Repository logo
 

Factors influencing the survival, growth and development of central nervous system neurons in the fetal rat and human.

Date

1996

Authors

Chalmers-Redman, Ruth Mary Elizabeth.

Journal Title

Journal ISSN

Volume Title

Publisher

Dalhousie University

Abstract

Description

This thesis examines factors affecting the in vivo and in vitro survival, growth and development of CNS neurons from both rat and human. Target cells exert profound effects on projection neurons, as revealed by loss of tyrosine hydroxylase immunoreactive neurons in the ipsilateral substantia nigra after ibotenic acid lesioning of the striatum, the main target of these neurons. Grafting of fetal striatal primordia to the lesioned striatum resulted in a slight decrease in this effect, suggesting that striatal cells provide a trophic influence on the dopaminergic SN neurons. Retrograde bead labelling studies indicate that six weeks post-lesion, an increased number of bead-labelled cells do not express tyrosine hydroxylase immunoreactivity; such cells may be impaired but living dopaminergic striatal-projecting SN neurons.
The trophic support provided by the striatum may be in the form of protein trophic factors. Among the specific growth factors I examined in vitro, brain derived neurotrophic factor and basic fibroblast growth factor with heparin enhanced the number of surviving human fetal ventral mesencephalic dopaminergic neurons.
The dopaminergic precursor, L-dopa, has been suggested to have toxic effects on dopaminergic neurons in vivo and in vitro. In the experiments described here, however, L-dopa at drug dosages comparable to human therapy for Parkinson's disease had no toxic effect on either human or rat dopaminergic cells in vitro, or on fetal rat ventral mesencephalic grafts in vivo.
Progenitor cells from the fetal human forebrain can propagate in a growth-factor supplemented medium, and can subsequently be induced to express a variety of glial and neuronal phenotypes including dopamine. These cells exhibit a less than 48 hour cycle time as indicated by bromodeoxyuridine incorporation. These cells could be useful for pharmacological studies, examination of growth factors, transfection of desired genes of transplantation.
Thesis (Ph.D.)--Dalhousie University (Canada), 1996.

Keywords

Biology, Anatomy., Biology, Neuroscience.

Citation