Biomedical subjects

A Cellerino

Publications and source records attributed to A Cellerino.

At least 19 recordsLinked to original sources

PubMed2003

Psychobiology of facial attractiveness.

The last decade has witnessed an upsurge of interest in the research on facial attractiveness. The development of computer graphics has allowed to objectively investigate the conserved features of attractive faces. Averageness, symmetry and sex-specific traits have been associated with attractiveness. The effect of averageness is exemplified by blending a set of real faces into a chimeric face. This composite is more attractive than most of the faces used to create it. Beautiful faces are not simply average faces, however. If the female-specific features of a female composite face are enhanced, the resulting face is perceived as more attractive than the composite. In particular, smaller than average chin, smaller than average nose and higher than average forehead, all are traits associated with female's attractiveness. These traits have been interpreted as signs of high estrogen/testosterone ratio and therefore cues of high fertility. However, these same traits are also a species-specific characteristic of Homo sapiens that differentiates it from other hominid species. Preference for caricature of human features could represent a relic of species recognition mechanisms. Female preferences for male faces proved to be more variable than male preferences for female faces. Different facial traits are preferred in the choice of short-term and long-term partners. Preference for short term depend on the hormonal status and changes across the menstrual cycle and is influenced by contraceptive hormonal treatment. Psychological factors are also important sources of variance: female preferences correlate with self-perceived attractiveness, status in a relationship and degree of gender-conformity.

Beauty↗

PubMed2000

The dynamics of neuronal death: a time-lapse study in the retina.

Using time-lapse video microscopy, we have followed the process of neuronal death in an intact region of the mammalian nervous system. We show here the fast dynamics of nuclear fragmentation, which is over in <1 hr for neurons undergoing apoptosis in the living rat retina. Nuclear fragmentation is accompanied by a progressive raise of intracellular calcium and followed by erratic movement of the apoptotic cells, documenting their loss of adhesion.

Amidines↗

PubMed2000

Apoptosis in the developing visual system.

Programmed cellular death is a widespread phenomenon during development of the nervous system. Two classes of molecules are particularly important in the context of apoptosis control in the nervous system: intracellular effectors homologous to the Caenorhabditis elegans Ced-3, -4, and -9 proteins, which in mammals correspond to the proteases of the caspase family, Apaf-1, and the members of the Bcl-2 protein family, and neurotrophic factors. Retinal ganglion cells lend a convenient model system with which to investigate apoptosis in central neurons during development as well as after injury. In this review, we discuss the role of these molecules in the control of programmed cellular death in the retinotectal system. Transgenic animal models and expression studies have shown that caspases, Bcl-2, Bax, and possibly Bcl-X are necessary players for the control of programmed cellular death in retinal ganglion cells. Bax and caspase 3 expression in retinal ganglion cells is upregulated after injury, and inhibition of Bax or caspase 3 increases the survival of injured retinal ganglion cells. Neurotrophins can support the survival of injured retinal ganglion cells, but this effect is transient. The physiological role of neurotrophins in the development of the retinocollicular system seems more related to the topographic refinement of retinocollicular projections, a process that is mediated, at least partially, by selective elimination of retinal ganglion cells making inappropriate topographic projections.

Animals↗

PubMed2000

Retinal ganglion cells with NADPH-diaphorase activity in the chick form a regular mosaic with a strong dorsoventral asymmetry that can be modelled by a minimal spacing rule.

We have identified a class of retinal ganglion cells in the chick retina that can be labelled by NADPH-diaphorase histochemistry. These cells have a remarkable topographic distribution, being restricted to the dorsal hemiretina, and form a highly regular mosaic, as revealed by the analysis of nearest neighbour distribution and Delaunay triangulation. Autocorrelation analysis of the mosaic of NADPH-diaphorase-positive retinal ganglion cells shows that the mosaic spatial organization could be generated with the single constraint that two elements cannot be closer than a given minimal distance (d(min)), which we confirmed by computer simulations. In contrast with what has been observed in other mosaics, here d(min) varies with cell density. However, the observed variation of the exclusion area is consistent with an original assembly of the mosaic with a constant d(min) (as is the case in other mosaics), followed by differential expansion of the retina during development.

Animals↗

PubMed1999

Retinal ganglion cell loss after the period of naturally occurring cell death in bcl-2-/- mice.

Over-expression of Bcl-2 is known to reduce the extent of retinal ganglion cell death during development as well as after axotomy. Here we investigated whether retinal ganglion cell (RGC) numbers are reduced in mice with a targeted inactivation of the bcl-2 gene. Compared with wild-type mice, adult bcl-2 null mutants have lost 29% of the retinal ganglion cell axons in the optic nerve. This reduction was almost fully established at P15, but not present at P10, which marks the end of the period of naturally occurring cell death. These observations, together with the previously reported late loss of primary motoneurons and peripheral neurons, point to a general physiological requirement for Bcl-2 soon after the period of naturally occurring cell death.

Aging↗

PubMed1999

Excess target-derived brain-derived neurotrophic factor preserves the transient uncrossed retinal projection to the superior colliculus.

During early postnatal development, a widespread ipsilateral projection to the superior colliculus is secondarily restricted to a small topographically defined region by elimination of ipsilaterally projecting retinal ganglion cells. Brain-derived neurotrophic factor (BDNF) has been proposed as the target-derived neurotrophic factor for retinal ganglion cells in several studies. Here we investigated the long-term effects of excess BDNF in the retinal ganglion cell target on naturally occurring retinal ganglion cell (RGC) elimination and on the restriction of the ipsilateral projection. To this end, sustained overexpression of BDNF was achieved in the postnatal superior colliculus using an adenoviral vector. While the total number of retinal ganglion cells in the adenovirus-BDNF treated animals was unchanged, a much higher proportion of RGCs retained a projection to the ipsilateral superior colliculus. We conclude that an excess of target-derived BDNF does not reduce the net amount of naturally occurring cell death in the retino-collicular system, but prevents the negative selection of retinal ganglion cells making inappropriate topographic connections.

Adenoviruses, Human↗

PubMed1999

Effects of brain-derived neurotrophic factor on the development of NADPH-diaphorase/nitric oxide synthase-positive amacrine cells in the rodent retina.

Amacrine neurons expressing nitric oxide synthase (NOS) contain brain-derived neurotrophic factor (BDNF) receptors and respond to exogenous BDNF [Klöcker, N., Cellerino, A. & Bähr, M. (1998) J. Neurosci., 18, 1038-1046]. We analysed the effects of BDNF on the development of neurons which express NOS in the mouse and rat retina. Rat pups received a total of three intraocular injections of BDNF at intervals of 48 h, starting at postnatal day 16 (P16), and were killed at P22. The retinas were stained for NADPH-diaphorase, a histological marker of NOS. NOS-expressing neurons were found in both the inner nuclear layer (INL) and the ganglion cell layer (GCL). Two classes of NOS-expressing neurons, type I and type II, had already been distinguished in the INL [Koistinaho, J. & Sagar, S.M. (1995) In Osborne, N.N. & Chader, G.J. (eds), Progress in Retinal and Eye Research, Vol. 15. Oxford University Press, pp. 69-87] and a third one in the GCL. Up-regulation of NADPH-diaphorase activity was observed after BDNF treatment. The number of type I neurons remained stable, whereas the number of type II neurons and NOS-positive neurons in the GCL increased significantly (P < 0.001). Type I and type II neurons were significantly larger in BDNF-treated retinas. Double-labelling experiments revealed that BDNF induces NADPH-diaphorase in dopaminergic neurons and amacrine cells displaced to the GCL, but not in retinal ganglion cells. In mice homozygous for a null mutation of the bdnf gene, the intensity of NADPH-diaphorase labelling in both somata and processes was reduced, but the number of labelled neurons was not dramatically reduced. These findings indicate that BDNF regulates the neurotransmitter phenotype of NOS-expressing amacrine neurons under physiological conditions, but is not required for their survival.

Animals↗

PubMed1998

Brain-derived neurotrophic factor modulates the development of the dopaminergic network in the rodent retina.

Dopaminergic cells in the retina express the receptor for brain-derived neurotrophic factor (BDNF) (). To investigate whether BDNF can influence the development of the retinal dopaminergic pathway, we performed intraocular injections of BDNF during the second or third postnatal week and visualized the dopaminergic system with tyrosine hydroxylase (TH) immunohistochemistry. Both regimens of BDNF treatment caused an increase in TH immunoreactivity in stratum 1 and stratum 3 of the inner plexiform layer (IPL). D2 dopamine receptor immunoreactivity, a presynaptic marker of dopaminergic cells (), was also increased in stratum 1 and stratum 3 of the inner plexiform layer. These data suggest that BDNF causes sprouting of dopaminergic fibers in the inner plexiform layer. Other neurochemical systems, for example, the cholinergic amacrine cells, remained unaffected. Similar effects were observed after injections of neurotrophin-3 and neurotrophin-4, but not nerve growth factor. Analysis of whole-mounted TH-immunolabeled retinae revealed hypertrophy of dopaminergic cells (+41% in soma areas; p < 0.01) and an increase of labeled dopaminergic varicosities in stratum 1 of the IPL (+51%; p < 0.01) after BDNF treatment. The opposite was observed in mice homozygous for a null mutation of the bdnf gene: dopaminergic cells were atrophic (-22.5% in soma areas; p < 0.05), and the density of TH-positive varicosities in stratum 1 was reduced (57%; p < 0.01). We conclude that BDNF controls the development of the retinal dopaminergic network and may be particularly important in determining the density of dopaminergic innervation in the retina.

Animals↗

PubMed1998

Free radical scavenging and inhibition of nitric oxide synthase potentiates the neurotrophic effects of brain-derived neurotrophic factor on axotomized retinal ganglion cells In vivo.

Brain-derived neurotrophic factor (BDNF) partially promotes the survival of axotomized retinal ganglion cells (RGCs). In analogy with in vitro experiments (; ), we tested whether neuroprotection by BDNF is limited by adverse effects as a consequence of excessive free radical formation. First, we investigated whether BDNF and the free radical scavenger N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN) cooperate in protecting RGCs from axotomy-induced death. Although systemic S-PBN treatment alone did not influence RGC survival after axotomy, it potentiated the neuroprotective effects of BDNF significantly. Single BDNF treatment rescued 27% of the RGCs, which otherwise would have died 14 d after optic nerve transection, whereas a combined treatment of BDNF and S-PBN improved this rescue rate up to 68%. We then investigated whether the adverse effects of BDNF could be ascribed to activation of nitric oxide synthase (NOS). We found colocalization of NOS and the BDNF receptor TrkB in the retina. NADPH-diaphorase reactivity, a reliable marker for NOS in the rat retina, increased after chronic BDNF treatment in vivo. Systemic application of the NOS-inhibitor N-omega-nitro-L-arginine-methylester (L-NAME) potentiated the neuroprotective action of BDNF (55% rescue rate). We conclude that activation of NOS is a pathological consequence of BDNF application, which reduces its neuroprotective potential. The observation that this adverse effect can be antagonized by systemic application of free radical scavengers could be of relevance for clinical applications of neurotrophins in human neurodegenerative diseases.

Animals↗

PubMed1997

Brain-derived neurotrophic factor/neurotrophin-4 receptor TrkB is localized on ganglion cells and dopaminergic amacrine cells in the vertebrate retina.

The tyrosine kinase TrkB is a receptor for the neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). Retinal ganglion cells are responsive to BDNF, and TrkB has been localized in ganglion cells as well as in a subpopulation of amacrine cells in the retina of the chicken and the rat. In the present paper, we analyzed the distribution of TrkB immunoreactivity in the retina of marmoset monkeys, ferrets, rabbits, rats, mice, chickens, pigeons, barn owls, Pseudemys turtles, Xenopus frogs, goldfishes, and carps. TrkB antibodies gave a positive reaction in all of these vertebrates. TrkB immunoreactivity was detected in the majority of retinal ganglion cells. Some amacrine cells also contained TrkB immunoreactivity; they were located mainly at the vitreal border of the inner nuclear layer, and their relative abundance varied in the different species. Until now, no information has been available concerning the neurochemical identity of the amacrine neurons containing TrkB. In some species (marmoset monkeys, rats, pigeons), we observed that the morphology and location of TrkB-immunoreactive amacrine cells was reminiscent of that of the well-described dopaminergic cells. To determine whether dopaminergic amacrine cells contained TrkB immunoreactivity, we therefore performed double-labelling immunohistochemistry by using tyrosine hydroxylase (TH) antibodies in combination with TrkB antibodies in marmoset monkeys, rats, pigeons, Pseudemys turtles, and goldfishes. The most novel finding of the present paper is that, in all of these species, the majority of dopaminergic neurons were found to contain TrkB immunoreactivity. Dopaminergic neurons, on the other hand, represented only a fraction of the TrkB+ amacrine cells. Our data suggest that BDNF and/or NT-4 might modulate expression of TH in the retina and may therefore influence the retinal dopaminergic system. Whatever the action of TrkB ligands on the retinal dopaminergic system, it was conserved during vertebrate evolution.

Animals↗

PubMed1997

Reduced size of retinal ganglion cell axons and hypomyelination in mice lacking brain-derived neurotrophic factor.

While brain-derived neurotrophic factor (BDNF) delays the death of axotomized retinal ganglion cells in rodents, it is unclear if it affects any aspect of the normal development of these cells. Here we examined the optic nerve of bdnf-/- mice. Axonal numbers were normal, but their diameter, as well as the proportion of myelinated axons, was reduced at postnatal day 20 (P20). In contrast, the facial nerve was not hypomyelinated. Expression levels of mRNAs coding for the myelin proteins PLP and MBP were substantially reduced in the hippocampus and cortex at P20, but not in the sciatic nerve. Intraventricular injections of BDNF into the ventricles of wild-type mice at P10 and P12 up-regulated expression of PLP in the hippocampus at P14. These results indicate a role of BDNF, discussed as indirect, in the control of myelination in the central nervous system.

Animals↗

PubMed1996

Brain-derived neurotrophic factor promotes the differentiation of various hippocampal nonpyramidal neurons, including Cajal-Retzius cells, in organotypic slice cultures.

Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system, where its function is poorly understood. The aim of this study was to investigate the effects of BDNF on the differentiation of hippocampal nonpyramidal neurons using organotypic slice cultures prepared from postnatal rats. The application of BDNF induced an increase in immunostaining for the microtubule-associated protein (MAP)-2 in non-pyramidal neurons of the stratum oriens. BDNF promotes the elongation of the dendrites of these neurons, as demonstrated by analysis after biocytin labeling. Calbindin-D- and calretinin-containing subgroups of nonpyramidal cells in the stratum oriens were responsive to BDNF but not to nerve growth factor, as shown by an increase in the number of neurons immunostained for these proteins. BDNF also induced an increase in neuropeptide Y immunostaining of stratum oriens neurons. In contrast, BDNF had no effect on parvalbumin immunostaining, despite the fact that these cells express the BDNF receptor trkB. In addition, BDNF increased calretinin immunoreactivity in Cajal-Retzius cells situated around the hippocampal fissure. The Cajal-Retzius neurons persisted in slices beyond the time at which they degenerate in vivo. However, BDNF is not required for the survival of these cells, because they also persisted in slices from BDNF knock-out mice. The present results indicate that BDNF exerts an effect on the morphology of stratum oriens nonpyramidal cells and their calcium-binding protein levels. BDNF also regulates the calretinin content of Cajal-Retzius cells but is not necessary for their survival.

Animals↗

PubMed1996

The action of neurotrophins in the development and plasticity of the visual cortex.

Nerve growth factor (NGF) and the other members of the NGF gene family have been extensively characterized as neurotrophic factors. Recently a modulatory action of these neurotrophic factors on synapse efficacy has emerged. The developing visual system has provided a convenient model to test the role of neurotrophins on neural plasticity in vivo.

Animals↗

PubMed1996

Expression of messenger RNA coding for the nerve growth factor receptor trkA in the hippocampus of the adult rat.

Nerve growth factor is a member of the neurotrophin gene family and acts as a neurotrophic factor on a variety of neuronal populations. Nerve growth factor biological action is mediated by binding to the transmembrane tyrosine kinase trkA, although the low affinity neurotrophin receptor p75 may also play a role. TrkA messenger RNA in the central nervous system is localized within a small number of specific neuronal populations, as opposed to the widespread expression of the other members of the trk family, trkB and trkC. In particular, cholinergic neurons of the basal forebrain, the prototype of nerve growth factor-sensitive neurons in the brain express trkA. Several lines of evidence indicate that other populations of central neurons, in particular hippocampal neurons, may be responsive to nerve growth factor as well. In fact, nerve growth factor rescues hippocampal neurons from ischemic cell death in vivo and increases neurotransmitter release from hippocampal neurons in culture. Moreover, nerve growth factor has been implicated in spatial learning, a process known to be dependent on the hippocampal formation. The following paper reports expression of trkA messenger RNA in the rat hippocampus by in situ hybridization and reverse transcription-polymerase chain reaction. This finding supports the notion of hippocampal neurons as an nerve growth factor-sensitive population.

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↗

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↗

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↗