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Apomorphine induces trophic factors that support fetal rat mesencephalic dopaminergic neurons in cultures
Author(s) -
Guo Hong,
Tang Zhongshu,
Yu Yi,
Xu Lei,
Jin Guozhang,
Zhou Jiawei
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02256.x
Subject(s) - apomorphine , dopaminergic , endocrinology , neurotrophic factors , medicine , dopamine , glial cell line derived neurotrophic factor , nerve growth factor , tyrosine hydroxylase , brain derived neurotrophic factor , neurotrophin , dopamine receptor , biology , chemistry , receptor
Apomorphine, the catechol‐derived dopamine D 1 /D 2 receptor agonist, is currently in use as an antiparkinsonian drug. It has previously been reported that apomorphine was able to elicit expression of the enzyme tyrosine hydroxylase, a marker for DA neurons, in the fetal rat cerebrocortical cultures whilst in the presence of brain‐derived neurotrophic factor. The present study demonstrated that treatment of fetal rat ventral mesencephalic cultures with apomorphine caused a marked increase in the number of dopaminergic neurons. The action of apomorphine can be mimicked by dopamine receptor (D 1 and D 2 ) agonists or blocked by preincubation with D 1 /D 2 receptor antagonists. Incubation of recipient mesencephalic cultures with the conditioned medium derived from apomorphine‐stimulated donor mesencephalic cultures elicited a 3.72‐fold increase in the number of TH‐positive neurons. Increased mRNA expression levels of brain‐derived neurotrophic factor and glial cell line‐derived neurotrophic factor were also found in the apomorphine‐treated mesencephalic cells along with concomitant protein expression increases in the conditioned medium. Moreover, the trophic activity observed could be partially neutralized by antibodies against either brain‐derived neurotrophic factor or glial cell line‐derived neurotrophic factor. Cultured fetal striatal cells, but not hippocampal cells, also responded to apomorphine treatment. The membrane filtration studies revealed that both <30 kDa and >50 kDa fractions contained trophic activities. The latter characterization distinguishes them from most known neurotrophic factors. These results suggest that the apomorphine‐modulated development of dopaminergic neurons may be mediated by activation of the dopamine receptor subtypes D 1 and D 2 thereby increasing the production of multiple growth factors.