TAAR1 agonist ulotaront modulates striatal and hippocampal glutamate function in a state-dependent manner.

Aberrant dopaminergic and glutamatergic function, particularly within the striatum and hippocampus, has repeatedly been associated with the pathophysiology of schizophrenia. Supported by preclinical and recent clinical data, trace amine-associated receptor 1 (TAAR1) agonism has emerged as a potential new treatment approach for schizophrenia. While current evidence implicates TAAR1-mediated regulation of dopaminergic tone as the primary circuit mechanism, little is known about the effects of TAAR1 agonists on the glutamatergic system and excitation-inhibition balance.

Cell-type specific defects in PTEN-mutant cortical organoids converge on abnormal circuit activity.

De novo heterozygous loss-of-function mutations in phosphatase and tensin homolog (PTEN) are strongly associated with autism spectrum disorders; however, it is unclear how heterozygous mutations in this gene affect different cell types during human brain development and how these effects vary across individuals. Here, we used human cortical organoids from different donors to identify cell-type specific developmental events that are affected by heterozygous mutations in PTEN. We profiled individual organoids by single-cell RNA-seq, proteomics and spatial transcriptomics and revealed abnormalities in developmental timing in human outer radial glia progenitors and deep-layer cortical projection neurons, which varied with the donor genetic background.

An analysis of shapes and location of anterior hairline in Asian men.

An individual's first impression can be influenced by a number of esthetic factors, one of which is a natural hairline. The anterior hairline can be affected by various factors, such as race, age, forehead shape, and hair loss progression, similar to androgenetic alopecia. Information on the shape, hairline location on the forehead, and race are required to classify the anterior hairline.

Autism genes converge on asynchronous development of shared neuron classes.

Genetic risk for autism spectrum disorder (ASD) is associated with hundreds of genes spanning a wide range of biological functions. The alterations in the human brain resulting from mutations in these genes remain unclear. Furthermore, their phenotypic manifestation varies across individuals.

Molecular logic of cellular diversification in the mouse cerebral cortex.

The mammalian cerebral cortex has an unparalleled diversity of cell types, which are generated during development through a series of temporally orchestrated events that are under tight evolutionary constraint and are critical for proper cortical assembly and function. However, the molecular logic that governs the establishment and organization of cortical cell types remains unknown, largely due to the large number of cell classes that undergo dynamic cell-state transitions over extended developmental timelines. Here we generate a comprehensive atlas of the developing mouse neocortex, using single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin using sequencing.

Neuron class-specific responses govern adaptive myelin remodeling in the neocortex.

Myelin plasticity is critical for neurological function, including learning and memory. However, it is unknown whether this plasticity reflects uniform changes across all neuronal subtypes, or whether myelin dynamics vary between neuronal classes to enable fine-tuning of adaptive circuit responses. We performed in vivo two-photon imaging of myelin sheaths along single axons of excitatory callosal neurons and inhibitory parvalbumin-expressing interneurons in adult mouse visual cortex.

Effects of Sedation Performed by an Anesthesiologist on Pediatric Endoscopy: a Single-Center Retrospective Study in Korea.

Background: Endoscopy is used for diagnosing and treating various digestive diseases in children as well as in adults. However, in pediatric patients, it is recommended that sufficient sedation should be ensured before conducting endoscopy, since insufficient sedation may cause serious complications. However, in Korea, no studies have yet described the types of sedation drugs, effects of sedation, and efficiency of endoscopy with respect to the sedation instructor.

Differential Coupling of Adult-Born Granule Cells to Parvalbumin and Somatostatin Interneurons.

A strong GABAergic tone imposes sparse levels of activity in the dentate gyrus of the hippocampus. This balance is challenged by the addition of new granule cells (GCs) with high excitability. How developing GCs integrate within local inhibitory networks remains unknown.

Breast Cancer Estimate Modeling via PDE Thermal Analysis Algorithms.

The significance of this study lies in the importance of (1) nondestructive testing in defect studies and (2) securing the reliability of breast cancer prediction through thermal analysis in nondestructive testing. Most nondestructive tests have negative effects on the human body. Moreover, the precision and accuracy of such tests are poor.

Effects of Several Cosmetic Preservatives on ROS-Dependent Apoptosis of Rat Neural Progenitor Cells.

Benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea are commonly used preservatives in cosmetics. Recent reports suggested that these compounds may have cellular and systemic toxicity in high concentration. In addition, diazolidinyl urea and imidazolidinyl urea are known formaldehyde (FA) releasers, raising concerns for these cosmetic preservatives.

LBEC0101, A Proposed Etanercept Biosimilar: Pharmacokinetics, Immunogenicity, and Tolerability Profiles Compared with a Reference Biologic Product in Healthy Male Subjects.

Objectives: We performed this study to compare the pharmacokinetic (PK), immunogenicity, and tolerability profiles of etanercept between LBEC0101, a proposed biosimilar, and Enbrel, the reference biological product.

Methods: A randomized, double-blind, single-dose, two-treatment, two-period, two-sequence, crossover study was conducted in 48 healthy males. In each period, a single dose of LBEC0101 or Enbrel was subcutaneously injected at 25 mg and serial blood samples for PK evaluation were collected up to 648 h post-dose.

The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy.

Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD.

Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism.

Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry.

A disynaptic feedback network activated by experience promotes the integration of new granule cells.

Experience shapes the development and connectivity of adult-born granule cells (GCs) through mechanisms that are poorly understood. We examined the remodeling of dentate gyrus microcircuits in mice in an enriched environment (EE). Short exposure to EE during early development of new GCs accelerated their functional integration.

Effects of Triclosan on Neural Stem Cell Viability and Survival.

Triclosan is an antimicrobial or sanitizing agent used in personal care and household products such as toothpaste, soaps, mouthwashes and kitchen utensils. There are increasing evidence of the potentially harmful effects of triclosan in many systemic and cellular processes of the body. In this study, we investigated the effects of triclosan in the survivability of cultured rat neural stem cells (NSCs).

Reliable Genetic Labeling of Adult-Born Dentate Granule Cells Using Ascl1 CreERT2 and Glast CreERT2 Murine Lines.

Unlabelled: Newly generated dentate granule cells (GCs) are relevant for input discrimination in the adult hippocampus. Yet, their precise contribution to information processing remains unclear. To address this question, it is essential to develop approaches to precisely label entire cohorts of adult-born GCs.

High sucrose consumption during pregnancy induced ADHD-like behavioral phenotypes in mice offspring.

In recent years, the average consumption of sugar in humans from all ages has remarkably increased, exceeding the recommended limit. Pregnancy is a critical time for the global development of offsprings who are vulnerable to the deleterious effects of environmental factors. In this study, we investigated whether high sucrose consumption during pregnancy could affect the attention-deficit hyperactivity disorder (ADHD)-like neurobehavioral outcomes in offspring mice.

The Epigenetic Reader BRD2 as a Specific Modulator of PAI-1 Expression in Lipopolysaccharide-Stimulated Mouse Primary Astrocytes.

The post translational modification of lysine acetylation is a key mechanism that regulates chromatin structure. Epigenetic readers, such as the BET domains, are responsible for reading histone lysine acetylation which is a hallmark of open chromatin structure, further providing a scaffold that can be accessed by RNA polymerases as well as transcription factors. Recently, several reports have assessed and highlighted the roles of epigenetic readers in various cellular contexts.

Dynamic role of adult-born dentate granule cells in memory processing.

Throughout the adult life of all mammals including humans, new neurons are incorporated to the dentate gyrus of the hippocampus. During a critical window that lasts about two weeks, adult-born immature neurons are more excitable and plastic than mature ones, and they respond to a wider range of inputs. In apparent contradiction, new neurons have been shown to be crucial to solve behavioral tasks that involve the discrimination of very similar situations, which would instead require high input specificity.

Repeated neonatal propofol administration induces sex-dependent long-term impairments on spatial and recognition memory in rats.

Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment.

A critical period for experience-dependent remodeling of adult-born neuron connectivity.

Neurogenesis in the dentate gyrus (DG) of the adult hippocampus is a process regulated by experience. To understand whether experience also modifies the connectivity of new neurons, we systematically investigated changes in their innervation following environmental enrichment (EE). We found that EE exposure between 2-6 weeks following neuron birth, rather than merely increasing the number of new neurons, profoundly affected their pattern of monosynaptic inputs.