GABAergic Neuron Deficit As An Idiopathic Generalized Epilepsy Mechanism: The Role Of BRD2 Haploinsufficiency In Juvenile Myoclonic Epilepsy

Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/− mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/− males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/− female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/− vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/− mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR), yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/− mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i) sex-specific increases in seizure susceptibility, ii) the development of spontaneous seizures, and iii) seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE

Factors of students’ intercultural competence development in the context of Georgia

Research aims to define the impact of diverse cultural factors on formation of students’ intercultural competences. Study revealed following negative tendencies: students have insufficient knowledge about different cultures, in fact, they do not have any experience of communicating with other cultural representatives, and they are reluctant to integrate with different cultures. These gaps are directly correlated with school culture dimensions, such as: school community diversity, teaching content, and the style of pedagogical relations. Among the positive trends, we can differentiate the following: students’ readiness to consider different views in school-related decision-making process; students’ belief that they can improve the school culture. The school, as the leading agent of intercultural education, should undertake the responsibility for developing intercultural competencies in students in order to eliminate the identified gaps and strengthen the positive trends, which can be achieved by active, consistent, and purposeful use of intercultural education methods and extracurricular educational strategies

Factors of students' intercultural competence development in the context of Georgia PUBLIC INTEREST STATEMENT

Abstract: Research aims to define the impact of diverse cultural factors on formation of students' intercultural competences. Study revealed following negative tendencies: students have insufficient knowledge about different cultures, in fact, they do not have any experience of communicating with other cultural representatives, and they are reluctant to integrate with different cultures. These gaps are directly correlated with school culture dimensions, such as: school community diversity, teaching content, and the style of pedagogical relations. Among the positive trends, we can differentiate the following: students' readiness to consider different views in school-related decision-making process; students' belief that they can improve the school culture. The school, as the leading agent of intercultural education, should undertake the responsibility for developing intercultural competencies in students in order to eliminate the identified gaps and strengthen the positive trends, which can be achieved by active, consistent, and purposeful use of intercultural education methods and extracurricular educational strategies. PUBLIC INTEREST STATEMENT In Georgia as historically multicultural country, the modern trends of transformation of social, economic, political, demographic, and cultural environment has conditioned the search for adequate educational solutions. This research is an attempt to find solution through studying students' intercultural awareness and the factors affecting it. Intercultural education is directly related with intercultural awareness of family, school, and society. It was found that positive changes in family, school, and society culture towards diversity, parenting, and teaching content, style of relations has its immediate effect of students' intercultural competencies. Understanding these effects can improve future programs for intercultural education. Exploration of intercultural education issues can also help all the interested parties (Ministry of Education and Science, public schools, self-governments, non-government organizations, and parents) to develop and implement successful experience and overcome the difficulties

Susceptibility of <i>Brd2</i> heterozygous KO mice (<i>+/-</i>) and control littermates (+/+) to flurothyl-induced seizures.

<p>Seizure threshold is depicted in µl of flurothyl necessary to induce specific seizure type (Mean±S.E.M.). (A) In females, tonic-clonic seizures in <i>Brd2+/-</i> mice had significantly lower threshold than in <i>Brd2+/+</i> littermate controls. (B) In males, clonic seizures in <i>Brd2+/−</i> mice had significantly lower threshold than in <i>Brd2+/+</i> littermate controls.</p