Biomedical subjects

G Carmignoto

Publications and source records attributed to G Carmignoto.

7 recordsLinked to original sources

PubMed1992

Activity-dependent decrease in NMDA receptor responses during development of the visual cortex.

Plasticity of the developing visual system has been regarded as the best model for changes of neuronal connections under the influence of the environment. N-methyl-D-aspartate (NMDA) receptors are crucial for experience-dependent synaptic modifications that occur in the developing visual cortex. NMDA-mediated excitatory postsynaptic currents (EPSCs) in layer IV neurons of the visual cortex lasted longer in young rats than in adult rats, and the duration of the EPSCs became progressively shorter, in parallel with the developmental reduction in synaptic plasticity. This decrease in NMDA receptor-mediated EPSC duration is delayed when the animals are reared in the dark, a condition that prolongs developmental plasticity, and is prevented by treatment with tetrodotoxin, a procedure that inhibits neural activity. Application of L-glutamate to outside-out patches excised from layer IV neurons of young, but not of adult, rats activated prolonged bursts of NMDA channel openings. A modification of the NMDA receptor gating properties may therefore account for the age-dependent decline of visual cortical plasticity.

Action Potentials↗

PubMed1992

Distribution of protein gene product 9.5 (PGP 9.5) in the vertebrate retina: evidence that immunoreactivity is restricted to mammalian horizontal and ganglion cells.

Using light microscopic immunocytochemistry, we have studied the distribution of protein gene product 9.5 (PGP 9.5), a neuron-specific protein first extracted from human brain (Doran et al., '83:J. Neurochem. 40:1542-1547), in the vertebrate retina. Retinas were obtained from frog, chicken, rat, rabbit, cow, cat, dog, and human. No immunoreactivity was observed in frog and only a faint staining was present in chicken. In mammalian retinas, a strong positive reaction was restricted to horizontal and ganglion cells, with minor interspecies variations. Immunostaining was present throughout the cell body and the dendritic tree in horizontal cells. At the level of retinal ganglion cells, immunolabel was particularly abundant in cell bodies and axons forming the optic nerve. Only the main dendrites were stained, the remainder of the dendritic tree giving rise to a diffuse punctate reaction in the inner plexiform layer. In rats, displaced amacrine cells, which are known to contribute largely (40-50%) to the total neuronal population within the ganglion cell layer (Perry, '81: Neuroscience 6:931-944) were not immunoreactive, as demonstrated from (i) analysis of the morphology, cell size and cell density of immunoreactive neurons in wholemounts; (ii) colocalization of retrograde label and PGP 9.5 immunoreactivity in about 80% of ganglion cells after injection of peroxidase into the optic nerve; and (iii) reduction of immunoreactivity in the inner plexiform and ganglion cell layers following optic nerve transection. Western blot analysis of extracts from rabbit retinas indicated that the immunoreactive species is PGP 9.5 or a closely related molecule. Recent studies have demonstrated that PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase (Wilkinson et al., '89:Science 246:670-673). The present results, therefore, suggest that differences in the ubiquitination process exist between retinal neurons.

Animals↗

PubMed1992

N-methyl-D-aspartate-induced neurotoxicity in the adult rat retina.

The present study provides evidence that the adult mammalian retina is highly sensitive to the excitotoxic action of NMDA. In particular, we have investigated the effects of a single intravitreal injection of different doses of N-methyl-D-aspartate (NMDA) (2-200 nmoles) on the adult rat retina. Morphological evaluation of transverse sections of retinae demonstrated a dose-dependent loss of cells in the ganglion cell layer (GCL) and a reduction in the thickness of the inner plexiform layer. No obvious alterations were noted in the more distal retinal layers. Quantitative analyses of Nissl-stained whole-mounted retinae revealed that administration of 20 nmoles of NMDA resulted in a 70% loss of cells with a soma diameter greater than 8 microns (presumed retinal ganglion cells); a 20% loss of cells with a soma diameter smaller than 8 microns (presumed displaced amacrine cells) was also observed. In addition, NMDA produced a dose-dependent decrease of retinal choline acetyltransferase (ChAT) activity, suggesting that NMDA affects cholinergic amacrine cells as well. MK-801, a non-competitive NMDA antagonist, completely prevented the NMDA-induced loss of cells in the GCL and blocked, in a dose-dependent manner, the NMDA-induced decrease of ChAT activity. The excitotoxic action of NMDA observed in these experiments is thus likely mediated through the NMDA receptor subtype. This "in vivo" model may be utilized to identify potential drugs that antagonize or limit the deleterious effects consequent to NMDA receptor overstimulation in the central nervous system.

Animals↗

PubMed1991

Nerve growth factor prevents the amblyopic effects of monocular deprivation.

Monocular deprivation early in life causes dramatic changes in the functional organization of mammalian visual cortex and severe reduction in visual acuity and contrast sensitivity of the deprived eye. We tested whether or not these changes could be from competition between the afferents from the two eyes for a target-derived neurotrophic factor. Rats monocularly deprived during early postnatal development were treated with repetitive intraventricular injections or topical administration of nerve growth factor. The effects of monocular deprivation were then assessed electrophysiologically. In untreated animals visual acuity and contrast sensitivity of the deprived eye were strongly reduced, whereas in nerve growth factor-treated animals these parameters were normal.

Amblyopia↗

PubMed1991

Expression of NGF receptor and NGF receptor mRNA in the developing and adult rat retina.

Nerve growth factor (NGF) has been recently found to rescue axotomized retinal ganglion cells (RGCs) of the adult rat from degeneration. Because the trophic effect of NGF involves a receptor-coupling event, the characterization and cellular localization of the NGF receptor (NGFR) in the retina are essential to understanding the possible specific action of NGF in this district of the central nervous system. We report here that the NGFR mRNA is expressed in fetal, neonatal, and adult rat retina. Using monoclonal antibody 192-IgG to immunoprecipitate and immunohistochemically identify NGFR, we also found that the NGFR from the retina has a molecular weight identical to that of the NGFR from PC12 cells. The NGFR is localized on RGCs and Müller cells. Finally, following ligation of the optic nerve, NGFR-immunopositive material was found to accumulate both distal and proximal to the site of ligation, suggesting that RGC axons anterogradely and retrogradely transport the NGFR. These data raise the possibility that NGF may play a specific role in rat RGCs.

Adrenal Gland Neoplasms↗

PubMed1990

Schwann cells promote the survival of rat retinal ganglion cells after optic nerve section.

Schwann cells (SCs) are known to play an important role for the regeneration of mammalian peripheral nerves. Their effect is likely due to the production of neuronotrophic and/or supportive factors. Here we study the effect of intraocular transplant of SCs on the survival of rat retinal ganglion cells (RGCs) after the intracranial section of the optic nerve. SCs were injected intraocularly in adult hooded rats. Surviving RGCs were retrogradely labeled with horseradish peroxidase applied to the proximal stump of the optic nerve. Results show that intraocular transplants of SCs promote the survival of a large number of RGCs for periods as long as 9 and 14 weeks after optic nerve section. In experimental retinae, surviving RGCs were 2- to 8-fold more numerous than in controls. This finding suggests that SCs are the source of factors that promote the survival of RGCs. Nerve growth factor is produced by SCs, and the intraocular injection of nerve growth factor has been previously shown to promote RGC survival. The rescuing effect of SCs on RGCs is greater than that obtained by intraocular injection of nerve growth factor. This greater effect may be due to the action of other neurotrophic factors produced by SCs or by transplanted SCs producing NGF in a sustained fashion.

Animals↗

PubMed1989

Effect of NGF on the survival of rat retinal ganglion cells following optic nerve section.

The ability of NGF (2.5S subunit) to support the survival of adult rat retinal ganglion cells (RGCs) and optic nerve fibers after intracranial section of the optic nerve was investigated. NGF was injected intraocularly at a dose of 3 micrograms/injection every 2.3 d from the day of axotomy to analysis. Control animals received cytochrome c injections. The survival of RGCs was analyzed in whole-mounted retinas after either cresyl violet staining or labeling with HRP applied to the proximal stump of the optic nerve. Survival times were 5 and 7 weeks. Diameter distribution and number of myelinated optic nerve fibers were assessed in ultrathin cross sections of the optic nerve. We found that RGCs surviving axotomy were much more numerous following NGF treatment compared with controls. Large-size cells were, in particular, preserved by NGF treatment. The quantitative ultrastructural studies indicated that the number of myelinated optic nerve fibers at 5 and 7 weeks postaxotomy was significantly greater in the NGF group with respect to the cytochrome c group. In agreement with the results obtained at the level of the RGCs, large-diameter axons were, in particular, preserved. We conclude that NGF injected intraocularly is effective in promoting the survival of RGCs and optic nerve fibers at least for a period as long as 7 weeks after intracranial section of the optic nerve.

Animals↗