The endozepine mystery

Compound unknown. GABA is the main inhibitory neurotransmitter in the Central Nervous System and its effect is mediated through GABA receptors. Benzodiazepines are compounds that reinforce the action of GABA in the brain, which gives them antiepileptic properties. Consequently, benzodiazepines are one of the most common groups of antiepileptic drugs used to interrupt acute epileptic seizures. Interestingly, benzodiazepines have their own binding site on the GABA receptor, suggesting that they might actually mimic the effect of another, yet unknown substance that is present in the brain. The identity of this mysterious substance, the endogenous benzodiazepine or endozepine, has been one the romantic mysteries of neuroscience. Now, a recent paper in Neuron provides strong evidence that products of the DBI gene are the long-sought endozepine. Continue reading

NRXN1 deletions and the double hit hypothesis of idiopathic epilepsy

Old friends. Structural genomic variants or Copy Number Variations (CNVs) play an important role in many neurodevelopmental disorders including epilepsy, autism, schizophrenia and intellectual disability. Many of the CNVs representing genetic risk factors overlap between these diseases. Now, a recent study in Epilepsia reports on the exon-disrupting deletions in NRXN1 as genetic risk factors for Idiopathic Generalised Epilepsy. NRNX1 deletions were previously reported in several other neurodevelopmental disorders. However, there is an interesting and unanticipated twist to the story. Continue reading