Biomedical subjects

L Domenici

Publications and source records attributed to L Domenici.

At least 37 records · Page 2Linked to original sources

PubMed1998

The effects of anti-nerve growth factor monoclonal antibodies on developing basal forebrain neurons are transient and reversible.

In order to reassess the role of nerve growth factor (NGF) on rat basal forebrain cholinergic neurons (BFCNs) survival and/or phenotype maturation during the early postnatal life, we immunoneutralized NGF in vivo. Hybridoma cells producing the neutralizing anti-NGF monoclonal antibody alphaD11 were implanted in the lateral ventricle of the rat at different postnatal ages (P2, P8 and P15) and the effects on the number and the soma size of cholinacetyltransferase (ChAT) positive neurons were analysed 1, 2 or 3 weeks after the injection. A marked decrease in the number and in the soma size of BFCNs was observed implanting hybridoma cells at P2 and performing the analysis 1 week later. These effects are reversed 3 weeks after the implant of hybridoma cells at P2. At this time point, the levels of alphaD11 antibodies in the brain parenchyma are still in a vast molar excess over endogenous NGF. No effects on BFCNs were observed implanting alphaD11 cells at P15 while LGN neurons showed marked shrinkage. Our results demonstrate that the reduction in the number of ChAT-positive neurons during the first two postnatal weeks of anti-NGF treatment is not due to cell death. We conclude that NGF is not a survival factor for BFCNs, and that the influence of NGF on BFCNs cell maturation during the first 2 postnatal weeks is transient and reversible. Our results on tyrosine kinase (Trk) coexpression, suggest that NGF may cooperate with other factors in the cholinergic phenotype differentiation and maintenance after the second postnatal week.

Age Factors↗

PubMed1997

A critical period in the sensitivity of basal forebrain cholinergic neurones to NGF deprivation.

Cholinergic neurones of basal forebrain (BF) express receptors for nerve growth factor (NGF) and are sensitive to NGF. In many CNS structures, including the BF region, the expression of NGF and its receptors is developmentally regulated. To test whether BF neurones depend on NGF during restricted time windows of postnatal development, we antagonized endogenous NGF by implanting, in the lateral ventricle of the rat, hybridoma cells producing blocking antibodies specific for NGF. Implants were performed at postnatal day 2 (P2), P8 and P15. BF cholinergic neurones were drastically reduced in number only when endogenous NGF was antagonized during the first postnatal week. We conclude that BF cholinergic neurones are sensitive to NGF deprivation only during early postnatal development.

Animals↗

PubMed1996

The distribution of brain-derived neurotrophic factor and its receptor trkB in parvalbumin-containing neurons of the rat visual cortex.

We analysed the distribution of brain-derived neurotrophic factor (BNDNF) and its receptor trkB in the adult rat visual cortex, paying particular attention to a GABAergic neuronal subpopulation - the parvalbumin-positive cells. We found expression of trkB in the cell body and apical dendrite of pyramidal neurons and in the cell body of non-pyramidal neurons. Double labelling experiments revealed extensive colocalization of parvalbumin and trkB immunoreactivity in non-pyramidal neurons. Interestingly, the trkB-positive pyramidal neurons appeared surrounded by parvalbumin-labelled boutons. The use of double immunohistochemistry and in situ hybridization histochemistry showed that parvalbumin-positive neurons express trkB mRNA. BDNF mRNA was found in several cells. Coexpression of BDNF mRNA and parvalbumin immunoreactivity was extremely rare. These data strongly suggest that BDNF synthesized by cortical neurons acts as a postsynaptically derived factor for parvalbumin-positive neurons in the adult rat visual cortex.

Animals↗

PubMed1995

Patterns of synaptic activity in forward and feedback pathways within rat visual cortex.

1. The laminar and temporal distribution of synaptic activity supplied by forward and feedback connections between different areas of rat visual cortex was determined with the use of current source density (CSD) analysis in in vitro slices. In forward connections, synaptic potentials were evoked by electrically stimulating area 17 and recording in the extrastriate area LM (lateromedial), that ranks at the second hierarchical level, one step above primary visual cortex. For activating feedback connections, the location of stimulating and recording electrodes was reversed. 2. The synaptic interactions in reciprocal intracortical circuits are excitatory, and they are mediated through glutamate receptors that are blocked by kynurenic acid. 3. Forward connections from area 17 to area LM provide input to all layers including a strong input to layer 4. In contrast, feedback input to layer 4 is weak and is mainly directed to superficial and deep layers. This laminar distribution closely resembles that seen anatomically. 4. Both forward and feedback connections evoke distinct temporal patterns of synaptic activation in different layers. Although onset and peak latencies are slightly shorter in the forward than in the feedback pathway, the difference is not statistically significant. 5. The spatiotemporal distribution of synaptic activation by forward connections resembles the pattern evoked by geniculocortical inputs. Feedback connections show greater similarities to long-range connections within area 17, although they are not identical. Our results support the notion derived from anatomic and in vivo physiological studies that forward and feedback pathways belong to functionally distinct cortical circuits.

Animals↗

PubMed1995

Involvement of interstitial cells in endotoxin-induced acute lung injury. A histochemical and electron microscopical study.

Instillation of endotoxin into the rat trachea causes a disease representative of the lung response to several types of inflammatory injury and--in part--of human acute respiratory distress syndrome. Oxidizing radicals, including nitric oxide (NO), may be suspected to play some role in these conditions. The participation of leukocytes to tissue damage in these conditions has been reported, but the behaviour of lung interstitial cells in unknown. In this study, we have investigated on possible sources of NO and the response of lung interstitial cells during endotoxin-induced experimental lung injury. Rats were subjected to intratracheal instillation of endotoxin (5 mg/kg body weight) and sacrificed after 12, 24 and 48 h; animals treated with saline or sham-operated were used as controls. Analyses included conventional light microscopy, histochemical detection of NADPH-diaphorase (which co-localizes with NO synthase) and electron microscopy. Lung infiltrates appeared after 12 h and became progressively more severe up to 48 h. NADPH-diaphorase positive cells appeared in the septa after 24 h and became more numerous after 48 h; their nuclei were smooth-surfaced and the cytoplasm often extended into projections. By electron microscopy, only interstitial fibroblasts had a morphology similar to that of NO synthase positive cells and increased in number in the septa at the same time. These cells formed incomplete cuffs around blood capillaries and became large and rich in endoplasmic reticulum, as compared to those of the controls. These data suggest that hypertrophic fibroblastic interstitial cells can concur to maintain capillaries dilated (by NO secretion) and impair respiratory gas diffusion (by intervening between capillaries and pneumocytes), during experimental acute respiratory distress in the rat.

Animals↗

PubMed1994

Antibodies to nerve growth factor (NGF) prolong the sensitive period for monocular deprivation in the rat.

Neural plasticity in the visual cortex, as tested by changes in its functional organization induced by monocular deprivation (MD), is present only during a restricted period of postnatal development (critical period). To investigate whether this process of synapse strengthening depends upon NGF, we antagonized endogenous NGF during the critical period by implanting anti-NGF producing cells. Anti-NGF treated and control rats were monocularly deprived after the end of the critical period. In anti-NGF treated but not in control rats MD was still effective. We conclude that antagonism of endogenous NGF prolongs the critical period, possibly by delaying the process of synapse consolidation in the visual cortex.

Animals↗

PubMed1994

Monoclonal antibodies to nerve growth factor affect the postnatal development of the visual system.

Exogenous supply of nerve growth factor (NGF) prevents the effects of monocular deprivation. This suggests that visual afferents may be competing for an endogenous neurotrophic factor, related to NGF, whose production by postsynaptic cells depends on the activity of afferent fibers. To test the hypothesis that endogenous NGF may play a role in the functional and anatomical development of the rat geniculo cortical system, the physiological action of NGF in the rat visual system was antagonized by using two independent monoclonal antibodies which neutralize NGF (alpha D11 and 4C8). To provide a continuous supply of antibodies during the period of visual cortical plasticity, alpha D11 or 4C8 antibody-producing hybridoma cells were implanted in the lateral ventricle of rats at postnatal day 15. This resulted in dramatic alterations of two of the most important parameters characterizing the functional development of the visual system, namely, visual acuity and binocularity of cortical neurons and in shrinkage of cells in the lateral geniculate nucleus. This demonstrates that the action of endogenous NGF is necessary for the normal functional and anatomical development of the geniculocortical system.

Animals↗

PubMed1994

Functional postnatal development of the rat primary visual cortex and the role of visual experience: dark rearing and monocular deprivation.

Postnatal development of rat visual cortical functions was studied by recording extracellularly from the primary visual cortex of 22 animals ranging in age from postnatal day 17 (P17) to P45. We found that in the youngest animals (P17-P19) all visual cortical functions tested were immature. Selectivity for orientation and movement direction of visual stimuli was almost absent, most cells received binocular input and their mean receptive field size was 5-6 times the adult size. Visual acuity was half its adult value. These functional properties developed gradually during the following weeks and by P45 they were all adult-like. This functional development is affected by manipulations of the visual input such as dark rearing (DR) and monocular deprivation (MD). DR prevented the normal postnatal maturation of visual cortical functions: in P60 rats, dark reared from birth, their visual cortical functions resembled those of P19-P21 rats. MD from P15 to P45 resulted in a dramatic shift of the ocular dominance distribution (ODD) in favour of the open eye and in a loss of visual acuity for the deprived eye. To determine the sensitive period of rat visual cortex to MD (critical period) we evaluated the shift in ODD of visual cortical neurones in rats that were subjected to the progressive delay of the onset of fixed MD period (10 days). Our results show that the critical period begins around the end of the third postnatal week, peaks between the fourth and fifth week and starts to decline from the end of the fifth week.

Age Factors↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

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

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1989

Changing distribution of GABA-like immunoreactivity in pigeon visual areas during the early posthatching period and effects of retinal removal on tectal GABAergic systems.

The distribution of GABA-like immunoreactivity in the pigeon visual system was studied during the first 9 days after hatching using a mouse monoclonal antibody, mAb 3A12, to glutaraldehyde linked GABA (Matute & Streit, 1986). GABA-like immunoreactivity was seen in cell bodies as well as in neuropil at the level of both the retina and central visual regions at any posthatching age. However, the distribution of putative GABAergic cells and processes varied with age reaching the adult pattern at around 9 days. As a general observation, almost no cell bodies in the retina (except for some perikarya in the ganglion cell layer) were labeled at hatching but densely packed immunostained processes were present in the inner plexiform layer. During the next few days, GABA-immunoreactive amacrine and horizontal cells appeared and the adult distribution of GABA-like immunoreactivity was reached at around 9 days. In the other visual regions examined, the general trend in the variation of GABA-like immunoreactivity included: (1) a progressive decrease in the density of immunostained cell bodies and (2) an almost parallel increase in the concentration of stained neuropil. Since in pigeons the adult organization of visual pathways and the final distribution of putative GABAergic systems are reached at around the same age, we suggest the possibility that incoming ganglion cell axons play a role in regulating the distribution of GABA-like immunoreactivity in visual areas. This hypothesis is supported by the fact that the distribution of GABA-like immunoreactivity in the superficial layers of the optic tectum was altered following ablation of the contralateral retina immediately after hatching.

Animals↗