Anti-GABRB2 (internal region) polyclonal antibody

Chronic agonistic interactions lead to the development of pathology of aggressive behavior in winning male mice and mixed anxiety/depression-like state in defeated one. These psychoemotional states are accompanied by altered motor behaviors. The paper aimed to study the movement disturbances in male mice with use of CatWalk XT instrument (Noldus IT, Wageningen, the Netherlands). As parameters of altered neurotransmitter regulation we have analyzed expression of genes encoding proteins related with the metabolism and receptors of catecholaminergic, GABAergic and glutamatergic systems in the dorsal striatum which is important in the regulation of motor behaviors. Disturbances in motor activity in male mice were generated by exposure to repeated agonistic interactions using the sensory contact model [Kudryavtseva, 1991]. The collected samples of the dorsal striatum were sequenced at JSC Genoanalytica (http://genoanalytica.ru/, Moscow, Russia). Different disturbances of gait and impaired coordination in both aggressive and depressive male mice were shown. In the striatum of depressive mice there were found: decreased expression of catecholaminergic genes - Comt, Drd1, Drd2, Snca, Adra2c and increased expression of Sncb, Slc6a3 Adra2a, Adra1b, Adrbk1, Adrbk; increased expression of glutamatergic Grm1, Grm2, Slc17a6, Slc17a7, Grin2c, Grik1, Grid2ip genes. GABAergic Gabbr2 and Gabrb2 genes were upregulated, and Gabra2 gene was downregulated. In aggressive mice the expression of catecholaminergic Drd4, Slc17a7 genes were increased and Th gene was decreased. GABAergic Gabra2, Gabra3, Gabrb2, Gabrg2, Gabrg3 genes were downregulated. It is suggested that the leading role in psychomotor disturbances in aggressive mice plays decreased inhibitor control of GABAergic system, and in depressive mice - activation of glutamatergic system. Dopaminergic activity is decreased in both social groups with long experience of agonistic interactions.

Aim To characterize the different phenotypes ofGABRB2-related epilepsy and to establish a genotype-phenotype correlation. Method We used next-generation sequencing to identifyGABRB2variants in 15 patients. Results ElevenGABRB2variants were novel and 12 were de novo. The age at the onset of seizures ranged from 1 day to 26 months. Nine patients had multiple seizure types, including focal seizures, generalized tonic-clonic seizures, myoclonic seizures, epileptic spasms, and atonic seizures. Seizures were fever-sensitive in 13 out of the 15 patients. Eleven patients displayed developmental delay, while 11 had abnormal video electroencephalography. Abnormalities in the brain images included dysplasia of the frontal and temporal cortex, dysplasia of the corpus callosum, and delayed myelination in four patients. One patient was diagnosed with febrile seizures, three with febrile seizures plus, three with Dravet syndrome, three with West syndrome, one with Ohtahara syndrome, three with developmental delays and epilepsy, and one with non-specific early-onset epileptic encephalopathy. Interpretation The most common phenotypes of patients withGABRB2variants include early onset of seizure and fever sensitivity. Febrile seizures and febrile seizures plus are new phenotypes ofGABRB2variants. The phenotypic spectrum ofGABRB2variants ranges from mild febrile seizures to severe epileptic encephalopathy.