Biomedical subjects

A Vallée

Publications and source records attributed to A Vallée.

At least 19 recordsLinked to original sources

PubMed1998

Serotonin axons of the neostriatum show a higher affinity for striatal than for ventral mesencephalic transplants: a quantitative study in adult and immature recipient rats.

We previously showed that grafts of fetal ventral mesencephalic tissue are practically not innervated by host serotonin (5-HT) axons after implantation into the striatum of rats aged more than 14 days, at variance with transplants of cortical or striatal tissue into the adult striatum, which are well innervated by these axons. Using 5-HT immunohistochemistry and in vitro [3H]5-HT uptake/autoradiography, we have examined and quantified the innervation of ventral mesencephalic versus striatal grafts several months after implantation into the striatum of neonatal (postnatal day 5 or P5), juvenile (P15), and adult rats. Ventral mesencephalic grafts implanted in P5 rats received a moderate 5-HT innervation, while similar grafts implanted in P15 or adult recipients were almost free of any 5-HT fibers (-80%, compared to P5). The density of 5-HT innervation showed a tendency toward higher values in striatal than in ventral mesencephalic grafts (1.6-2 times higher in P5 and adult recipients; 4 times higher in P15 recipients). The difference was more striking, and significant, when only the true striatal portions of the striatal grafts were considered, i.e., DARPP-32-immunopositive areas (4-5 times higher in P5 and adult recipients; 10 times higher in P15 recipients). Accordingly, these DARPP-32-positive areas were also more densely innervated than the DARPP-32-negative zones of the same grafts (3 times higher at any age). The 5-HT innervation density also decreased with increasing age of the recipients in DARPP-32-positive, as well as DARPP-32-negative compartments of the striatal grafts (-75% in adults), but this decrease appeared more gradual (-50% in juveniles) than with mesencephalic grafts. It is concluded that the 5-HT axons innervating the neostriatum have a better affinity for striatal grafts than for ventral mesencephalic grafts or the nonstriatal portions of striatal grafts. In adulthood, the relative affinity of these axons for the different types of grafts is maintained, even though their growth capacity decreases irrespective of the target tissue considered. This experimental model may prove useful for the identification of the receptors and ligands that are responsible for target recognition by 5-HT axons and to test the possibility that the progressive decrease of axonal growth capacity from neonatal age to adulthood be related to a downregulation of such molecules.

Aging↗

PubMed1998

Dystonin is essential for maintaining neuronal cytoskeleton organization.

The mouse neurological mutant dystonia musculorum (dt) suffers from a hereditary sensory neuropathy. We have previously described the cloning and characterization of the dt gene, which we named dystonin (Dst). We had shown that dystonin is a neural isoform of bullous pemphigoid antigen 1 (Bpag1) with an N-terminal actin-binding domain. It has been shown previously that dystonin is a cytoskeletal linker protein, forming a bridge between F-actin and intermediate filaments. Here, we have used two different antibody preparations against dystonin and detected a high-molecular-weight protein in immunoblot analysis of spinal cord extracts. We also show that this high-molecular-weight protein was not detectable in the nervous system of all dt alleles tested. Immunohistochemical analysis revealed that dystonin was present in different compartments of neurons--cell bodies, dendrites, and axons, regions which are rich in the three elements of the cytoskeleton (F-actin, neurofilaments, and microtubules). Ultrastructural analysis of dt dorsal root axons revealed disorganization of the neurofilament network and surprisingly also of the microtubule network. In this context it is of interest that we observed altered levels of the microtubule-associated proteins MAP2 and tau in spinal cord neurons of different dt alleles. Finally, dt dorsal root ganglion neurons formed neurites in culture, but the cytoskeleton was disorganized within these neurites. Our results demonstrate that dystonin is essential for maintaining neuronal cytoskeleton integrity but is not required for establishing neuronal morphology.

Animals↗

PubMed1998

beta-Actin is confined to structures having high capacity of remodelling in developing and adult rat cerebellum.

Neurons undergo complex morphological changes during differentiation and in cases of plasticity. A major determinant of cell morphology is the actin cytoskeleton, which in neurons is comprised of two actin isoforms, non-muscle gamma- and beta-actin. To better understand their respective roles during differentiation and plasticity, their cellular and subcellular localization was examined in developing and adult cerebellar cortex. It was observed that gamma-actin is expressed at a constant level throughout development, while the level of beta-actin expression rapidly decreases with age. At the light microscopic level, gamma-actin staining is ubiquitous and the only developmental change observed is a relative reduction of its concentration in cell bodies and white matter. In contrast, beta-actin staining almost completely disappears from the cytoplasm of cell bodies, primary dendrites and axons. In young cerebellar cultures, gamma-actin is found in the cell body, neurites and growth cones, while beta-actin is mainly found in growth cones, as previously reported in other primary neuronal culture systems [Kaech et al. (1997), J. Neuroscience, 17, 9565-9572; Bassell et al., (1998), J. Neuroscience, 18, 251-265]. Electron microscopy of post-embedding immunogold-labelled tissue confirms the widespread distribution of gamma-actin, and also reveals an increased concentration of gamma-actin in dendritic spines in the adult. During development, beta-actin accumulation is observed in actively growing structures, e.g., growth cones, filopodia, cell bodies and axonal tracts. In the adult cerebellar cortex, beta-actin is preferentially found in dendritic spines, structures which are known to retain their capacity for morphological modifications in the adult brain. This differential subcellular localization and developmental regulation of the two actin isoforms point to their different roles in neurons.

Actins↗

PubMed1997

Quantitative and morphometric data indicate precise cellular interactions between serotonin terminals and postsynaptic targets in rat substantia nigra.

We have quantified the density of serotonin axonal varicosities, their synaptic incidence and their distribution among potential targets in the pars reticulata and pars compacta of the rat substantia nigra. Serotonin axonal varicosities, counted at the light microscopic level following in vitro [3H]serotonin uptake and autoradiography, amounted to 9 x 10(6)/mm3 in the pars reticulata and 6 x 10(6)/mm3 in the pars compacta, among the densest serotonin innervations in brain. As determined at the electron microscopic level following immunolabelling for serotonin, virtually all serotonin varicosities in the pars reticulata and 50% of those in the pars compacta formed a synapse, essentially with dendrites. The combination of serotonin immunocytochemistry with tyrosine hydroxylase immunolabelling of dopamine neurons reveals that 20% of the serotonin synaptic contacts in the pars reticulata are on dopamine dendrites and 6% are on a type of unlabelled dendrite characterized by its peculiarly high cytoplasmic content of microtubules. The comparison of the diameter of the dendritic profiles that were in synaptic contact with serotonin-immunoreactive varicosities with the diameter of all other dendritic profiles of the same type suggests that serotoninergic varicosities innervate dopamine dendrites uniformly along their length, whereas they tend to contact microtubule-filled dendrites in more proximal regions and the other, unidentified dendrites in more distal regions. Furthermore, the size of the serotonin-immunoreactive varicosities and of their synaptic junctions is significantly smaller on dopamine dendrites and larger on microtubule-filled dendrites than on other, unidentified dendrites, indicating that the nature of the postsynaptic target is an important determinant of synaptic dimensions. These data should help to clarify the role of serotonin in the nigral control of motor functions. They indicate that this dense serotonin input to the substantia nigra is very precisely organized, acting through both "non-junctional" and "junctional" modes of neurotransmission in the pars compacta, which projects to the neostriatum and the limbic system, whereas the predominant mode of serotonin transmission appears to be of the "junctional" type in the pars reticulata, where serotonin can finely control the motor output of the basal ganglia by acting on the GABA projection neurons either directly or through the local release of dopamine by dopaminergic dendrites. The data also raise the possibility that the postsynaptic targets have trophic retrograde influences on serotoninergic terminals.

Animals↗

PubMed1995

CNS distribution and overexpression of neurofilament light proteins (NF-L) in mice transgenic for the human NF-L: aberrant accumulation in thalamic perikarya.

Light microscopic immunocytochemistry with monoclonal antibodies recognizing both murine and human light neurofilament proteins (mNF-L and hNF-L) or hNF-L only was used to examine the distribution of NF-L in the CNS of adult mice, normal or transgenic for the human gene. In normal mice, major fiber bundles were immunoreactive to the first antibody, with few exceptions such as the internal capsule, anterior commissure, and corpus callosum. Strong immunoreactivity was also present in the perikarya of motoneurons in the spinal cord and brainstem, as well as in other brainstem nuclei. Faint cell body staining was visible in layers II, III, and V of the parietal cortex and layers V and VI of the retrosplenial cingulate cortex. In transgenic mice, all forebrain as well as brainstem fiber tracts were intensely immunoreactive to both antibodies. Cell body staining was more intense than in normal mouse and involved additional forebrain and brainstem regions, including extended areas of cerebral cortex. Abnormal cell body labeling was particularly striking in several thalamic nuclei, where numerous darkly stained perikarya were considerably enlarged by accumulated immunoreactive material and exhibited eccentric and fragmented nuclei. At the electron microscopic level, these perikarya were filled with disarrayed filaments displacing all other organelles against the cytoplasmic membrane. Such aberrant accumulation of NF-L was presumably the result of an overexpression in selective subpopulations of CNS neurons. It was compatible with prolonged survival of the animal and could provide a new experimental model of neurodegenerative disease.

Animals↗

PubMed1994

Host serotonin axons innervate intrastriatal ventral mesencephalic grafts after implantation in newborn rats.

This study investigated the potential of immature and adult serotonin (5-HT) neurons for axonal growth into intrastriatal grafts of ventral mesencephalic tissue. Implantation of dissociated fetal (embryonic days 14-15) ventral mesencephalic tissue was carried out in immature [postnatal days (P) 5-14] and adult rat neostriatum. The brains were processed 2-6 months later for dopamine and 5-HT immunocytochemistry. A few grafts implanted into adult and P7 recipients contained small numbers of cotransplanted 5-HT cell bodies. These also displayed a rich network of 5-HT axons, even in adult rats prelesioned with 5,7-dihydroxytryptamine, indicating the graft origin of these axons. All other grafts were totally devoid of 5-HT cell bodies. After implantation in adults, such grafts contained rare 5-HT axons. In contrast, in P5-P7 recipients, they displayed many 5-HT fibres, which were uniformly distributed. Such was no longer the case after implantation in P14 recipients, which showed minimal 5-HT innervation, as in adult recipients. Processing of naïve rat brain at different ages for 5-HT immunocytochemistry showed that 5-HT axons were still clearly less numerous in the neostriatum at P21 than in adults, whereas in the substantia nigra the 5-HT innervation developed more rapidly and was comparable, at P21, to that of adults. It was concluded that 5-HT axons are able to grow into ventral mesencephalic grafts, but mainly at the fetal stage and with decreasing capacity after birth.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1993

Host striatal projections into fetal ventral mesencephalic tissue grafted to the striatum of immature or adult rat.

We have previously reported that few striatal axons from adult host brain innervate intrastriatal grafts of fetal ventral mesencephalic tissue. To see whether the immature rat brain would favor striatal innervation of the graft, unilateral implantation of fetal ventral mesencephalic tissue was carried out at 7 (P7), 14 (P14), or 60 (adults) days of age in neonatally dopamine-(DA)-lesioned and nonlesioned rats. Immunocytochemistry for tyrosine hydroxylase (TH), and/or dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein-32 (DARPP-32) was performed 2-6 months later. In the great majority of immature and in all adult recipients, the resulting graft consisted of a distinct intrastriatal mass of tissue surrounded by the host parenchyma. Most TH-immunopositive neurons were found within the confines of such grafts, although some were lying at short distances into the host striatal tissue, particularly in immature recipients. In a few immature recipients, there was, however, extensive intermingling of TH-positive neurons with the adjacent host brain tissue. In all recipients grafted at P7, P14, or as adults, the distinct, intraparenchymal grafts contained moderate numbers of DARPP-32-positive processes, mainly at their periphery. These results indicate that the limited capacity of host striatal neurons to grow axons into transplanted fetal ventral mesencephalic tissue is not markedly different in young versus adult rats. A better integration of the ventral mesencephalic graft into the striatal circuitry of immature--as opposed to adult--recipients should therefore rely more on the higher tendency of DA neurons to become located into the host tissue following transplantation in young rats.

Animals↗

PubMed1971