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Biomedical subjects

L Maffei

Publications and source records attributed to L Maffei.

At least 73 records · Page 4Linked to original sources

Monocular deprivation effects in the rat visual cortex and lateral geniculate nucleus are prevented by nerve growth factor (NGF). I. Visual cortex.

The effects of monocular deprivation done during the critical period are usually ascribed to competition between the two sets of monocular thalamic afferents taking place at cortical level. We have suggested that loss in competition for the deprived eye is explained by the lack of a neurotrophic factor, produced in the cortex and dependent on electrical activity. To test this hypothesis we have exogenously supplied nerve growth factor (NGF) to rats monocularly deprived (MD) during the critical period, and studied whether monocular deprivation still affected the functional and anatomical organization of the visual cortex. NGF is produced in the rat visual cortex during the critical period, and its expression, at least in the hippocampus, seems to be regulated by electrical activity. Ocular dominance distribution of area 17 neurons, visual acuity, and Parvalbumin immunoreactivity (Parva-LI) were determined in four sets of animals: normal rats, control untreated monocularly deprived rats, deprived rats treated with cytochrome c (to control for non-specific aspects of NGF treatment), and deprived rats treated with NGF. Parva-LI is an excellent marker for the effects of monocular deprivation on the functional organization of the rat visual cortex. We found that exogenous supply of NGF completely prevented the shift in ocular dominance distribution of visual cortical neurons, the loss of visual acuity for the deprived eye, and the strong reduction in Parva-LI induced by monocular deprivation in control rats.

Acetylcholinesterase↗

Monocular deprivation effects in the rat visual cortex and lateral geniculate nucleus are prevented by nerve growth factor (NGF). II. Lateral geniculate nucleus.

In the preceding paper (Berardi et al. Proc. R. Soc. Lond. B 251, 17 (1993)), it has been shown that nerve growth factor (NGF) prevents the functional and anatomical alterations induced by monocular deprivation (MD) at the level of the visual cortex. Here we report that an exogenous supply of NGF prevents the shrinkage of neurons in the deprived laminae of lateral geniculate nucleus (LGN). The soma size distribution for the deprived ipsilateral laminae of MD rats is shifted towards smaller sizes (mean percentage of shrinkage with respect to the ipsilateral undeprived lamina = 21%, s.d. = 2%). As in other mammals, MD affects LGN relay neurons and spares LGN neurons projecting to the monocular portion of primary visual cortex. In NGF-treated animals we found that the soma size distributions for the deprived and undeprived ipsilateral laminae extensively overlap. The results of the two papers show that an exogenous supply of NGF prevents MD effects at both levels, visual cortex and LGN, and suggest a role for NGF in the plasticity of the geniculo-cortical pathway.

Animals↗

Effects of nerve growth factor on neuronal plasticity of the kitten visual cortex.

1. The effect of intraventricular administration of nerve growth factor (NGF) by means of a cannula-minipump system was studied in kittens monocularly deprived during the critical period. The ocular dominance of area 17 neurones of NGF-treated and control kittens was determined by conventional extracellular recordings. The soma size of cells in A and A1 laminae of the lateral geniculate nucleus (LGN) was also evaluated in Cresyl Violet preparations. 2. Binocularly responsive neurons were found to be significantly more numerous in NGF-treated than in control kittens. The shrinkage of cells from the deprived LGN laminae normally observed in control kittens was prevented by NGF administration. 3. Following an initial period of monocular deprivation (MD) kittens subsequently treated with NGF showed a substantial recovery of functional binocular connections. 4. These findings indicate that the administration of NGF during the period of deprivation reduces the amblyopic effects of MD, while its administration to kittens with both eyes open following the initial deprivation promotes recovery of the deprived eye. 5. Neurotrophic factors may contribute to the regulation of experience-dependent modifications of synaptic connectivity in the visual cortex.

Amblyopia↗

Simultaneous occurrence of monoclonal gammopathy and acute secondary leukemia with overexpression of P-glycoprotein.

A 52-year-old woman, previously treated with chemo- and radiotherapy for Hodgkin's disease, developed an acute non-lymphoid leukemia and, contemporarily, an IgG-kappa paraproteinemia. Cytogenetic analysis showed a major clone, representing 90% of observed metaphases, with monosomy of chromosomes 5 and 14. In addition, leukemic cells exhibited a high expression of the P-glycoprotein, a transmembrane glycoprotein involved in the multidrug-resistance mechanism. Possible explanations for this cluster of findings are provided.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Protein-DNA interactions in the 5'-flanking region of the bovine pancreatic ribonuclease gene.

In the 5'-flanking region of the bovine pancreatic ribonuclease gene a sequence has been identified which specifically binds one or more factors present in nuclear protein extracts prepared from bovine pancreas. The binding site, as delineated by footprinting analysis, is located in a region extending from positions -113 to -146 relative to the transcription initiation site of the ribonuclease gene. This region contains consensus sequences for known control transcriptional elements. The observed pattern of protein-DNA interactions is likely to be pancreas-specific as it could not be detected with nuclear extracts prepared from HeLa or bovine aorta endothelium cells.

Animals↗

Exogenous supply of nerve growth factor prevents the effects of strabismus in the rat.

It has recently been reported that exogenous supply of nerve growth factor prevents the effects of monocular deprivation both in rats and in cats. Here we have extended these experiments to the case of strabismus. Repeated intraventricular injections of nerve growth factor were performed in rats made surgically strabismic early in the critical period. At the end of the critical period the ocular dominance distribution of visual cortical neurons was assessed in strabismic untreated, strabismic nerve growth factor-treated and strabismic Cytochrome C-treated (control) rats by means of extracellular recordings. We found that in rats surgical strabismus causes a consistent loss of binocular neurons. By contrast the treatment with nerve growth factor maintains the normal ocular dominance distribution of neurons in the primary visual cortex. We conclude that nerve growth factor exogenously supplied prevents the effects induced by surgical strabismus in rats and suggest that nerve growth factor has a role in visual cortical plasticity.

Animals↗

Parvalbumin immunoreactivity: a reliable marker for the effects of monocular deprivation in the rat visual cortex.

In mammals, monocular deprivation performed during the early stages of postnatal development (critical period) dramatically affects the functional organization of the visual cortex. Since the early work of Hubel and Wiesel, the effects of monocular deprivation are accounted for by the fibers driven by the two eyes competing for the control of cortical territories. In cat and monkey striking structural changes accompany the functional effects of monocular deprivation. Also, in the rat, monocular deprivation causes functional alteration at the level of visual cortex; no structural correlates of these effects, however, have so far been described. Parvalbumin is a calcium binding protein that in the neocortex colocalizes with a subpopulation of GABAergic neurons. Here we report that in the rat monocular deprivation results in a dramatic reduction of parvalbumin-like immunoreactivity in the visual cortex contralateral to the deprived eye. This effect is due to competitive phenomena and not to visual deprivation itself, it is restricted to the binocular portion of the visual cortex and neither binocular deprivation, nor dark rearing can induce it. We conclude that parvalbumin-like immunoreactivity is a useful immunohistochemical marker for the effects of monocular deprivation in the rat visual cortex.

Animals↗

Nerve growth factor (NGF) prevents the shift in ocular dominance distribution of visual cortical neurons in monocularly deprived rats.

The hypothesis that NGF could play a role in the plasticity of the developing mammalian visual cortex was tested in monocularly deprived (MD) rats. In particular, we have asked whether an exogenous supply of NGF could prevent the changes in ocular dominance distribution induced by monocular deprivation. Hooded rats were monocularly deprived for 1 month, starting at postnatal day 14 (P14), immediately before eye opening, by means of eyelid suture. In eight rats, only monocular deprivation was performed; in eight rats, monocular deprivation was combined with intraventricular injections of beta-NGF, and in three rats, with intraventricular injections of cytochrome C. Injections (2 microliters) were given every other day for a period of 1 month. Single neuron activity was recorded in the primary visual cortex of MD rats, MD rats treated with NGF, and MD rats treated with cytochrome C at the end of the deprivation period, and in normal rats of the same age. We found that monocular deprivation caused a striking change in the ocular dominance distribution of untreated MD rats, reducing binocular cells by a factor of two and increasing by a factor of eight the number of cells dominated by the nondeprived eye. In MD NGF-treated rats, the ocular dominance distribution was indistinguishable from the normal. Cytochrome C treatment was completely ineffective in preventing the ocular dominance shift induced by monocular deprivation. To test whether NGF affected cortical physiology or interfered with transmission of visual information, we evaluated in NGF-treated rats the spontaneous discharge and the orientation selectivity. We found these functional properties to be in the normal range. We conclude that NGF is effective in preventing the effects of monocular deprivation in the rat visual cortex and suggest that NGF is a crucial factor in the competitive processes leading to the stabilization of functional geniculocortical connections during the critical period.

Animals↗

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↗

Different effects of intracranial and intraorbital section of the optic nerve on the functional responses of rat retinal ganglion cells.

A lesion to the optic nerve of adult mammals leads to the retrograde degeneration and finally to the death of injured retinal ganglion cells. In this study, we have evaluated the effects induced by different sites of axotomy on the functional changes occurring in the retinal ganglion cells after optic nerve section. We have investigated the functional properties of retinal ganglion cells of adult rats by recording the retinal responses to patterned stimuli (pattern electroretinogram) after unilateral section of the optic nerve at two different levels: intraorbital and intracranial. The results show that the site of lesion of the optic nerve affects the time of disappearance of the pattern electroretinogram. The pattern electroretinogram takes longer to be degraded after an intracranial section than an intraorbital section.

Animals↗

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↗

Transplant of embryonal nervous tissue preserves the responses of rat retinal ganglion cells after section of the optic nerve.

We have investigated the effectiveness of embryonal tectal tissue transplants in preserving the physiological activity of lesioned ganglion cells by recording the visual responses from the adult rat retina after section of the optic nerve, with or without transplants of embryonal nervous tissue on the stump. We have found that transplant of embryonal nervous tissue at the level of the optic nerve section has dramatic effects in preserving visual retinal responses to patterned stimuli for times as long as five months after surgery. By this time retinal responses to patterned stimuli have almost completely disappeared in control animals with optic nerve section alone.

Action Potentials↗

Monocular deprivation in split-chiasm kittens does not impair the development of visuo-motor behaviour.

Development of visual acuity is known to be impaired by early monocular deprivation. This may be due to lack of visual experience or to abnormal binocular competition. We report here the results of behavioural experiments on monocularly deprived kittens in which the optic chiasm had been split. In these kittens it has been found that visual acuity of the deprived eye is as good as the visual acuity of the non-deprived eye, namely 2-2.5 c/deg.

Animals↗

Pattern ERG in rats following section of the optic nerve.

The aim of this study is to investigate in the rat the properties of the pattern electroretinogram (ERG) and to assess whether it depends upon the functional integrity of ganglion cells. Flash and pattern ERG were recorded from urethane anaesthetized hooded rats. The pattern ERG was evoked by phase alternating gratings of various spatial frequencies and contrasts. In the first part of the study we determined how the amplitude of the main harmonic of the pattern ERG (2nd harmonic) varies as a function of stimulus parameters such as spatial and temporal frequency, contrast and mean luminance. In the second part of the study we investigated the effects of the retrograde degeneration of ganglion cells following optic nerve section on the amplitude of pattern ERG. We found that the section of the optic nerve leads to the progressive disappearance of the P-ERG which is almost complete 4 months after surgery. By this time only few axotomized ganglion cells are left. The flash ERG remained unaffected. Thus, the pattern electroretinogram seems to be a simple and sensitive tool to investigate the functional integrity of retinal ganglion cells in rats.

Animals↗

The visual acuity of the lynx.

Visual evoked potentials were recorded from the occipital scalp of two anaesthetized Lynx (Lynx europea) in response to alternating gratings of various spatial frequencies and contrasts. The visual acuity of the Lynx was found to be around 5-6 c/deg, i.e. very close to the visual acuity of the cat and by far inferior to human acuity.

Animals↗

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↗

Correlation in the discharges of neighboring rat retinal ganglion cells during prenatal life.

The spontaneous discharges of neighboring retinal ganglion cells were recorded simultaneously in anesthetized prenatal rats between embryonic days 18 and 21. We report here that in the majority of cases the firings of neighboring retinal ganglion cells are strongly correlated during prenatal life. Correlation in the discharges of neighboring cells during development has long been suggested as a way to consolidate synaptic connections with a target cell onto which they converge, a model first proposed by Hebb. Correlation in the activities of neighboring neurons in the retina could be the basis of developmental processes such as refinement of retinotopic maps in the brain and segregation of the inputs from the two eyes.

Animals↗