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Expression of acidic and basic fibroblast growth factors in the substantia nigra of rat, monkey, and human
1Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Abstract:
The distribution of acidic (aFGF) and basic (bFGF) fibroblast growth factor mRNA and protein were examined in mesencephalon by immunohistochemistry, immunoblot analysis, in situ hybridization histochemistry, and RNA analysis. Coexistence of aFGF or bFGF with tyrosine hydroxylase protein in nigral cells was observed with immunohistochemistry. Both aFGF and bFGF mRNAs were found in the substantia nigra. Unilateral 6-hydroxydopamine lesions of nigrostriatal neurons resulted in a loss of aFGF and tyrosine hydroxylase [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] mRNA-positive neurons on the lesioned side. The distribution of aFGF mRNA in monkey brain was similar to that seen in the rat. RNA and immunoblot analysis confirmed the presence of both aFGF and bFGF mRNAs and proteins in the substantia nigra of rat, monkey, and human.
Insights
Acidic and basic fibroblast growth factor (aFGF and bFGF) are present in the substantia nigra. Lesions causing neuron loss also reduced aFGF mRNA, suggesting its role in nigrostriatal neuron survival.
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- Acidic (aFGF) and basic (bFGF) fibroblast growth factors are implicated in neuronal development and survival.
- Their specific roles and distribution within the mesencephalon, particularly the substantia nigra, require further elucidation.
Purpose of the Study:
- To investigate the distribution and localization of aFGF and bFGF mRNA and protein in the mesencephalon.
- To determine the relationship between aFGF/bFGF and dopaminergic neurons in the substantia nigra.
- To assess the impact of nigrostriatal pathway damage on aFGF and tyrosine hydroxylase mRNA levels.
Main Methods:
- Immunohistochemistry to detect protein co-localization.
- Immunoblot analysis for protein quantification.
- In situ hybridization histochemistry and RNA analysis for mRNA distribution.
Main Results:
- Both aFGF and bFGF were found in the substantia nigra, co-existing with tyrosine hydroxylase protein in nigral cells.
- aFGF and bFGF mRNAs were detected in the substantia nigra.
- Unilateral 6-hydroxydopamine lesions led to a decrease in aFGF and tyrosine hydroxylase mRNA-positive neurons on the lesioned side.
- aFGF mRNA distribution in monkey brain mirrored that in rats.
- aFGF and bFGF mRNAs and proteins were confirmed in the substantia nigra of rats, monkeys, and humans.
Conclusions:
- aFGF and bFGF are expressed in the substantia nigra across species (rat, monkey, human).
- The presence of aFGF mRNA in tyrosine hydroxylase-positive neurons suggests a potential role in dopaminergic neuron function.
- The reduction of aFGF mRNA following neuronal lesioning indicates a possible involvement in nigrostriatal neuron survival.