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Neurogenesis of dopaminergic neurons in the adult mammalian olfactory bulb: a possible source of cells for neural repair strategies
No full textContrary to previously held beliefs, the adult brain is in fact capable of generating new neurons that
can integrate into its complex circuitry. Recent researches have demonstrated that neurogenesis
constitutively occurs in two specific regions of the adult mammalian brain, olfactory bulb (OB) and
hippocampus. In the OB there is a significant number of dopaminergic (DA) precursors, originated
from the subventricular zone and migrated following the rostral migratory stream. The properties of
these cells have been studied with the patch-clamp technique in a transgenic animal model
expressing GFP under the tyrosine hydroxylase (TH) promoter. Using BrdU we have first
demonstrated that, in regions not normally occupied by DA neurones (mitral and extemal plexiform
layers, ML and EPL) there are cells in which the transcription of the TH gene occurs in the absence
of significant translational activity. We have studied the functional properties of these cells,
showing that they seem to reflect different degree of maturation towards the DA phenotype as they
become progressively closer to their final destination, the glomerular layer. In fact, cells in the EPL
are autorhythmic, as are mature DA neurons in the glomerular layer, whereas TH-GFP cells in the
ML are not. Furthermore, the cells in the EPL are synaptically connected to the olfactory nerve,
whereas those in the ML are not. A new technique, based on dielectrophoresis, is being developed
to sort immature DA neurones. It is hoped that these cells, present in a region easily accessible with
surgical techniques, expanded in vitro and induced to differentiate towards the DA phenotype,
could be a convenient source of neurons for cellular replacement strategies to treat
neurodegenerative diseases affecting DA systems
Neurogenesis of dopaminergic neurons in the adult mammalian olfactory bulb: a possible source of cells for neural repair strategies
No full textContrary to previously held beliefs, the adult brain is in fact capable of generating new neurons that
can integrate into its complex circuitry. Recent researches have demonstrated that neurogenesis
constitutively occurs in two specific regions of the adult mammalian brain, olfactory bulb (OB) and
hippocampus. In the OB there is a significant number of dopaminergic (DA) precursors, originated
from the subventricular zone and migrated following the rostral migratory stream. The properties of
these cells have been studied with the patch-clamp technique in a transgenic animal model
expressing GFP under the tyrosine hydroxylase (TH) promoter. Using BrdU we have first
demonstrated that, in regions not normally occupied by DA neurones (mitral and extemal plexiform
layers, ML and EPL) there are cells in which the transcription of the TH gene occurs in the absence
of significant translational activity. We have studied the functional properties of these cells,
showing that they seem to reflect different degree of maturation towards the DA phenotype as they
become progressively closer to their final destination, the glomerular layer. In fact, cells in the EPL
are autorhythmic, as are mature DA neurons in the glomerular layer, whereas TH-GFP cells in the
ML are not. Furthermore, the cells in the EPL are synaptically connected to the olfactory nerve,
whereas those in the ML are not. A new technique, based on dielectrophoresis, is being developed
to sort immature DA neurones. It is hoped that these cells, present in a region easily accessible with
surgical techniques, expanded in vitro and induced to differentiate towards the DA phenotype,
could be a convenient source of neurons for cellular replacement strategies to treat
neurodegenerative diseases affecting DA systems
Neurogenesis of Dopaminergic Neurons in the Adult Mammalian Olfactory Bulb: A Possible Source of Cells for Neural Repair Strategies
No full textContrary to previously held beliefs, the adult brain is in fact capable of generating new neurons that can integrate into its complex circuitry. Recent researches have demonstrated that neurogenesis constitutively occurs in two specific regions of the adult mammalian brain, olfactory bulb (OB) and hippocampus. In the OBthere is a significant number of dopaminergic (DA) precursors, originated from the subventricular zone and migrated following the rostral migratory stream. The properties of these cells has been studied with the patch-clamp technique in a transgenic animalmodel expressing GFP under the tyrosine hydroxylase (TH) promoter. Using BrdU we have first demonstrated that, in regions not normally occupied by DA neurones (mitral and external plexiform layers, ML and EPL) there are cells in which the transcription of the TH gene occurs in the absence of significant translational activity. We have studied the functional properties of these cells, showing that they seem to reflect different degree of maturation towards the DA phenotype as they become progressively closer to their final destination, the glomerular layer. In fact, cells in the EPL are autorhythmic, as are mature DA neurons in the glomerular layer, whereas TH-GFP cells in the ML are not. Furthermore, the cells in the EPL are synaptically connected to the olfactory nerve, whereas those in the ML are not. A new technique, based on dielectrophoresis, is being developed to sort immature DA neurones. It is hoped that these cells, present in a region easily accessible with surgical techniques, expanded in vitro and induced to differentiate towards the DA phenotype, could be a convenient source of neurons for cellular replacement strategies to treat neurodegenerative diseases affecting DA systems
Functional properties of immature dopaminergic neurons in the adult mammalian olfactory bulb
No full textAbstract non disponibil
Expression and role of complex carbohydrates in axon guidance in the olfactory system
No full textPrimary sensory neurons in the vertebrate olfactory systems are characterised by the differential expression of distinct cell surface carbohydrates. We show here that the histo-blood groups Sda (or CT1 antigen) and H are expressed by primary sensory neurons in the olfactory system, while the blood group A carbohydrate is expressed by a subset of vomeronasal neurons only in the developing accessory olfactory system. We have used both loss-of-function and gain-of-function approaches to manipulate expression of these carbohydrates in the olfactory system. In null mutant mice lacking the alpha(1,2)fucosyltransferase FUT1, the blood group H and A carbohydrates were not expressed in the olfactory systems which caused delayed development of the nerve fibre and glomerular layers in the main olfactory bulb. In contrast, ubiquitous expression of blood group A on olfactory axons in gain-of-function transgenic mice perturbed the ability of vomeronasal axons to terminate in the accessory olfactory bulb and affected the selective targeting of axons in the main olfactory bulb. During regeneration following bulbectomy, vomeronasal axons were unable to effectively sort out from the main olfactory axons when blood group A was misexpressed. These results provide in vivo evidence for a role of specific cell surface carbohydrates during development and regeneration of the olfactory nerve pathways
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