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Biomedical subjects

G Carmignoto

Publications and source records attributed to G Carmignoto.

29 records · Page 2Linked to original sources

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↗

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↗

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↗

Flash and pattern electroretinograms during and after acute intraocular pressure elevation in cats.

Retinal functionality during short-term intraocular pressure (IOP) elevation and simultaneous systemic blood pressure (BP) variations was evaluated in the cat by recording the electroretinogram in response to both homogenous flickering light (FERG) and contrast reversing gratings (PERG). The mean arterial blood pressure (BPm) was pharmacologically adjusted to different levels and a large range of IOP values was tested. Results indicate that both FERG and PERG responses are impaired when the eye perfusion pressure (PP = BPm - IOP) is reduced and they disappear at a critical PP value of about 20 mm Hg, irrespective of the absolute value of the IOP. In addition, when the critical perfusion pressure is maintained for periods longer than 5 min, the recovery of the PERG response, when present, is always delayed compared to the full recovery of the FERG response. These findings support the hypothesis that vascular factors, ie, the impairment of the retinal blood supply, may be responsible for the disappearance of the retinal electrical activity during short-term IOP elevation. Furthermore, the retinal ganglion cells, presumably the main source of the PERG response, appear less likely to recover from the acute ischemic episode.

Acute Disease↗

Monocular deprivation in kittens differently affects crossed and uncrossed visual pathways.

The effects of monocular deprivation (MD) on the crossed and uncrossed visual projections were studied using both electrophysiological and behavioural criteria. Our results show that Visual Evoked Potentials (VEPs) from the deprived eye (DE) in response to contrast reversing gratings are more reduced in the ipsilateral than in the contralateral cortex. This suggests a different sensitivity of the crossed and uncrossed visual pathways to MD. In the behavioural experiments comparable findings were obtained.

Animals↗

Spatial-frequency characteristics of neurones of area 18 in the cat: dependence on the velocity of the visual stimulus.

The spatial and temporal response properties of neurones of areas 17 and 18 were studied in single units (165) of anaesthetized and paralysed cats. The visual stimuli were drifting or alternating gratings. We confirmed and extended the observation by Tolhurst & Movshon (1975) showing that the spatial-frequency characteristics of neurones of area 17 are largely independent of the temporal parameters of drifting or alternating gratings. The spatial-frequency tuning curves of neurones of area 18 shift along the spatial-frequency axis when the velocity or the temporal frequency of the drifting grating are changed. The effect of an increase either of velocity or temporal frequency is to shift the cell spatial-frequency tuning curve down the spatial-frequency scale, keeping relatively constant the strength and band width of the response. The spatial-frequency tuning curves of neurones of area 18 do not show this temporal-frequency-dependent phenomenon when the stimuli are gratings alternated in phase. In this case neurones of areas 17 and 18 show a similar behaviour. The response properties of neurones of area 18 are compared with recent psychophysical results obtained in similar experimental conditions. The hypothesis is advanced that both areas 17 and 18 are devoted to the processing of spatial information. Area 17 would be responsible for the processing of patterns in stationary or quasi-stationary situations while area 18 would be responsible for that of patterns moving at high velocities.

Animals↗

Can functional reorganization of area 17 following monocular deprivation be modified by GM1 internal ester treatment?

It has been extensively reported that monocular exposure early in life leads to profound alterations in visual cortical areas, where the majority of cells become responsive only to the stimulation of the normal eye. We have investigated a possible effect of the monosialoganglioside internal ester, termed AGF2, on the neuronal cortical plasticity of the kitten's visual cortex following monocular deprivation. Results indicate that in monocularly deprived kittens treated with ganglioside the ocular dominance shift in favor of the normal eye is partially prevented.

Animals↗

Muscle reinnervation--I. Restoration of transmitter release mechanisms.

Following sciatic nerve crush the restoration of neuromuscular transmission in the extensor digitorum longus muscle of rat proceeds in a well defined manner: (a) as soon as the nerve-muscle contact is reformed, a subthreshold end-plate potential is recorded; no 'non-transmitting stage' is observed; (b) 24 hours later muscle action potentials are induced by nerve stimulation; (c) miniature end-plate potentials are absent or very rare at the newly reinnervated end-plates; their frequency returns to normal in about 4 weeks; (d) the frequency is also very much reduced in 30 mM K+ and hypertonic solutions and recovers slowly, in 4 and 5 weeks, respectively, while black widow spider venom is from the beginning as powerful as in normal neuromuscular junctions; (e) at the early stages of reinnervation the Ca2+-dependent release mechanisms are much stronger than control cases, while the Ca2+-independent mechanisms are weaker and recover in 5 weeks. The gradual reassembly and restoration of neurotransmitter release mechanisms of the extensor digitorum longus nerve terminal indicate the complexity of pre-synaptic ending organization.

Animals↗

Muscle reinnervation--II. Sprouting, synapse formation and repression.

Extensor digitorum longus muscle is reinnervated by the regenerating neurites at the end-plate region; as soon as the contact is made, the rate of neurite elongation inside the cleft decreases about 1000-fold while interfibre growth and sprout formation proceed unchanged. Polyinnervation reaches the maximum level 7-10 days after reinnervation, then synaptic repression begins. The elimination of redundant innervation takes place when the biophysical properties of the muscle are again normal. There is no sign of either phagocytosis or degeneration, therefore the process of synaptic repression is probably due to retraction, as neurites do when in culture. The role of Schwann cells and nerve sheath in the process of maintenance is suggested.

Animals↗