Plasma D-asparagine and the D/L-serine ratio reflect chronic kidney diseases in children regardless of physique.

Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development.

A Pathogenic Missense Mutation in Kainate Receptors Elevates Dendritic Excitability and Synaptic Integration through Dysregulation of SK Channels.

Numerous rare variants that cause neurodevelopmental disorders (NDDs) occur within genes encoding synaptic proteins, including ionotropic glutamate receptors. However, in many cases, it remains unclear how damaging missense variants affect brain function. We determined the physiological consequences of an NDD causing missense mutation in the kainate receptor (KAR) gene, that results in a single amino acid change p.

The Antiseizure Drug Perampanel Is a Subunit-Selective Negative Allosteric Modulator of Kainate Receptors.

Perampanel (PMP) is a third-generation antiseizure drug reported to be a potent and selective noncompetitive negative allosteric modulator of one subfamily of ionotropic glutamate receptor (iGluR), the α-amino-3-hydroxy-S-methylisoxazole-4-propionic acid receptors (AMPARs). However, the recent structural resolution of AMPARs in complex with PMP revealed that its binding pocket is formed from residues that are largely conserved in two members of another family of iGluRs, the GluK4 and GluK5 kainate receptor (KAR) subunits. We show here that PMP inhibits both recombinant and neuronal KARs, contrary to the previous reports, and that the negative allosteric modulator (NAM) activity requires GluK5 subunits to be channel constituents.

Low-Intensity Exercise Suppresses CCAAT/Enhancer-Binding Protein δ/Myostatin Pathway Through Androgen Receptor in Muscle Cells.

Background: Androgen production following exercise has been suggested to contribute anabolic actions of muscle. However, the underlying mechanisms of the androgen receptor (AR) in androgen's action are still unclear.

Objective: In the present study, we examined androgen/AR-mediated action in exercise, especially for the suppression of myostatin, a potent negative regulator of muscle mass.

Establishment of Novel Murine Model showing Vascular Inflammation-derived Cognitive Dysfunction.

Inflammation is a critical feature of aging and its related diseases, including cardiovascular diseases. Recent epidemiological studies demonstrated that abdominal aortic aneurysm (AAA), an aging-related vascular pathological condition, is associated with cognitive decline. However, the underlying mechanism, especially the role of vascular inflammation, is largely unknown because of lack of an available animal model.

Environmental and physical factors predisposing middle-aged and older Japanese adults to falls and fall-related fractures in the home.

Aim: To identify environmental and physical factors that predispose middle-aged and older Japanese adults to falls and fall-related fractures in the home.

Methods: A cross-sectional survey was carried out in 2014. Self-administered questionnaires were distributed to 15 000 community-dwelling adults in Japan.

Age-dependency of the serum oxidative level in the senescence-accelerated mouse prone 8.

Systemic oxidative stress is considered to cause aging. In this study, to estimate the oxidative stress level in senescence-accelerated mouse prone 8 (SAMP8), we evaluated serum reactive oxygen species production and reduction capacity by measurement of Diacron-Reactive Oxygen Metabolites (d-ROM) and Biological Antioxidant Potential (BAP), respectively, with age. SAMP8 showed earlier increase of d-ROM value with age than SAM resistant 1 (SAMR1), the control strain.

Early attenuation of long-term potentiation in senescence-accelerated mouse prone 8.

Senescence-accelerated mouse (SAM) is an experimental model animal showing a short lifespan and rapid advancement of senescence. Especially, SAM prone 8 (SAMP8) shows age-related impairment of learning and memory, and thus, it is a good model for age-related cognitive function. However, the synaptic characteristics related to cognitive function of SAMP8 have been poorly understood.

Chronic administration of N-acetyl-D-mannosamine improves age-associated impairment of long-term potentiation in the senescence-accelerated mouse.

N-Acetyl-D-mannosamine (ManNAc), a precursor of a sialic acid, is recently reported to improve the cognitive function in aged animals. However, the effect of chronic administration of ManNAc on impaired synaptic transmission and plasticity with age still remain unknown. In this study, we electrophysiologically determined the effect of chronic administration of ManNAc on deteriorated synaptic transmission and plasticity using hippocampal slices from senescence-accelerated mouse prone 8 (SAMP8) which shows age-related impairment of learning and memory.