The expansion of newborn neurons in hippocampus improves social recognition deficit in a mouse model of autism.

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by core symptoms of impaired social interaction and communication. The pathological mechanism and treatment are not clear and need further study. Our previous study found that the deletion of high-risk gene Autism Susceptibility 2 (AUTS2) in mice led to dentate gyrus (DG) hypoplasia that highly associated with impaired social novelty recognition.

deletion involves in DG hypoplasia and social recognition deficit: The developmental and neural circuit mechanisms.

The involvement of genetic risk and the underlying developmental and neural circuit mechanisms in autism-related social deficit are largely unclear. Here, we report that deletion of , a high-susceptibility gene of ASDs, caused postnatal dentate gyrus (DG) hypoplasia, which was closely relevant to social recognition deficit. Furthermore, a previously unknown mechanism for neural cell migration in postnatal DG development was identified, in which Auts2-related signaling played a vital role as the transcription repressor.

RhoGEF Trio Regulates Radial Migration of Projection Neurons via Its Distinct Domains.

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID.

Dysfunction of Trio GEF1 involves in excitatory/inhibitory imbalance and autism-like behaviors through regulation of interneuron migration.

Autism spectrum disorders (ASDs) are a group of highly inheritable neurodevelopmental disorders. Functional mutations in TRIO, especially in the GEF1 domain, are strongly implicated in ASDs, whereas the underlying neurobiological pathogenesis and molecular mechanisms remain to be clarified. Here we characterize the abnormal morphology and behavior of embryonic migratory interneurons (INs) upon Trio deficiency or GEF1 mutation in mice, which are mediated by the Trio GEF1-Rac1 activation and involved in SDF1α/CXCR4 signaling.

The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling.

Previous genetic and biological evidence converge on the involvement of synaptic dysfunction in schizophrenia, and OPCML, encoding a synaptic membrane protein, is reported to be genetically associated with schizophrenia. However, its role in the pathophysiology of schizophrenia remains largely unknown. Here, we found that Opcml is strongly expressed in the mouse hippocampus; ablation of Opcml leads to reduced phosphorylated cofilin and dysregulated F-actin dynamics, which disturbs the spine maturation.

Plasma total antioxidant status and cognitive impairments in first-episode drug-naïve patients with schizophrenia.

Accumulating evidence suggest that excessive reactive oxygen species-induced oxidative damage may underlie neurodegeneration and cognitive impairment in several disorders including schizophrenia. In this study we examined the association of oxidative stress with cognitive deficits in first-episode drug-naïve (FEDN) patients with schizophrenia. We recruited 54 FEDN patients and 50 age- and sex-matched healthy controls and examined the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus cognitive Battery (MCCB) and plasma total antioxidant status (TAS).

P-Rex1 Overexpression Results in Aberrant Neuronal Polarity and Psychosis-Related Behaviors.

Neuronal polarity is involved in multiple developmental stages, including cortical neuron migration, multipolar-to-bipolar transition, axon initiation, apical/basal dendrite differentiation, and spine formation. All of these processes are associated with the cytoskeleton and are regulated by precise timing and by controlling gene expression. The P-Rex1 (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1) gene for example, is known to be important for cytoskeletal reorganization, cell motility, and migration.