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Dopaminergic neurons in rat ventral midbrain express brain‐derived neurotrophic factor and neurotrophin‐3 mRNAs

Dopaminergic neurons in rat ventral midbrain express brain‐derived neurotrophic factor and... Studies of the trophic activities of brain‐derived neurotrophic factor and neurotrophin‐3 indicate that both molecules support the survival of a number of different embryonic cell types in culture. We have shown that mRNAs for brain‐derived neurotrophic factor and neurotrophin‐3 are localized to specific ventral mesencephalic regions containing dopaminergic cell bodies, including the substantia nigra and ventral tegmental area. In the present study, in situ hybridization with 35S‐labeled cRNA probes for the neurotrophin mRNAs was combined with neurotoxin lesions or with immunocytochemistry for the catecholamine‐synthesizing enzyme tyrosine hydroxylase to determine whether the dopaminergic neurons, themselves, synthesize the neurotrophins in adult rat midbrain. Following unilateral destruction of the midbrain dopamine cells with 6‐hydroxydopamine, a substantial, but incomplete, depletion of brain‐derived neurotrophic factor and neurotrophin‐3 mRNA‐containing cells was observed in the ipsilateral substantia nigra pars compacta and ventral tegmental area. In other rats, combined in situ hybridization and tyrosine hydroxylase immunocytochemistry demonstrated that the vast majority of the neurotrophin mRNA‐containing neurons in the substantia nigra and ventral tegmental area were tyrosine hydroxylase immunoreactive. Of the total population of tyrosine hydroxylase‐positive cells, double‐labeled neurons constituted 25–50% in the ventral tegmental area and 10–30% in the substantia nigra pars compacta, with the proportion being greater in medial pars compacta. In addition, tyrosine hydroxylase/neurotrophin mRNA coexistence was observed in neurons in other mesencephalic regions including the retrorubral field, interfascicular nucleus, rostral and central linear nuclei, dorsal raphe nucleus, and supramammillary region. The present results demonstrate brain‐derived neurotrophic factor and neurotrophin‐3 expression by adult midbrain dopamine neurons and support the suggestion that these neurotrophins influence dopamine neurons via autocrine or paracrine mechanisms. These data raise the additional possibility that inappropriate expression of the neurotrophins by dopaminergic neurons could contribute to the neuropathology of disease states such as Parkinson's disease and schizophrenia. © 1994 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Comparative Neurology Wiley

Dopaminergic neurons in rat ventral midbrain express brain‐derived neurotrophic factor and neurotrophin‐3 mRNAs

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References (83)

Publisher
Wiley
Copyright
"Copyright © 1994 Wiley Subscription Services, Inc., A Wiley Company"
ISSN
0021-9967
eISSN
1096-9861
DOI
10.1002/cne.903420302
pmid
7912699
Publisher site
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Abstract

Studies of the trophic activities of brain‐derived neurotrophic factor and neurotrophin‐3 indicate that both molecules support the survival of a number of different embryonic cell types in culture. We have shown that mRNAs for brain‐derived neurotrophic factor and neurotrophin‐3 are localized to specific ventral mesencephalic regions containing dopaminergic cell bodies, including the substantia nigra and ventral tegmental area. In the present study, in situ hybridization with 35S‐labeled cRNA probes for the neurotrophin mRNAs was combined with neurotoxin lesions or with immunocytochemistry for the catecholamine‐synthesizing enzyme tyrosine hydroxylase to determine whether the dopaminergic neurons, themselves, synthesize the neurotrophins in adult rat midbrain. Following unilateral destruction of the midbrain dopamine cells with 6‐hydroxydopamine, a substantial, but incomplete, depletion of brain‐derived neurotrophic factor and neurotrophin‐3 mRNA‐containing cells was observed in the ipsilateral substantia nigra pars compacta and ventral tegmental area. In other rats, combined in situ hybridization and tyrosine hydroxylase immunocytochemistry demonstrated that the vast majority of the neurotrophin mRNA‐containing neurons in the substantia nigra and ventral tegmental area were tyrosine hydroxylase immunoreactive. Of the total population of tyrosine hydroxylase‐positive cells, double‐labeled neurons constituted 25–50% in the ventral tegmental area and 10–30% in the substantia nigra pars compacta, with the proportion being greater in medial pars compacta. In addition, tyrosine hydroxylase/neurotrophin mRNA coexistence was observed in neurons in other mesencephalic regions including the retrorubral field, interfascicular nucleus, rostral and central linear nuclei, dorsal raphe nucleus, and supramammillary region. The present results demonstrate brain‐derived neurotrophic factor and neurotrophin‐3 expression by adult midbrain dopamine neurons and support the suggestion that these neurotrophins influence dopamine neurons via autocrine or paracrine mechanisms. These data raise the additional possibility that inappropriate expression of the neurotrophins by dopaminergic neurons could contribute to the neuropathology of disease states such as Parkinson's disease and schizophrenia. © 1994 Wiley‐Liss, Inc.

Journal

The Journal of Comparative Neurology – Wiley

Published: Mar 15, 1995

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