Glial-derived neurotrophic factor upregulates expression of functional SNS and NaN sodium channels and their currents in axotomized dorsal root ganglion neurons.
AuthorsCummins TR, Black JA, Dib-Hajj SD, Waxman SG
JournalJ Neurosci
PubMed ID11102483
'Dorsal root ganglion (DRG) neurons produce multiple sodium currents, including several different TTX-sensitive (TTX-S) currents and TTX-resistant (TTX-R) currents, which are produced by distinct sodium channels. We previously demonstrated that, after sciatic nerve transection, the levels of SNS and NaN sodium channel alpha-subunit transcripts and protein in small (18-30 micrometer ... More
Role of p38 mitogen-activated protein kinase in axotomy-induced apoptosis of rat retinal ganglion cells.
AuthorsKikuchi M, Tenneti L, Lipton SA
JournalJ Neurosci
PubMed ID10864961
'p38 is a member of the mitogen-activated protein (MAP) kinase superfamily and mediates intracellular signal transduction. Recent studies suggest that p38 is involved in apoptotic signaling in several cell types, including neurons. In the mammalian retina, approximately 50% of the retinal ganglion cells (RGCs) die by apoptosis during development. Additionally, ... More
Fluoro-Gold: An alternative viability stain for multicolor flow cytometric analysis.
AuthorsBarber L, Prince HM, Rossi R, Bertoncello I
JournalCytometry
PubMed ID10404151
'BACKGROUND: The viability stains propidium iodide (PI) and 7-amino-actinomycin D (7-AAD) are excited at 488 nm, as are the commonly used antibody conjugates fluorescein isothiocyanate (FITC), phycoerythrin (PE), and cyanine 5 dye covalently coupled to R-phycoerythrin (RPE-Cy5). When excited by a single laser, spectral overlap in the emission of PI ... More
Nitric oxide induces pathological synapse loss by a protein kinase G-, Rho kinase-dependent mechanism preceded by myosin light chain phosphorylation.
The molecular signaling that underpins synapse loss in neuropathological conditions remains unknown. Concomitant upregulation of the neuronal nitric oxide (NO) synthase (nNOS) in neurodegenerative processes places NO at the center of attention. We found that de novo nNOS expression was sufficient to induce synapse loss from motoneurons at adult and ... More
Depression of retinal glutamate transporter function leads to elevated intravitreal glutamate levels and ganglion cell death.
AuthorsVorwerk CK, Naskar R, Schuettauf F, Quinto K, Zurakowski D, Gochenauer G, Robinson MB, Mackler SA, Dreyer EB
JournalInvest Ophthalmol Vis Sci
PubMed ID11006260
PURPOSE: Elevated levels of extracellular glutamate have been implicated in the pathophysiology of neuronal loss in both central nervous system and ophthalmic disorders, including glaucoma. This increase in glutamate may result from a failure of glutamate transporters (molecules that ordinarily regulate extracellular glutamate; E:xcitatory A:mino A:cid T:ransporter; EAAT). Elevated glutamate ... More
Retinal neuronal death induced by intraocular administration of a nitric oxide donor and its rescue by neurotrophic factors in rats.
AuthorsTakahata K, Katsuki H, Kume T, Nakata D, Ito K, Muraoka S, Yoneda F, Kashii S, Honda Y, Akaike A
JournalInvest Ophthalmol Vis Sci
PubMed ID12657619
PURPOSE: To investigate the neurotoxic outcome in the rat retina exposed to nitric oxide (NO) released from an NO donor and to evaluate the effects of neurotrophic factors on the survival of NO-damaged retinal cells. METHODS: An NO releasing compound, N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine (NOC 12), was intravitreously injected into a rat's ... More
Divergent NMDA signals leading to proapoptotic and antiapoptotic pathways in the rat retina.
AuthorsManabe S, Lipton SA
JournalInvest Ophthalmol Vis Sci
PubMed ID12506100
PURPOSE: To investigate the involvement of the p38 mitogen-activated protein (MAP) kinase and phosphatidylinositol-3 (PI-3) kinase-Akt signaling pathways after pathologic stimulation by N-methyl-D-aspartate (NMDA) receptors of retinal neurons in vivo. METHODS: NMDA (2-200 nmol), SB203580 (0.2-10 nmol, an inhibitor of p38 MAP kinase), LY294002 (6 nmol, an inhibitor of PI-3 ... More