Neuroscience 2005 Abstract
| Presentation Number: | 155.6 |
|---|---|
| Abstract Title: | A 6-OHDA lesion upregulates VGLUT2 expression in dopaminergic neurons of the VTA. |
| Authors: |
Dal Bo, G.*1,2
; Levesque, D.3
; Trudeau, L.1,2
1Pharmacology, Univ. of Montreal, Montreal, Canada 2CRSN, Univ. of Montreal, Montreal, Canada 3PQ, CP 6128 succursale centreville, H3C 3J7, |
| Primary Theme and Topics |
Neural Excitability, Synapses, and Glia: Cellular Mechanisms - Transporters -- Vesicular |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Neurodegenerative and Movement Disorders<br />-- Parkinson's disease: Cells, circuits, and systems |
| Session: |
155. Vesicular and Plasma Membrane Transporters Poster |
| Presentation Time: | Sunday, November 13, 2005 9:00 AM-10:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # F29 |
| Keywords: | dopamine, vesicular glutamate transporter, parkinson, 6-hydroxydopamine |
Dopaminergic (DAergic) neurons of substantia nigra (SN) and ventral tegmental area (VTA) release dopamine on their target neurons in striatum and nucleus accumbens respectively. Recent studies demonstrated that DAergic neurons in culture are able to release glutamate at synapses. We showed that close to 80% of isolated DAergic neurons in culture express the vesicular glutamate transporter 2 (VGluT2). However, only a small sub-population of DAergic neurons in the rostral linear nucleus expresses VGluT2 in vivo (Kawano et al., SFN 2004, 505.4). We hypothesize that VGLUT2 expression in DAergic neurons may be induced under pathological conditions.
To study VGluT2 regulation in DAergic neurons in vivo we used double in situ hybridization to localize VGluT2 and tyrosine hydroxylase (TH) mRNA. We examined VGluT2 expression in DAergic neurons during embryonic and postnatal (PN) development. At embryonic days 14 and 15, VGluT2 and TH labelling displayed significant overlap. In PN mesencephalon a quantitative analysis revealed that approximately 1-3% of neurons expressing TH mRNA also expressed VGluT2 mRNA in the VTA and SN of control rats. To explore the regulation of VGLUT2 expression in DAergic neurons in pathological models, we used the 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. At PN 4, rats received a desipramine injection to protect noradrenergic neurons and then a 6-OHDA injection in each lateral ventricle. Animals were examined at different times post-surgery. In 6-OHDA animals, we found that close to 30% of surviving DAergic neurons in the VTA and 5% in the SN expressed VGluT2 mRNA. In shams animals and in rats treated with desipramine alone, 15% of TH+ neurons in the VTA expressed VGluT2 mRNA and 2-5% in the SN. Our results suggest that the glutamatergic phenotype of DAergic neurons is developmentally regulated, and can be reactivated under pathological states. The functional implications of such plasticity in the neurotransmitter repertoire of DAergic neurons remain to be determined.
To study VGluT2 regulation in DAergic neurons in vivo we used double in situ hybridization to localize VGluT2 and tyrosine hydroxylase (TH) mRNA. We examined VGluT2 expression in DAergic neurons during embryonic and postnatal (PN) development. At embryonic days 14 and 15, VGluT2 and TH labelling displayed significant overlap. In PN mesencephalon a quantitative analysis revealed that approximately 1-3% of neurons expressing TH mRNA also expressed VGluT2 mRNA in the VTA and SN of control rats. To explore the regulation of VGLUT2 expression in DAergic neurons in pathological models, we used the 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. At PN 4, rats received a desipramine injection to protect noradrenergic neurons and then a 6-OHDA injection in each lateral ventricle. Animals were examined at different times post-surgery. In 6-OHDA animals, we found that close to 30% of surviving DAergic neurons in the VTA and 5% in the SN expressed VGluT2 mRNA. In shams animals and in rats treated with desipramine alone, 15% of TH+ neurons in the VTA expressed VGluT2 mRNA and 2-5% in the SN. Our results suggest that the glutamatergic phenotype of DAergic neurons is developmentally regulated, and can be reactivated under pathological states. The functional implications of such plasticity in the neurotransmitter repertoire of DAergic neurons remain to be determined.
Supported by CIHR
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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