Donepezil-induced oligodendrocyte differentiation is mediated through estrogen receptors.

Loss of oligodendrocytes, the myelin-forming cells of the central nervous system, and subsequent failure of myelin development result in serious neurological disorders such as multiple sclerosis. Using primary mouse embryonic neural stem cells (NSCs), we previously demonstrated that donepezil, an acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease, stimulates the differentiation of NSCs into oligodendrocytes and neurons, albeit at the expense of astrogenesis. However, the precise mechanisms underlying donepezil-induced differentiation remain unclear.

Neuronal Ca -dependent activator protein 1 (NCDAP1) induces neuronal cell death by activating p53 pathway following traumatic brain injury.

Overactivation of N-methyl-d-aspartate glutamate receptors (NMDARs) after traumatic brain injury (TBI) contributes to excitotoxic cell death. The hyperactivation of NMDARs results in toxic levels of intracellular Ca and in the activation of p53-mediated apoptosis pathway. Neuronal Ca -dependent activator protein 1 (NCDAP1) was identified as an epileptogenic gene of unknown function in our laboratory.

Donepezil promotes differentiation of neural stem cells into mature oligodendrocytes at the expense of astrogenesis.

Oligodendrocytes are the myelin-forming cells of the central nervous system. Oligodendrocyte loss and failure of myelin development result in serious human disorders, including multiple sclerosis. Previously, using oligodendrocyte progenitor cells, we have shown that donepezil, which is an acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease, stimulates myelin gene expression and oligodendrocyte differentiation.

The crucial role of Erk2 in demyelinating inflammation in the central nervous system.

Background: Brain inflammation is a crucial component of demyelinating diseases such as multiple sclerosis. Although the initiation of inflammatory processes by the production of cytokines and chemokines by immune cells is well characterized, the processes of inflammatory aggravation of demyelinating diseases remain obscure. Here, we examined the contribution of Erk2, one of the isoforms of the extracellular signal-regulated kinase, to demyelinating inflammation.

A novel strategy for selective gene delivery by using the inhibitory effect of blue light on jetPRIME-mediated transfection.

Photodynamic control of gene delivery is a new technology with growing applications in gene therapy and basic cell research. Main approaches of light-selective gene delivery rely on the light-dependent enhancement of transfection efficiency. Studies focused on light-stimulated inhibitory regulation of transfection have rarely been reported.

Nicotinic acetylcholine receptors mediate donepezil-induced oligodendrocyte differentiation.

Oligodendrocytes are the myelin-forming cells of the central nervous system (CNS). Failure of myelin development and oligodendrocyte loss results in serious human disorders, including multiple sclerosis. Here, we show that donepezil, an acetlycholinesterase inhibitor developed for the treatment of Alzheimer's disease, can stimulate oligodendrocyte differentiation and maturation of neural stem cell-derived oligodendrocyte progenitor cells without affecting proliferation or cell viability.

ERK1 and ERK2 are required for radial glial maintenance and cortical lamination.

ERK1/2 is involved in a variety of cellular processes during development, but the functions of these isoforms in brain development remain to be determined. Here, we generated double knockout (DKO) mice to study the individual and combined roles of ERK1 and ERK2 during cortical development. Mice deficient in Erk2, and more dramatically in the DKOs, displayed proliferation defects in late radial glial progenitors within the ventricular zone, and a severe disruption of lamination in the cerebral cortex.

Pulmonary blast injury in mice: a novel model for studying blast injury in the laboratory using laser-induced stress waves.

Background And Objectives: Primary blast injury is produced by shock waves. Blast injuries to lungs are extremely critical threats to survival, but their etiology is largely undefined. The majority of animal models for these injuries use explosive or complex experimental settings, limiting the laboratory study of blast injury.

ERK2 dependent signaling contributes to wound healing after a partial-thickness burn.

Burn healing is a complex physiological process involving multiple cell activities, such as cell proliferation, migration and differentiation. Although extracellular signal-regulated kinases (ERK) have a pivotal role in regulating a variety of cellular responses, little is known about the individual functions of ERK isoform for healing in vivo. This study investigated the role of ERK2 in burn healing.

Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice.

Background: Neonatal exposure to anesthetics that block N-methyl-D-aspartate receptors and/or hyperactivate gamma-aminobutyric acid type A receptor has been shown to cause neuronal degeneration in the developing brain, leading to functional deficits later in adulthood. The authors investigated whether exposure of neonatal mice to inhaled sevoflurane causes deficits in social behavior as well as learning disabilities.

Methods: Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h.

Analysis of extracellular signal-regulated kinase 2 function in neural stem/progenitor cells via nervous system-specific gene disruption.

Extracellular signal-regulated kinase 2 (ERK2) is involved in a variety of cell fate decisions during development, but its exact role in this process remains to be determined. To specifically focus on the role of ERK2 in the brain, and to avoid early lethalities, we used a conditional gene-targeting approach to preferentially inactivate Erk2 in the embryonic mouse brain. The resulting mutant mice were viable and were relatively normal in overall appearance.

Induction of cell migration of neural progenitor cells in vitro by alpha-1 adrenergic receptor and dopamine D1 receptor stimulation.

The radial migration is an important process in the development of the cerebral cortex. Earlier studies have reported that classical neurotransmitters such as L-dopamine and L-adrenaline regulate the proliferation of neural progenitor cells. We examined whether L-dopamine and L-adrenaline regulate cell migration, using embryonic neural progenitor cells from mouse embryonic telencephalon in vitro.

Extracellular signal-regulated kinase 2 (ERK2) knockdown mice show deficits in long-term memory; ERK2 has a specific function in learning and memory.

The extracellular signal-regulated kinase (ERK) 1 and 2 are important signaling components implicated in learning and memory. These isoforms display a high degree of sequence homology and share a similar substrate profile. However, recent findings suggest that these isoforms may have distinct roles: whereas ERK1 seems to be not so important for associative learning, ERK2 might be critically involved in learning and memory.

Effectiveness of narrow-band ultraviolet-B phototherapy for prevention of intimal hyperplasia in a rat carotid balloon injury model.

Background And Objective: Narrow-band ultraviolet-B light (NBUVB) (313 nm) is known to have anti-proliferative effects, implying a potential treatment for intimal hyperplasia, but it remains to be ascertained. We assessed the effects of NBUVB irradiation for prevention of intimal hyperplasia.

Study Design/materials And Methods: The rat carotid arteries were irradiated with NBUVB after balloon injury (BI), and the degree of intimal hyperplasia was histopathologically assessed.

Dopamine D2 receptor stimulation promotes the proliferation of neural progenitor cells in adult mouse hippocampus.

We initially examined the effects of apomorphine in vitro using mouse embryonic and adult neural progenitor cells. The effects of apomorphine treatment led to dose-dependent increases in the number of embryonic and adult neural progenitor cells, and dopamine D2 receptor antagonist treatment significantly reduced the increases induced by apomorphine. Next, we investigated the effects of apomorphine in vivo in the adult mouse hippocampus.

A single amino-acid change in ERK1/2 makes the enzyme susceptible to PP1 derivatives.

We generated extracellular signal-regulated kinase 1/2 (ERK1/2) mutants by introducing a single amino-acid substitution in subdomain V of the catalytic domain and then examined the susceptibility of these mutants to PP1 derivatives originally designed as Src inhibitors. Substituting smaller amino acids (alanine [Ala (A)] or glycine [Gly (G)]) for glutamine [Gln (Q)] in subdomain V drastically increased the susceptibility of ERK1/2 to 1-naphthyl PP1 (1NA-PP1). Wild-type ERK1/2 was resistant to 1NA-PP1 inhibition.

Targeted DNA transfection into the mouse central nervous system using laser-induced stress waves.

We investigated the feasibility of gene transfer into the mouse central nervous system (CNS) by applying nanosecond pulsed laser-induced stress waves (LISWs). Intraventricular or hippocampal injection of a reporter gene [enhanced green fluorescent protein (EGFP)] followed by application of LISWs showed this method to be efficient in the CNS of newborn and adult mice. Cells expressing EGFP reside at least 3.

Interaction of NF-Y with the 3'-flanking DNA sequence of the CCAAT box.

NF-Y, also referred to as CCAAT-binding factor, is a major CCAAT-binding transcription factor. The present study demonstrated that the 3'-flanking region of the CCAAT box is involved in the formation of a stable NF-Y.DNA complex.

Identification of a C-terminal region that is required for the nuclear translocation of ERK2 by passive diffusion.

Extracellular signal-regulated kinase 2 (ERK2) is located in the cytoplasm of resting cells and translocates into the nucleus upon extracellular stimuli by active transport of a dimer. Passive transport of an ERK2 monomer through the nuclear pore is also reported to coexist. We attempted to characterize the cytoplasmic retention and nuclear translocation of fusion proteins between deletion and site-directed mutants of ERK2 and green fluorescent protein (GFP).