Girdin deficiency causes developmental and epileptic encephalopathy with hippocampal sclerosis and interneuronopathy.

Objective: Loss-of-function mutations in the GIRDIN/CCDC88A gene cause developmental epileptic encephalopathy (DEE) in humans. However, its pathogenesis is largely unknown. Global knockout mice of the corresponding orthologous gene (gKOs) have a preweaning lethal phenotype with growth failure, preventing longitudinal analysis.

GABAergic circuit interaction between central amygdala and bed nucleus of the stria terminalis in lipopolysaccharide-induced despair-like behavior.

Hyperexcitability of central amygdala (CeA) induces depressive symptoms. The bed nucleus of the stria terminalis (BNST) receives GABAergic input from the CeA. However, it remains unclear whether the GABAergic neurons in the CeA projecting to BNST contribute to major depression.

Expression analysis of type I ARF small GTPases ARF1-3 during mouse brain development.

Background: ARF (ADP-ribosylation factor) GTPases are major regulators of intracellular trafficking, and classified into 3 groups (Type I - III), among which the type I group members, ARF1 and 3, are responsible genes for neurodevelopmental disorders.

Methods: In this study, we analysed the expression of Type I ARFs ARF1-3 during mouse brain development using biochemical and morphological methods.

Results: Western blotting analyses revealed that ARF1-3 are weakly expressed in the mouse brain at embryonic day 13 and gradually increase until postnatal day 30.

Expression Analyses of C-Terminal-Binding Protein 1 (CtBP1) during Mouse Brain Development.

Introduction: C-terminal-binding protein 1 (CtBP1) is a multi-functional protein with well-established roles as a transcriptional co-repressor in the nucleus and a regulator of membrane fission in the cytoplasm. Although CtBP1 gene abnormalities have been reported to cause neurodevelopmental disorders, the physiological role and expression profile of CtBP1 remains to be elucidated.

Methods: In this study, we used biochemical, immunohistochemical, and immunofluorescence methods to analyze the expression of CtBP1 during mouse brain development.

Expression analyses of WAC, a responsible gene for neurodevelopmental disorders, during mouse brain development.

WAC is an adaptor protein involved in gene transcription, protein ubiquitination, and autophagy. Accumulating evidence indicates that WAC gene abnormalities are responsible for neurodevelopmental disorders. In this study, we prepared anti-WAC antibody, and performed biochemical and morphological characterization focusing on mouse brain development.

Histological Analysis of a Mouse Model of the 22q11.2 Microdeletion Syndrome.

22q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of developing various psychiatric and developmental disorders, including schizophrenia and early-onset Parkinson's disease.

High Salt Intake Induces Active Coping Behaviors by Enhancing the Resilience against Psychological Stress in Mice.

Background: High salt intake increases the active coping behavior during psychological stress. Acute fear-related severe stress enhances passive coping behavior during subsequent inescapable stress.

Methods: We investigated the effect of high salt intake (2%) for 5 consecutive days on the coping behavior in C57BL6 mice which employing the tail suspension test (TST) at 1 h after the exposure to inescapable innate fear using 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a synthetic component of fox feces.

BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation.

Background: Malignant mesothelioma (MM) is an aggressive mesothelial cell cancer type linked mainly to asbestos inhalation. MM characterizes by rapid progression and resistance to standard therapeutic modalities such as surgery, chemotherapy, and radiotherapy. Our previous studies have suggested that tumor cell-derived connective tissue growth factor (CTGF) regulates the proliferation of MM cells as well as the tumor growth in mouse xenograft models.

Formation of False Context Fear Memory Is Regulated by Hypothalamic Corticotropin-Releasing Factor in Mice.

Traumatic events frequently produce false fear memories. We investigated the effect of hypothalamic corticotropin-releasing factor (CRF) knockdown (Hy--KD) or overexpression (Hy-CRF-OE) on contextual fear memory, as fear stress-released CRF and hypothalamic-pituitary-adrenal axis activation affects the memory system. Mice were placed in a chamber with an electric footshock as a conditioning stimulus (CS) in Context A, then exposed to a novel chamber without CS, as Context B, at 3 h (B-3h) or 24 h (B-24h).

The α1-adrenergic receptors in the amygdala regulate the induction of learned despair through protein kinase C-beta signaling.

Hyperactivity of amygdala is observed in patients with major depressive disorder. Although the role of α1-adrenoceptor in amygdala on fear memory has been well studied, the role of α1-adrenoceptor in amygdala on depression-like behaviors remains unclear. Therefore, we investigated the effect of α1A-adrenoreceptor in amygdala on despair behavior, evaluated by the immobility time during tail suspension test (TST), pharmacological intervention, and immunohistological methods.

Acute inactivation of the serine-threonine kinase Stk25 disrupts neuronal migration.

Background: Neuronal migration involves the directional migration of immature neurons. During much of the migration period these neurons are polarized with defined leading and trailing processes. Stk25 has been shown to bind to the LKB1 activator STRAD and regulate neuronal polarization and dendritogenesis in an opposing manner to Reelin-Dab1 signaling.

Identification of Stk25 as a genetic modifier of Tau phosphorylation in Dab1-mutant mice.

Hyperphosphorylation of the microtubule binding protein Tau is a feature of a number of neurodegenerative diseases, including Alzheimer's disease. Tau is hyperphosphorylated in the hippocampus of dab1-null mice in a strain-dependent manner; however, it has not been clear if the Tau phosphorylation phenotype is a secondary effect of the morbidity of these mutants. The dab1 gene encodes a docking protein that is required for normal brain lamination and dendritogenesis as part of the Reelin signaling pathway.

Reelin and stk25 have opposing roles in neuronal polarization and dendritic Golgi deployment.

The Reelin ligand regulates a Dab1-dependent signaling pathway required for brain lamination and normal dendritogenesis, but the specific mechanisms underlying these actions remain unclear. We find that Stk25, a modifier of Reelin-Dab1 signaling, regulates Golgi morphology and neuronal polarization as part of an LKB1-Stk25-Golgi matrix protein 130 (GM130) signaling pathway. Overexpression of Stk25 induces Golgi condensation and multiple axons, both of which are rescued by Reelin treatment.

Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis.

The reelin signaling pathway regulates nervous system function after birth, in addition to its role in regulating neuronal positioning during embryogenesis. The receptor-dependent, reelin-induced tyrosine phosphorylation of the Dab1 docking protein is an established prerequisite for biological responses to this ligand. Here we show that the inactivation of a conditional Dab1 allele reduces process complexity in correctly positioned neurons in the CA1 region of the mouse hippocampus after birth.

Gene expression profiling during the embryonic development of mouse brain using an oligonucleotide-based microarray system.

We analyzed gene expression profiles in embryonic day 12, 15, 18 and postnatal day 0 mouse brains by utilizing a GeneChip microarray. Significant differential expression was observed in 1413 of 12,422 (11.4%) represented on the chip.