Resistance exercise in early-stage ALS patients, ALSFRS-R, Sickness Impact Profile ALS-19, and muscle transcriptome: a pilot study.

Amyotrophic lateral sclerosis (ALS) patients lack effective treatments to maintain motor and neuromuscular function. This study aimed to evaluate the effect of a home-based exercise program on muscle strength, ALS scores, and transcriptome in ALS patients, Clinical Trials.gov #NCT03201991 (28/06/2017).

Vitamin C transporter SVCT1 serves a physiological role as a urate importer: functional analyses and in vivo investigations.

Uric acid, the end product of purine metabolism in humans, is crucial because of its anti-oxidant activity and a causal relationship with hyperuricemia and gout. Several physiologically important urate transporters regulate this water-soluble metabolite in the human body; however, the existence of latent transporters has been suggested in the literature. We focused on the Escherichia coli urate transporter YgfU, a nucleobase-ascorbate transporter (NAT) family member, to address this issue.

SLC23A3 is a renal hypoxanthine transporter.

LLC-PK1 renal cells show Na-dependent and Na-independent hypoxanthine uptake. While the latter is inhibited by adenine, neither are inhibited by xanthine. In rats, intestinal Na-dependent hypoxanthine transporter Slc23a4 is not expressed in the kidney, and its action is inhibited by xanthine.

Xanthine Oxidoreductase Inhibitors Suppress the Onset of Exercise-Induced AKI in High HPRT Activity - Double Knockout Mice.

Background: Hereditary renal hypouricemia type 1 (RHUC1) is caused by URAT1/SLC22A12 dysfunction, resulting in urolithiasis and exercise-induced AKI (EIAKI). However, because there is no useful experimental RHUC1 animal model, the precise pathophysiologic mechanisms underlying EIAKI have yet to be elucidated. We established a high HPRT activity - double knockout (DKO) mouse as a novel RHUC1 animal model for investigating the cause of EIAKI and the potential therapeutic effect of xanthine oxidoreductase inhibitors (XOIs).

The Lactate Receptor HCA Is Present in the Choroid Plexus, the Tela Choroidea, and the Neuroepithelial Lining of the Dorsal Part of the Third Ventricle.

The volume, composition, and movement of the cerebrospinal fluid (CSF) are important for brain physiology, pathology, and diagnostics. Nevertheless, few studies have focused on the main structure that produces CSF, the choroid plexus (CP). Due to the presence of monocarboxylate transporters (MCTs) in the CP, changes in blood and brain lactate levels are reflected in the CSF.

Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function.

The oxidant/antioxidant imbalance plays a pivotal role in the lung. Uric acid (UA), an endogenous antioxidant, is highly present in lung tissue, however, its impact on lung function under pathophysiological conditions remains unknown. In this work, pharmacological and genetic inhibition of UA metabolism in experimental mouse models of acute and chronic obstructive pulmonary disease (COPD) revealed that increased plasma UA levels improved emphysematous phenotype and lung dysfunction in accordance with reduced oxidative stress specifically in female but not in male mice, despite no impact of plasma UA induction on the pulmonary phenotypes in nondiseased mice.

Xanthine oxidoreductase knockout mice with high HPRT activity were not rescued by NAD replenishment.

Although xanthinuria is nonfatal in human, xanthine oxidoreductase knockout (KO) mice have only a short lifespan. Hypoxanthine phosphoribosyltransferase activity (HPRT) in human and wild mice is higher than in laboratory mice. The aim of this study was to investigate the underlying mechanisms that give rise to the longer lifespan of high-HPRT/KO mice.

Perfecting a high hypoxanthine phosphoribosyltransferase activity-uricase KO mice to test the effects of purine- and non-purine-type xanthine dehydrogenase (XDH) inhibitors.

Background And Purpose: Purine metabolism in mice and human differ in terms of uricase (Uox) activity as well as hypoxanthine phosphoribosyltransferase (HPRT) activity. The aim of this study was the establishment of high HPRT activity-Uox knockout (KO) mice as a novel hyperuricaemic model. Then to investigate the effects of purine-type xanthine dehydrogenase (XDH) inhibitor, allopurinol, and non-purine-type XDH inhibitor, topiroxostat, on purine metabolism.

Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice.

Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory.

Immunohistochemical and in situ hybridization study of urate transporters GLUT9/URATv1, ABCG2, and URAT1 in the murine brain.

Background: Uric acid (UA) is known to exert neuroprotective effects in the brain. However, the mechanism of UA regulation in the brain is not well characterized. In our previous study, we described that the mouse urate transporter URAT1 is localized to the cilia and apical surface of ventricular ependymal cells.

Urat1-Uox double knockout mice are experimental animal models of renal hypouricemia and exercise-induced acute kidney injury.

Renal hypouricemia (RHUC) is a hereditary disease characterized by a low level of plasma urate but with normal urinary urate excretion. RHUC type 1 is caused by mutations of the urate transporter URAT1 gene (SLC22A12). However, the plasma urate levels of URAT1 knockout mice are no different from those of wild-type mice.

The Mechanism of False in Vitro Elevation of Uric Acid Level in Mouse Blood.

Thirty minutes incubation at room temperature elevates the uric acid (UA) level of mouse blood in a test tube, and has previously been reported as "false in vitro elevation of the uric acid level." However the UA level of human blood does not elevate using the same incubation. We clarified the mechanism of the false in vitro UA elevation using mice with highly active hypoxanthine phosphoribosyl transferase (Hprt) of B6-ChrXC(MSM), a consomic mouse strain with the chromosome portion of Mus musculus morocinus in the Hprt gene site, or mice with a targeted deletion of the urate oxidase gene (Uox) (Uox-knockout (KO)).

Elfn1 recruits presynaptic mGluR7 in trans and its loss results in seizures.

GABAergic interneurons are highly heterogeneous, and much is unknown about the specification and functional roles of their neural circuits. Here we show that a transinteraction of Elfn1 and mGluR7 controls targeted interneuron synapse development and that loss of Elfn1 results in hyperactivity and sensory-triggered epileptic seizures in mice. Elfn1 protein increases during postnatal development and localizes to postsynaptic sites of somatostatin-containing interneurons (SOM-INs) in the hippocampal CA1 stratum oriens and dentate gyrus (DG) hilus.

False in vitro and in vivo elevations of uric acid levels in mouse blood.

Uric acid (UA) levels in mouse blood have been reported to range widely from 0.1 μM to 760 μM. The aim of this study was to demonstrate false in vitro and in vivo elevations of UA levels in mouse blood.

Ependymal cells of the mouse brain express urate transporter 1 (URAT1).

Background: Elevated uric acid (UA) is commonly associated with gout and it is also a known cardiovascular disease risk factor. In contrast to such deleterious effects, UA possesses neuroprotective properties in the brain and elucidating the molecular mechanisms involved may have significant value regarding the therapeutic treatment of neurodegenerative disease. However, it is not yet fully established how UA levels are regulated in the brain.

Macrophage migration inhibitory factor is a possible candidate for the induction of microalbuminuria in diabetic db/db mice.

Preventing the onset of microalbuminuria in diabetic nephropathy is a problem that needs urgent rectification. The use of a mouse model for diabetes is vital in this regard. For example, db/db mice exhibit defects in the leptin receptor Ob-Rb sub-type, while the ob/ob strain exhibits defects in the leptin ligand.

Mitochondria-type GPAT is required for mitochondrial fusion.

Glycerol-3-phosphate acyltransferase (GPAT) is involved in the first step in glycerolipid synthesis and is localized in both the endoplasmic reticulum (ER) and mitochondria. To clarify the functional differences between ER-GPAT and mitochondrial (Mt)-GPAT, we generated both GPAT mutants in C. elegans and demonstrated that Mt-GPAT is essential for mitochondrial fusion.

Intracellular phospholipase A1 and acyltransferase, which are involved in Caenorhabditis elegans stem cell divisions, determine the sn-1 fatty acyl chain of phosphatidylinositol.

Phosphatidylinositol (PI), an important constituent of membranes, contains stearic acid as the major fatty acid at the sn-1 position. This fatty acid is thought to be incorporated into PI through fatty acid remodeling by sequential deacylation and reacylation. However, the genes responsible for the reaction are unknown, and consequently, the physiological significance of the sn-1 fatty acid remains to be elucidated.