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The high molecular weight fibroblast growth factor-2 isoforms (21,000 mol. wt and 23,000 mol. wt) mediate neurotrophic activity on rat embryonic mesencephalic dopaminergic neurons in vitro.

Abstract：

:Basic fibroblast growth factor is expressed in different isoforms which display tissue and species specificity and are differentially regulated during development and after experimental interventions. The differential regulation of the fibroblast growth factor-2 isoforms may indicate specific activities and functions of these molecules. The characterization of fibroblast growth factor-2 effects, however, is almost exclusively based on studies including the 18,000 mol. wt isoform. It is not yet known whether the high molecular weight fibroblast growth factor-2 isoforms (21,000 mol. wt, 23,000 mol. wt) exert similar or distinct activities in the nervous system. In the present study, we investigated the effects of the high molecular weight isoforms on dissociated rat mesencephalic dopaminergic neurons. For this purpose, recombinant fibroblast growth factor-2 isoforms, prepared in a histidine expression system, were administered on dopaminergic neurons in vitro, and Schwann cells over-expressing the high molecular weight isoforms were co-cultured with dopaminergic neurons. This is the first demonstration to show that the high molecular weight isoforms mediate a neurotrophic activity. Exogenous high molecular weight fibroblast growth factor-2 isoforms stimulated the survival of embryonic mesencephalic dopaminergic neurons and protected them from 6-hydroxydopamine neurotoxicity. In addition, co-culture of dopaminergic neurons with high molecular weight fibroblast growth factor-2 over-expressing Schwann cells revealed an increased survival and neurite formation of the mesencephalic dopaminergic neurons. These results suggest that the high molecular weight fibroblast growth factor-2 isoforms may serve as a new tool for the treatment of Parkinson's disease.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Grothe C,Schulze A,Semkova I,Müller-Ostermeyer F,Rege A,Wewetzer K

doi

10.1016/s0306-4522(00)00247-5

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

73-86

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(00)00247-5

journal_volume

100

pub_type

杂志文章

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The high molecular weight fibroblast growth factor-2 isoforms (21,000 mol. wt and 23,000 mol. wt) mediate neurotrophic activity on rat embryonic mesencephalic dopaminergic neurons in vitro.