function of an autism risk gene in brain development, which is important for understanding the biology of autism,” Hoffman said. “These compounds did not act like a sedative, rather they reversed the abnormal behavior in a specific manner,” Giraldez said.
They found that drugs that act like estrogens were able to restore normal activity levels at night in the mutant fish.
The team compared the behavior of normal fish exposed to hundreds of approved drugs to the behavior of fish carrying the mutation and predicted which drugs could trigger or suppress the abnormal behavior. Mutations in zebrafish cntnap2 result in a loss of inhibitory neurons in the developing brain and cause the fish to become hyperactive at night, they found. The team studied the effect of disrupting this gene in zebrafish, which are transparent and allow scientists to visualize key processes during brain development. A mutation in this gene in some Amish families has previously been shown to cause a form of autism and epilepsy. The research team led by Ellen Hoffman, assistant professor at the Yale Child Study Center, along with Giraldez, Matthew State at the University of California-San Francisco, and Jason Rihel at University College London - focused on the gene CNTNAP2. “Our study shows the strength of using zebrafish mutants as a platform to identify compounds with relevance to autism, though there is much more work to do before this can be applied to humans.” “We were very surprised by this finding,” said Antonio Giraldez, professor of genetics and co-senior author of the paper. The effect of a female hormone intrigued scientists because autism is four times more common in males than females. Gene expression patterns in a zebrafish with autism risk gene.Ī Yale-led team of scientists found that estrogens could reverse abnormal behavior in zebrafish carrying a mutation in a gene strongly associated with autism and seizures in humans, they reported Jan.
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