An enriched environment ameliorates the reduction of parvalbumin-positive interneurons in the medial prefrontal cortex caused by maternal separation early in life.

Early child maltreatment, such as child abuse and neglect, is well known to affect the development of social skills. However, the mechanisms by which such an adverse environment interrupts the development of social skills remain unelucidated. Identifying the period and brain regions that are susceptible to adverse environments can lead to appropriate developmental care later in life.

PLAAT1 deficiency alleviates high-fat diet-induced hepatic lipid accumulation in mice.

The phospholipase A and acyltransferase (PLAAT) family is composed of three isoforms in mice (PLAAT1, 3, and 5), all of which function as phospholipid-metabolizing enzymes exhibiting phospholipase A /A and acyltransferase activities. Plaat3-deficient (Plaat3 ) mice were previously reported to show lean phenotype and remarkable hepatic fat accumulation under high-fat diet (HFD) feeding, while Plaat1 mice have not been analyzed. In the present study, we generated Plaat1 mice and investigated the effects of PLAAT1 deficiency on HFD-induced obesity, hepatic lipid accumulation, and insulin resistance.

Genetic and histopathological analysis of spermatogenesis after short-term testicular torsion in rats.

Background: Patients with testicular torsion (TT) may exhibit impaired spermatogenesis from reperfusion injury after detorsion surgery. Alteration in the expressions of spermatogenesis-related genes induced by TT have not been fully elucidated.

Methods: Eight-week-old Sprague-Dawley rats were grouped as follows: group 1 (sham-operated), group 2 (TT without reperfusion) and group 3 (TT with reperfusion).

Impact of hydrogen gas inhalation during therapeutic hypothermia on cerebral hemodynamics and oxygenation in the asphyxiated piglet.

We previously reported the neuroprotective potential of combined hydrogen (H) gas ventilation therapy and therapeutic hypothermia (TH) by assessing the short-term neurological outcomes and histological findings of 5-day neonatal hypoxic-ischemic (HI) encephalopathy piglets. However, the effects of H gas on cerebral circulation and oxygen metabolism and on prognosis were unknown. Here, we used near-infrared time-resolved spectroscopy to compare combined H gas ventilation and TH with TH alone.

Formation of N-acyl-phosphatidylethanolamines by cytosolic phospholipase Aε in an ex vivo murine model of brain ischemia.

N-Acyl-phosphatidylethanolamines (NAPEs), a minor class of membrane glycerophospholipids, accumulate along with their bioactive metabolites, N-acylethanolamines (NAEs) during ischemia. NAPEs can be formed through N-acylation of phosphatidylethanolamine by cytosolic phospholipase Aε (cPLAε, also known as PLA2G4E) or members of the phospholipase A and acyltransferase (PLAAT) family. However, the enzyme responsible for the NAPE production in brain ischemia has not yet been clarified.

Cerebral hemodynamic response during the resuscitation period after hypoxic-ischemic insult predicts brain injury on day 5 after insult in newborn piglets.

Perinatal hypoxic-ischemic brain injury of neonates remains a significant problem worldwide. During the resuscitation period, changes in cerebral hemoglobin oxygen saturation (ScO) have been identified by near-infrared spectroscopy (NIRS). However, in asphyxiated neonates, the relationship between these changes and brain injury is not known.

Ethanol concentration induces production of 3,4-dihydroxyphenylacetic acid and homovanillic acid in mouse brain through activation of monoamine oxidase pathway.

First, we aimed to investigate ex vivo the effects of ethanol (EtOH) on levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and their metabolites in the frontal cortex, hippocampus, and striatum of Aldh2-knockout (Aldh2-KO) and wild-type (WT) mice. Animals were treated intraperitoneally with saline (control) or EtOH (1.0, 2.

Brain-derived neurotrophic factor predominantly regulates the expression of synapse-related genes in the striatum: Insights from in vitro transcriptomics.

Aim: The striatum, a main component of the basal ganglia, is a critical part of the motor and reward systems of the brain. It consists of GABAergic and cholinergic neurons and receives projections of dopaminergic, glutamatergic, and serotonergic neurons from other brain regions. Brain-derived neurotrophic factor (BDNF) plays multiple roles in the central nervous system, and striatal BDNF has been suggested to be involved in psychiatric and neurodegenerative disorders.

Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells.

Epithelial-mesenchymal transition (EMT) in primary tumor cells is a key prerequisite for metastasis initiation. Statins, cholesterol-lowering drugs, can delay metastasis formation in vivo and attenuate the growth and proliferation of tumor cells in vitro. The latter effect is stronger in tumor cells with a mesenchymal-like phenotype than in those with an epithelial one.

Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development.

It is widely accepted that maternal separation (MS) induces stress in children and disrupts neural circuit formation during early brain development. Even though such disruption occurs transiently early in life, its influence persists after maturation, and could lead to various neurodevelopmental disorders. Our recent study revealed that repeated MS reduces the number of inhibitory neurons and synapses in the medial prefrontal cortex (mPFC) and causes mPFC-related social deficits after maturation.

Meganuclease-Based Artificial Transcription Factors.

Embedding middle-scale artificial gene networks in live mammalian cells is one of the most important future goals for cell engineering. However, the applications of the highly orthogonal and conventional artificial transcription factors currently available are limited. In this study, we present a scalable pipeline to produce artificial transcription factors based on homing endonucleases, also known as meganucleases.

Vexin is upregulated in cerebral cortical neurons by brain-derived neurotrophic factor.

Aim: Chromosome 8 open reading frame 46 (C8orf46), a human protein-coding gene, has recently been named Vexin. A recent study indicated that Vexin is involved in embryonic neurogenesis. Additionally, some transcriptomic studies detected changes in the mRNA levels of patients with psychiatric and neurological diseases.

The effects of early life stress on the excitatory/inhibitory balance of the medial prefrontal cortex.

Aversive environmental conditions during early life are known to cause long-lasting social deficits, similar to those observed in patients with neurodevelopmental disorders. However, the mechanism of how early life stress can cause social deficits is not well understood. To clarify how being in an aversive environment during development affects sociability, we conducted various analyses focusing on the excitatory and inhibitory (E/I) balance in the medial prefrontal cortex (mPFC) and how it is related to social deficits, with young adult male rats that had been exposed to maternal separation (MS).

Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model.

Despite its poor outcomes, therapeutic hypothermia (TH) is the current standard treatment for neonatal hypoxic-ischaemic encephalopathy (HIE). In this study, due to its antioxidant, anti-inflammatory, and antiapoptotic properties, the effectiveness of molecular hydrogen (H) combined with TH was evaluated by means of neurological and histological assessments. Piglets were divided into three groups: hypoxic-ischaemic insult with normothermia (NT), insult with hypothermia (TH, 33.

Corticotropin-releasing hormone-binding protein is up-regulated by brain-derived neurotrophic factor and is secreted in an activity-dependent manner in rat cerebral cortical neurons.

A recent study revealed that corticotropin-releasing hormone (CRH) in the cerebral cortex (CTX) plays a regulatory role in emotional behaviors in rodents. Given the functional interaction between brain-derived neurotrophic factor (BDNF) and the CRH-signaling pathway in the hypothalamic-pituitary-adrenal axis, we hypothesized that BDNF may regulate gene expression of CRH and its related molecules in the CTX. Findings of real-time quantitative PCR (RT-qPCR) indicated that stimulation of cultured rat cortical neurons with BDNF led to marked elevations in the mRNA levels of CRH and CRH-binding protein (CRH-BP).

Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development.

Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development.

Functional interaction between BDNF and mGluR II in vitro: BDNF down-regulated mGluR II gene expression and an mGluR II agonist enhanced BDNF-induced BDNF gene expression in rat cerebral cortical neurons.

Accumulating evidence suggests functional interaction between brain-derived neurotrophic factor (BDNF) and metabotropic glutamate receptor (mGluR) signaling pathways in the central nervous system (CNS). To date, eight subtypes of mGluRs, mGluR1-8, have been identified, and a previous study suggested that BDNF leads to down-regulation of GluR2 mRNA in rat cerebral cortical cultures. However, precise transcriptomic effects of BDNF on other mGluRs and their cellular significance on the BDNF signaling pathway remain largely unknown.

A unique pattern of bisphenol a effects on nerve growth factor gene expression in embryonic mouse hypothalamic cell line N-44.

We investigated the toxicity of bisphenol A (BPA) by determining the gene expression of nerve growth factor (Ngf in the embryonic mouse cell line mHypoE-N44 derived from the hypothalamus exposed to BPA dose range between 0.02 and 200 μmol L-1 for 3 h. Ngf mRNA levels decreased in a dose-dependent manner, with significant reductions observed in the 2 to 50 μmol L-1 BPA treatment groups compared to controls.

Development of an artificial calcium-dependent transcription factor to detect sustained intracellular calcium elevation.

The development of a synthetic transcription factor that responds to intracellular calcium signals enables analyzing cellular events at the single-cell level or "rewiring" the intracellular information networks. In this study, we developed the calcium-dependent transcription factor (CaTF), which was cleaved by calpain and then translocated to the nuclei where it induced reporter expression. Our results demonstrated that CaTF-mediated reporter expression was stable and responded to the intracellular calcium level and calpain activity.

Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity.

The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague-Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3h each day during the 10-15 postnatal days.

Prolonged maternal separation disturbs the serotonergic system during early brain development.

Early life stress interrupts brain development through the disturbance of various neurotransmitter and neurotrophic factor activities, but the details remain unclear. In the current study, we focused on the serotonergic system, which plays a critical role in brain development, and examined the time-dependent influence of prolonged maternal separation on male Sprague-Dawley rats. The rats were separated from their dams for 3h twice-daily during postnatal days (PDs) 2-20.