Elevated reactive aggression in forebrain-specific knockout mice.

Cellular communication network factor 2 (CCN2) is a matricellular protein that plays important roles in connective tissue. CCN2 is also expressed in the nervous system; however, its role is still unclear. To explore CCN2 function in the brain, we generated forebrain-specific knockout (Fb KO) mice.

Dendritic Morphology of Developing Hippocampal Neurons in Cyp11a1 Null Mice.

Introduction: Neurosteroids have a variety of neurological functions, such as neurite growth, neuroprotection, myelination, and neurogenesis. P450scc, encoded by CYP11A1 gene, is the cholesterol side chain cleavage enzyme that catalyzes the first and rate-limiting step in steroidogenesis. In this study, we examine the dendritic morphology in developing hippocampal neurons of Cyp11a1 null mice at P15, a critical period for synapse formation and maturation.

Mature neurons from iPSCs unveil neurodegeneration-related pathways in mucopolysaccharidosis type II: GSK-3β inhibition for therapeutic potential.

Mucopolysaccharidosis (MPS) type II is caused by a deficiency of iduronate-2-sulfatase and is characterized by the accumulation of glycosaminoglycans (GAGs). Without effective therapy, the severe form of MPS II causes progressive neurodegeneration and death. This study generated multiple clones of induced pluripotent stem cells (iPSCs) and their isogenic controls (ISO) from four patients with MPS II neurodegeneration.

Sleep Deprivation Induces Dopamine System Maladaptation and Escalated Corticotrophin-Releasing Factor Signaling in Adolescent Mice.

Sleep disruption is highly associated with the pathogenesis and progression of a wild range of psychiatric disorders. Furthermore, appreciable evidence shows that experimental sleep deprivation (SD) on humans and rodents evokes anomalies in the dopaminergic (DA) signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Since adolescence is a vital period for the maturation of the DA system as well as the occurrence of mental disorders, the present studies aimed to investigate the impacts of SD on the DA system of adolescent mice.

Altered synaptic protein expression, aberrant spine morphology, and impaired spatial memory in Dlgap2 mutant mice, a genetic model of autism spectrum disorder.

A microdeletion of approximately 2.4 Mb at the 8p23 terminal region has been identified in a Taiwanese autistic boy. Among the products transcribed/translated from genes mapped in this region, the reduction of DLGAP2, a postsynaptic scaffold protein, might be involved in the pathogenesis of autism spectrum disorder (ASD).

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control.

Mood disorders are an important public health issue and recent advances in genomic studies have indicated that molecules involved in neurodevelopment are causally related to mood disorders. BLM-s (BCL-2-like molecule, small transcript isoform), a BH3-only proapoptotic BCL-2 family member, mediates apoptosis of postmitotic immature neurons during embryonic cortical development, but its role in the adult brain is unknown. To better understand the physiological role of Blm-s gene in vivo, we generated a Blm-s-knockout (Blm-s) mouse.

Chronic N-Acetylcysteine Treatment Prevents Amphetamine-Induced Hyperactivity in Heterozygous Mutant Mice, a Putative Prodromal Schizophrenia Animal Model.

Symptoms of schizophrenia (SZ) typically emerge during adolescence to young adulthood, which gives a window before full-blown psychosis for early intervention. Strategies for preventing the conversion from the prodromal phase to the psychotic phase are warranted. Heterozygous (Het) mutant mice are considered a prodromal model of SZ, suitable for studying psychotic conversion.

Impaired response to sleep deprivation in heterozygous mutant mice.

Objectives: Sleep/circadian rhythm disturbances are environmental stress factors that might interact with genetic risk factors and contribute to the pathogenesis of psychiatric disorders.

Methods: In this study, the multiple-platform method was used to induce sleep deprivation (SD). We evaluated the impact of 72-hour SD in behavioural, anatomical, and biochemical aspects in heterozygous mutant ( Het) mice, an animal model of schizophrenia.

Altered White Matter and Layer VIb Neurons in Heterozygous Mutant, a Mouse Model of Schizophrenia.

Increased white matter neuron density has been associated with neuropsychiatric disorders including schizophrenia. However, the pathogenic features of these neurons are still largely unknown. Subplate neurons, the earliest generated neurons in the developing cortex have also been associated with schizophrenia and autism.

Voluntary exercise ameliorates synaptic pruning deficits in sleep-deprived adolescent mice.

Adolescence is a critical period for brain development and adequate sleep during this period is essential for physical function and mental health. Emerging evidence has detailed the neurological impacts of sleep insufficiency on adolescents, as was unveiled by our previous study, microglia, one of the crucial contributors to synaptic pruning, is functionally disrupted by lack of sleep. Here, we provided evidence featuring the protective effect and the underlying mechanisms of voluntary exercise (VE) on microglial functions in an adolescent 72 h sleep deprivation (SD) model.

Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a "Two-Hit" Non-Genetic Mouse Model of Schizophrenia.

Schizophrenia is a multifactorial developmental neuropsychiatric disorder. This study examined the interplay of maternal infection and postweaning social isolation, which are prenatal and postnatal risk factors, respectively. Pregnant mice received poly I:C or saline injection on gestation day 9 and the pups were weaned at postnatal day 28.

Mice Lacking Connective Tissue Growth Factor in the Forebrain Exhibit Delayed Seizure Response, Reduced C-Fos Expression and Different Microglial Phenotype Following Acute PTZ Injection.

Connective tissue growth factor (CTGF) plays important roles in the development and regeneration of the connective tissue, yet its function in the nervous system is still not clear. CTGF is expressed in some distinct regions of the brain, including the dorsal endopiriform nucleus (DEPN) which has been recognized as an epileptogenic zone. We generated a forebrain-specific knockout (Fb KO) mouse line in which the expression of Ctgf in the DEPN is eliminated.

An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling.

PHRF1 is involved in transforming growth factor β (TGF-β) signaling to constrain the formation of acute promyelocytic leukemia (APL) in mouse APL models. PHRF1 also participates in modulating non-homologous end-joining. However, the role of PHRF1 in mammalian dendrite architecture and synaptic plasticity is unclear.

Deprivation of Muscleblind-Like Proteins Causes Deficits in Cortical Neuron Distribution and Morphological Changes in Dendritic Spines and Postsynaptic Densities.

Myotonic dystrophy (Dystrophia Myotonica; DM) is the most common adult-onset muscular dystrophy and its brain symptoms seriously affect patients' quality of life. It is caused by extended (CTG) expansions at 3'-UTR of gene (DM type 1, DM1) or (CCTG) repeats in the intron 1 of gene (DM type 2, DM2) and the sequestration of Muscleblind-like (MBNL) family proteins by transcribed (CUG) RNA hairpin is the main pathogenic mechanism for DM. The MBNL proteins are splicing factors regulating posttranscriptional RNA during development.

Microglia-mediated synaptic pruning is impaired in sleep-deprived adolescent mice.

The detrimental effects of sleep insufficiency have been extensively explored. However, only a few studies have addressed this issue in adolescents. In the present study, we examined and compared the effects of 72 h paradoxical sleep deprivation (SD) on adolescent (5 weeks old) and adult (~12 weeks old) mice.

Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter.

Connective tissue growth factor (CTGF) is a secreted extracellular matrix-associated protein, which play a role in regulating various cellular functions. Although the expression of CTGF has been reported in the cortical subplate, its function is still not clear. Thus, to explore the significance of CTGF in the brain, we created a forebrain-specific knockout (Fb KO) mouse model.

Biomaterial aided differentiation and maturation of induced pluripotent stem cells.

Engineering/reprogramming differentiated adult somatic cells to gain the ability to differentiate into any type of cell lineage are called as induced pluripotent stem cells (iPSCs). Offering unlimited self-renewal and differentiation potential, these iPSC are aspired to meet the growing demands in the field of regenerative medicine, tissue engineering, disease modeling, nanotechnology, and drug discovery. Biomaterial fabrication with the rapid evolution of technology increased their versatility and utility in regenerative medicine and tissue engineering, revolutionizing the stem cell biology research with the property to guide the process of proliferation, differentiation, and morphogenesis.

Structural and functional differences in the barrel cortex of Mecp2 null mice.

Functional deficits in sensory systems are commonly noted in neurodevelopmental disorders, such as the Rett syndrome (RTT). Defects in methyl CpG binding protein gene (MECP2) largely accounts for RTT. Manipulations of the Mecp2 gene in mice provide useful models to probe into various aspects of brain development associated with the RTT.

Important roles of Vilse in dendritic architecture and synaptic plasticity.

Vilse/Arhgap39 is a Rho GTPase activating protein (RhoGAP) and utilizes its WW domain to regulate Rac/Cdc42-dependent morphogenesis in Drosophila and murine hippocampal neurons. However, the function of Vilse in mammalian dendrite architecture and synaptic plasticity remained unclear. In the present study, we aimed to explore the possible role of Vilse in dendritic structure and synaptic function in the brain.

Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via β-catenin.

Breast carcinoma amplified sequence 2 (BCAS2) is a core component of the hPrP19 complex that controls RNA splicing. Here, we performed an exon array assay and showed that β-catenin is a target of BCAS2 splicing regulation. The regulation of dendrite growth and morphology by β-catenin is well documented.

RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function.

RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors.

A high-density microelectrode-tissue-microelectrode sandwich platform for application of retinal circuit study.

Background: Microelectrode array (MEA) devices are frequently used in neural circuit studies, especially in retinal prosthesis. For a high throughput stimulation and recording paradigm, it is desirable to obtain the responses of multiple surface RGCs initiated from the electrical signals delivered to multiple photoreceptor cells. This can be achieved by an high density MEA-tissue-MEA (MTM) sandwich configuration.

Functional and structural deficits of the dentate gyrus network coincide with emerging spontaneous seizures in an Scn1a mutant Dravet Syndrome model during development.

Dravet syndrome (DS) is characterized by severe infant-onset myoclonic epilepsy along with delayed psychomotor development and heightened premature mortality. A primary monogenic cause is mutation of the SCN1A gene, which encodes the voltage-gated sodium channel subunit Nav1.1.