Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by progressive loss of motor neurons (MNs) and subsequent muscle weakness. These pathological features are associated with numerous cellular changes, including alteration in mitochondrial morphology and function. However, the molecular mechanisms associating mitochondrial structure with ALS pathology are poorly understood.

Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis.

Interstitial fibrosis is a common feature of chronic kidney disease, and platelet-derived growth factor receptor-β (PDGFR-β)-positive mesenchymal cells are reportedly the major source of scar-producing myofibroblasts. We had previously demonstrated that albumin and its derivative R-III (a retinol-binding protein-albumin domain III fusion protein) inhibited the transdifferentiation/activation of hepatic stellate cells (HSCs) to myofibroblasts and that R-III administration reduced liver fibrosis. In this study, we isolated cells (referred to as renal stellate cells, RSCs) from rat kidney tissues using the HSC isolation protocol and compared their morphological and biochemical characteristics with those of HSCs.

Myelin degeneration induced by mutant superoxide dismutase 1 accumulation promotes amyotrophic lateral sclerosis.

Myelin is a specialized membrane that wraps around nerve fibers and is essential for normal axonal conduction in neurons. In the central nervous system, oligodendrocytes are responsible for myelin formation. Recent studies have reported pathological abnormalities in oligodendrocytes in human patients with amyotrophic lateral sclerosis (ALS) and a mouse model of ALS expressing the G93A mutation of the human superoxide dismutase 1 (mtSOD1).

Distribution and neuronal circuit of spexin 1/2 neurons in the zebrafish CNS.

Spexin (SPX) is a highly conserved neuropeptide that is widely expressed in mammalian brain and peripheral tissue. In teleost, SPX1 is mainly expressed in the brain and ovary, and is involved in reproduction and food intake. A second form of SPX, SPX2, was recently identified in chick, Xenopus, and zebrafish.

Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target.

To understand disease mechanisms, a large-scale analysis of human-yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human-yeast genetic interactions were identified by en masse transformation of the human disease genes into a pool of 4653 homozygous diploid yeast deletion mutants with unique barcode sequences, followed by multiplexed barcode sequencing to identify yeast toxicity modifiers.

Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records.

Prediction of new disease indications for approved drugs by computational methods has been based largely on the genomics signatures of drugs and diseases. We propose a method for drug repositioning that uses the clinical signatures extracted from over 13 years of electronic medical records from a tertiary hospital, including >9.4 M laboratory tests from >530,000 patients, in addition to diverse genomics signatures.

Protective effects of caffeic acid phenethyl ester (CAPE) against neomycin-induced hair cell damage in zebrafish.

Objective: Caffeic acid phenethyl ester (CAPE) is known to reduce the generation of oxygen-derived free radicals, which is a major mechanism of aminoglycoside-induced ototoxicity. The objective of the present study was to evaluate the effects of CAPE on neomycin-induced ototoxicity in zebrafish (Brn3c: EGFP).

Methods: Five-day post-fertilization zebrafish larvae (n=10) were exposed to 125 μM neomycin and one of the following CAPE concentrations for 1h: 50, 100, 250, 500, or 1000 μM.

Protective role of edaravone against neomycin-induced ototoxicity in zebrafish.

Aminoglycosides such as neomycin are one of the most commonly prescribed types of antibiotics worldwide. However, these drugs appear to generate free radicals within the inner ear, which can result in permanent hearing loss. We evaluated the effects of edaravone, a neuroprotective agent, on neomycin-induced ototoxicity in transgenic zebrafish.

Protective Role of Trimetazidine Against Neomycin-induced Hair Cell Damage in Zebrafish.

Objectives: Trimetazidine (TMZ) is known to reduce the generation of oxygen-derived free radicals. The objective of the present study was to evaluate the effects of TMZ on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP).

Methods: Five-day, postfertilization zebrafish larvae were exposed to 125 µM neomycin and one of the following TMZ concentrations for 1 hour: 10 µM, 100 µM, 500 µM, 1,000 µM, 1,500 µM, or 2,000 µM.

Protective role of NecroX-5 against neomycin-induced hair cell damage in zebrafish.

NecroX-5, one of the derivatives of NecroX series compounds, is a mitochondrial reactive oxygen species and reactive nitrogen species scavenger that inhibits cell death against various kinds of oxidative stresses. The objective of the present study was to evaluate the effects of NecroX-5 on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Five days post-fertilization, zebrafish larvae were exposed to 125 μM neomycin and one of the following NecroX-5 concentrations for 1 h: 10, 25, 50, and 75 μM.

Generation of demyelination models by targeted ablation of oligodendrocytes in the zebrafish CNS.

Demyelination is the pathological process by which myelin sheaths are lost from around axons, and is usually caused by a direct insult targeted at the oligodendrocytes in the vertebrate central nervous system (CNS). A demyelinated CNS is usually remyelinated by a population of oligodendrocyte progenitor cells, which are widely distributed throughout the adult CNS. However, myelin disruption and remyelination failure affect the normal function of the nervous system, causing human diseases such as multiple sclerosis.

Protective effects of edaravone against cisplatin-induced hair cell damage in zebrafish.

Objective: Edaravone is known to have a potent free radical scavenging effect. The objective of the present study was to evaluate the effects of edaravone on cisplatin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP).

Methods: Five day post-fertilization zebrafish larvae were exposed to 1000 μM cisplatin and 50 μM, 100 μM, 250 μM, 500 μM, 750 μM, and 1000 μM concentrations of edaravone for 4h.

Indian hedgehog B function is required for the specification of oligodendrocyte progenitor cells in the zebrafish CNS.

A subset of ventral spinal cord precursors, known as pMN precursor cells, initially generate motor neurons and then oligodendrocyte progenitor cells (OPCs), which migrate and differentiate as myelinating oligodendrocytes in the developing neural tube. The switch between motor neuron and oligodendrocyte production by the pMN neural precursors is an important step in building a functional nervous system. However, the precise mechanism that orchestrates the sequential generation of motor neurons and oligodendrocytes within the common population of pMN precursors is still unclear.

Antagonistic regulation of PAF1C and p-TEFb is required for oligodendrocyte differentiation.

Oligodendrocytes are myelinating glial cells in the CNS and are essential for proper neuronal function. During development, oligodendrocyte progenitor cells (OPCs) are specified from the motor neuron precursor domain of the ventral spinal cord and differentiate into myelinating oligodendrocytes after migration to the white matter of the neural tube. Cell cycle control of OPCs influences the balance between immature OPCs and myelinating oligodendrocytes, but the precise mechanism regulating the differentiation of OPCs into myelinating oligodendrocytes is unclear.

Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish.

Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation.

Microarray screening for genes involved in oligodendrocyte differentiation in the zebrafish CNS.

Within the vertebrate nervous system, myelination is required for the normal function of neurons by facilitating the rapid conduction of action potentials along axons. Oligodendrocytes are glial cells which myelinate axons in the central nervous system. Disruption of myelination and remyelination failure can cause human diseases such as multiple sclerosis.

Tcf3 function is required for the inhibition of oligodendroglial fate specification in the spinal cord of zebrafish embryos.

The generation of various subtypes of neurons and glial cells at the right time and place is crucial for the proper development of the vertebrate CNS. Although the mechanisms and factors for the regulation of neuronal diversity in the CNS have been well studied, the mechanisms regulating the sequential production of neuronal and glial cells from neural precursors remain poorly understood. This study shows that Tcf3, a member of the Lef/Tcf family of proteins, is required to inhibit the premature oligodendroglial fate specification of spinal cord precursors using the transgenic zebrafish, which expresses a dominant repressor form of Tcf3 under the control of a heat-shock inducible promoter.

Neuron-specific expression of atp6v0c2 in zebrafish CNS.

Vacuolar ATPase (V-ATPase) is a multi-subunit enzyme that plays an important role in the acidification of a variety of intracellular compartments. ATP6V0C is subunit c of the V(0) domain that forms the proteolipid pore of the enzyme. In the present study, we investigated the neuron-specific expression of atp6v0c2, a novel isoform of the V-ATPase c-subunit, during the development of the zebrafish CNS.

Visualization of myelination in GFP-transgenic zebrafish.

The insulation of axons in the vertebrate nervous system by myelin is essential for efficient axonal conduction. Myelination disruption and remyelination failure can cause human diseases, such as multiple sclerosis and hereditary myelin diseases. However, despite progress in understanding myelination regulation, many important questions remain unanswered.

Intravital imaging in zebrafish using quantum dots.

Background/aims: Fluorescent quantum dots (QDs) are powerful multipurpose interfaces of nanotechnology providing long-term and multicolor imaging of cellular and molecular interactions. The application of QDs in living organisms is just beginning to be explored, and zebrafish embryos may be suitable vertebrate model organisms for intravital imaging with QDs. To investigate their potential in skin research, we used QDs as microangiography contrast agents and attempted to visualize the cardiovascular system in zebrafish.

Notch-regulated perineurium development from zebrafish spinal cord.

In the developing central nervous system, nerve fascicles are surrounded by a protective sheath known as the perineurium. Perineurium is composed of perineurial cells that have both epithelial and myofibroblastoid properties, including tight and gap junctions and contractility. However, the molecular mechanism that governs perineurial development remains unclear.

Frizzled 8a function is required for oligodendrocyte development in the zebrafish spinal cord.

Oligodendrocytes are the myelinating cells in the central nervous system. The development of oligodendrocytes is mediated by complex signaling networks, including Wnt signaling. Although Wnt signaling has been studied in various aspects of neurogenesis, the distinct roles of various Frizzled receptors that mediate the Wnt signaling in the CNS remain virtually unknown.