Project description:Our previous work confirmed that Brd2+/- mouse presents the sex specific characteristics of juvenile myoclonic epilepsy, a subsyndrome of idiopathic generalized epilepsy. Here, we investigated the role of Brd2 gene in modulating the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in the front cortex striata of male mice. Agilent two-color gene expression arrays and the genomic fabric paradigm were used to determine whether the expression and networking of genes involved in the synaptic transmission differ between Brd2+/- and wildtype mice. We found relatively few regulated genes in Brd2+/-mice with respect to their wildtype counterparts. However, most of the regulated genes were directly related to control of anxiety and seizures, justifying the role of Brd2 upstream control of these traits.
Project description:Our previous work showed that Brd2+/- mouse models the sex specific characteristics of juvenile myoclonic epilepsy, a subsyndrome of idiopathic generalized epilepsy. Here, we investigated a role of Brd2 gene in modulating the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in the striatum of female mice. Agilent two-color gene expression arrays and the genomic fabric paradigm were used to determine whether the expression and networking of genes involved in the synaptic transmission differ between Brd2+/- and wildtype mice and whether these differences are sex-specific. As in Brd+/- male mice we found relatively few regulated genes in Brd2+/-female mice with respect to their wildtype counterparts. However, most of the regulated genes were directly related to control of anxiety and seizures, justifying the role of Brd2 upstream control of these traits. Remarkably, the sets of regulated genes in the two sexes did not overlap, supporting the conclusion of sex-specific control of traits by Brd2.
Project description:Calcium channel B subunits (CavB) are mainly recognized for their contribution as regulatory subunits in modulating biophysical and trafficking channel properties. Here, we report for a novel function of the neuronal auxiliary CavB4 subunit in nuclear localization and transcriptional activity. In CA1 hippocampal neurons, nuclear translocation of CavB4 is differentiation-dependent. Similarly, in NG108-15 cell line, the nuclear localization of CavB4 is triggered by cAMP, a neuronal differentiating factor. The nuclear translocation of CavB4 requires an intact SH3 / GK interaction and is lost for a 38 amino acid C-terminal truncated form of the subunit implicated in human juvenile myoclonic epilepsy (CavB4-R482X mutant). The nuclear localization of CavB4 induces the regulation of numerous of genes which is not the case for the human mutation. These data indicate that gene regulation by a calcium channel subunit may contribute to the acquisition of a neuronal phenotype, a process that is disturbed if the nuclear localization is hampered by a mutation implicated in a severe neurological phenotype.
Project description:Extracellular vesicles have been the center of many studies focusing on neuron-to-neuron communication while the role of EVs in progenitor-to-neuron and -astrocyte communication occurring during brain development has not been systematically investigated. In this project, we focus on the physiological characterization, dynamic and function of human EVs during human brain development using human-derived cerebral organoids, neural progenitors, neurons and astrocytes. We examined the composition and function of EVs, in patients with myoclonic epilepsy and find alterations in size, composition and function. This study sheds new light on the biology of EVs during brain development.
Project description:Our previous work confirmed that Brd2+/- mouse presents the sex specific characteristics of juvenile myoclonic epilepsy, a subsyndrome of idiopathic generalized epilepsy. Here, we investigated the role of Brd2 gene in modulating the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in the front cortex striata of male mice. Agilent two-color gene expression arrays and the genomic fabric paradigm were used to determine whether the expression and networking of genes involved in the synaptic transmission differ between Brd2+/- and wildtype mice. We found relatively few regulated genes in Brd2+/-mice with respect to their wildtype counterparts. However, most of the regulated genes were directly related to control of anxiety and seizures, justifying the role of Brd2 upstream control of these traits. Agilent mouse two-color gene expression arrays to profile striata of the prefrontal cortices of wildtype (W) and Brd2+/- (H) mouse male (M) adult C57Bl/6j mice. Differently labeled biological replicates were cohybridized with each array. Results of similarly labeled different conditions were compared then averaged for the two fluorescent labels. For instance: MW1 & MW3 were compared with MH1 & MH3, MW2 & MW4 were compared with MH2 & + MH4, and the results of the comparisons averaged. This design uses 100% of the resources, has a better normlaiztion and allows all possible comparisons among the conditions.
Project description:Our previous work showed that Brd2+/- mouse models the sex specific characteristics of juvenile myoclonic epilepsy, a subsyndrome of idiopathic generalized epilepsy. Here, we investigated a role of Brd2 gene in modulating the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in the striatum of female mice. Agilent two-color gene expression arrays and the genomic fabric paradigm were used to determine whether the expression and networking of genes involved in the synaptic transmission differ between Brd2+/- and wildtype mice and whether these differences are sex-specific. As in Brd+/- male mice we found relatively few regulated genes in Brd2+/-female mice with respect to their wildtype counterparts. However, most of the regulated genes were directly related to control of anxiety and seizures, justifying the role of Brd2 upstream control of these traits. Remarkably, the sets of regulated genes in the two sexes did not overlap, supporting the conclusion of sex-specific control of traits by Brd2. Agilent mouse two-color gene expression arrays to profile striata of the prefrontal cortices of wildtype (W) and Brd2+/- (H) mouse female (F) adult C57Bl/6j mice. Differently labeled biological replicates were cohybridized with each array. Results of similarly labeled different conditions were compared then averaged for the two fluorescent labels. For instance: FW1 & FW3 were compared with FH1 & FH3, FW2 & FW4 were compared with FH2 & + FH4, and the results of the comparisons averaged. This design uses 100% of the resources, has a better normlaiztion and allows all possible comparisons among the conditions.