Cannabinoids exert pleiotropic actions in the CNS, including inhibition of inflammatory responses and enhancement neuronal survival after injury. Although cannabinoid receptors are distributed widely brain, their presence has not been investigated previously oligodendrocytes. This study examined expression type 1 (CB1) rat oligodendrocytes vivo culture explored biological function. Expression CB1 by was demonstrated immunocytochemically postnatal adult white matter as well oligodendrocyte...

Prostaglandin E2 receptors (EP) were detected by radioligand binding in nuclear fractions isolated from porcine brain and myometrium. Intracellular localization immunocytofluorescence revealed perinuclear of EPs cerebral microvascular endothelial cells. Nuclear association EP1 was also found fibroblast Swiss 3T3 cells stably overexpressing human embryonic kidney 293 (Epstein-Barr virus-encoded antigen) expressing fused to green fluorescent protein. High-resolution immunostaining their...

The effects of prostaglandin E₂are thought to be mediated via G protein-coupled plasma membrane receptors, termed EP. However recent data implied that prostanoids may also act intracellularly. We investigated if the ubiquitous EP₃ and EP₄ receptors are localized in nuclear membranes. Radioligand binding studies on isolated fractions neonatal porcine brain adult rat liver revealed presence EP₄. A perinuclear localization EP_3α...

Although the steps involved in biosynthesis and secretion of neuropeptide vasopressin (AVP) have been extensively studied, factors which regulate AVP gene expression remain unknown. Therefore, we sought to determine dynamics mRNA accumulation response a strong stimulus for release, i.e. during salt imbibition ensuing period rehydration. levels were determined terms absolute amounts by novel quantitative densitometric hybridization assay, using vitro synthesized sense-strand RNA as standard...

We previously reported that the precursor form of nerve growth factor (pro-NGF) and not mature NGF is liberated in CNS an activity-dependent manner, its maturation degradation occur extracellular space by coordinated action proteases.Here, we present evidence diminished conversion pro-NGF to greater Alzheimer disease (AD) brain samples compared with controls. These alterations metabolic pathway likely resulted increased levels. The was largely a peroxynitrited AD samples. Intrahippocampal...

Multiple sclerosis (MS) lesions feature demyelination with limited remyelination. A distinct injury phenotype of MS features dying back oligodendrocyte (OL) terminal processes, a response that destabilizes myelin/axon interactions. This oligodendrogliopathy has been linked local metabolic stress, similar to the penumbra ischemic/hypoxic states. Here, we developed an in vitro model using human CNS-derived OLs and related this their bioenergetic properties. We determined energy utilization...

Abstract Insulin‐like growth factor‐1 (IGF‐1) interacts with the Type I receptor to activate two main signaling pathways, mitogen‐activated protein kinase (MEK)‐extracellular signal‐regulated (ERK) and phosphatidylinositol 3‐kinase (PI3K)‐Akt cascades, which mediate proliferation or survival of oligodendrocyte (OL) progenitors (OLPs). In other cellular systems, mammalian target rapamycin (mTOR) p70 S6 are downstream effectors that phosphorylate translation initiation factors (e.g. eIF‐4E),...

The biochemical development of rotation-mediated aggregating brain cell cultures was studied in a serum-free chemically defined medium the presence (complete medium) or absence triiodothyronine (T3). expression 2'',3''-cyclic nucleotide 3''-phosphodiesterase (CNP) and myelin basic protein (MBP), two components, temporally dissociated grown complete medium. CNP increased from day 8 reached plateau around 25. MBP accumulated rapidly third until fourth week culture. total content gradually...

PRMT5 is a type II protein arginine methyltranferase that catalyzes monomethylation and symmetric dimethylation of residues. functionally involved in variety biological processes including embryo development circadian clock regulation. However, the role oligodendrocyte differentiation central nervous system myelination unknown. Here we show expression gradually increases throughout postnatal brain development, coinciding with period active myelination. was observed neurons, astrocytes,...

Using a video-imaging technique, we characterized the effects of 8-isoprostaglandin F 2α (8-iso-PGF ) on retinal vasculature from piglets. 8-Iso-PGF potently contracted (EC 50 = 5.9 ± 0.5 nM) vessels. These were completely antagonized by cyclooxygenase inhibitor indomethacin, thromboxane synthase blocker CGS-12970, receptor antagonist L-670596, and putative non-voltage-dependent receptor-operated Ca 2+ pathway SKF-96365; constrictor 8-iso-PGF also partly attenuated ET A -receptor BQ-123 an...

Abstract Insulin‐like growth factor‐I (IGF‐I) is required for the of oligodendrocytes, although underlying mechanisms are not fully understood. Our aim was to investigate role phosphatidylinositol 3‐kinase (PI3K), mitogen‐activated protein kinase (MEK1), and Src family tyrosine kinases in IGF‐I‐stimulated proliferation oligodendrocyte progenitors. IGF‐I treatment increased cultured progenitors as determined by measuring incorporation [ 3 H]‐thymidine bromodeoxy‐uridine (BrdU). stimulated a...

Dehydration represents a strong stimulus for the secretory activity of hypothalamic vasopressinergic neurons and induces sustained rise in [Arg8]vasopressin (AVP) mRNA. We now report that, addition to change mRNA accumulation, this leads an increase size mature AVP gene transcripts. Using Northern blot analysis conjunction with internal RNA markers, we demonstrate here that 6-day period salt imbibition induced gradual from 810 maximum 930 bases. This was fully reversed by day 30 following...

Abstract Endocannabinoids have recently emerged as instructive cues in the developing central nervous system, and, based on expression of their receptors, we identified oligodendrocytes potential targets these molecules. Here, show that enzymes responsible for synthesis endocannabinoid 2‐arachidonoylglycerol (2‐AG), diacylglycerol lipase alpha (DAGLα) and beta (DAGLβ), degradation, monoacylglycerol (MAGL), can be found at different developmental stages. Moreover, cultured oligodendrocyte...

FTY720 is a sphingosine 1-phosphate receptor (S1PR) modulator used as daily therapy to reduce disease activity in the relapsing form of multiple sclerosis (MS). readily accesses CNS. Previous studies have shown that phosphorylated (FTY720-p) enhances oligodendrocyte progenitor cell (OPC) survival, differentiation, and remyelination following experimentally induced demyelination rodents. To elucidate underlying mechanism, human fetal OPCs alone or co-culture with rat dorsal root ganglia...

Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, respiratory activity human adult brain-derived is lower more predominantly glycolytic compared differentiated vitro from post natal rat brain oligodendrocyte progenitor cells. In response sub-lethal stress, reduce overall energy production rate impacting capacity...

Abstract The molecular mechanisms underlying AMPA (α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate) receptor‐mediated excitotoxicity were characterized in rat oligodendrocyte progenitor cultures. Activation of receptors, the presence cyclothiazide to selectively block desensitization, produced a massive Ca 2+ influx and cytotoxicity which blocked by antagonists CNQX GYKI 52466. A role for free radical generation cell death was deduced from three observations: (i) treatment with agonists...

Abstract The molecular mechanisms underlying H 2 O ‐induced toxicity were characterized in rat oligodendrocyte cultures. While progenitor cells more sensitive than mature oligodendrocytes to , the antioxidant, N ‐acetyl‐ l ‐cysteine, blocked at both stages of development. Differentiated contained glutathione did progenitors and less susceptible decreases concentration induced by stress. As free radicals have been considered serve as second messengers, we examined effect on activation...

Abstract Treatment of primary cultures oligodendrocyte precursors with calyculin A, a potent inhibitor protein phosphatases 1 and 2A, caused the phosphorylation two intermediate filament components, nestin vimentin. Phosphoamino acid analysis demonstrated that took place mainly on serine to lesser extent threonine residues. In addition, A treatment shift in distribution proteins from Triton‐X‐100 insolube fraction detergent soluble as by immunoblotting. This redistribution, which was evident...