English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Development of mesencephalic dopaminergic cells is well characterized in rodents and partially defined in primates. In the human fetus, tyrosine hydroxylase (TH) immunoreactivity was first observed at 7 weeks of gestation. Migration and neuritic elongation of TH+ cells were monitored from 7 to 12 weeks of gestational age. Intact fetal mesencephalon was post-fixed and sections obtained to demonstrate dopaminergic cell anatomical location. At 8 weeks, TH+ neurons were found in a crescentic band occupying the middle third of the ventral mesencephalon. TH cell migration was confirmed in the medial third of the ventral mesencephalon at 9 weeks and by 11 weeks a large number of dopaminergic cells had elaborated neural processes. These data complement the observations of Freeman et aL/3/that similarly described early dopaminergic cellular development. Growth potentialities of the dopaminergic cells were evaluated in primary cultures. Neuronal cells were identified for non-specific markers (Neuron Specific Enolase). TH cells represented 1 to 2.5% of the total neuronal population, strictly dependent on precise dissection. One peculiar feature of TH+ neurons is the formation of long neurite (axons) projections in the presence and absence of the co-cultured striatal-specific target. Treatment of these cultures with fibroblast growth factors (FGF) significantly increased the number of surviving TH+ neurons at 8 d in vitro and induced proliferation of glial cells. Dopaminergic cells showed specific tropism for astroglial GFAP+ cells. Previous studies demonstrated that mesencephalic glia specifically support the survival of dopaminergic neurons and induce dendritic outgrowth /2,4/. Some of the GFAP+ cells were shown to express NGF-low affinity receptors (NGF-R) on the membrane surface. NGF-R were identified with double staining for GFAP and NGF-R, using a confocal microscopy technique (monoclonal antibody against NGF-R obtained from clone ME 20-4 and 8211). TH, the rate-limiting enzyme in the biosynthesis of catecholamines, was biochemically assayed as a quantitative index of dopaminergic cell number and viability. Enzymatic activity was determined using the TH microassay described by Bostwick et al. /1/. This microradiometric assay can detect the production of 5 pmol of xaco.(coupled non-enzymatic decarboxylation of Dopa). 105 cells were plated in a 96 microwell plate and the TH activity assayed at days 6 to 10. Linearity of the TH enzyme reaction with time and protein concentration was demonstrated. TH activity was shown to increase by culture day 6 and then to decline. Characterization of developmental events in the human mesencephalic dopaminergic neurons provides significant pre-clinical information to define the optimal age characteristics for brain grafting. Percentage of dopaminergic neurons and number of proliferating glial cells may be controlled after precise anatomical dissection. A TH microassay was applied to the human dopaminergic cells in vitro and FGF was shown to affect TH+ neuronal cell development. Further investigations on glial-mediated processes in the human nigra are necessary to define the direct/indirect effects of FGF on dopaminergic neurons.

In vivo and in vitro Development of Human Mesencephalic Dopaminergic Neurons