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Differential ultrastructural alterations in the Vglut2 glutamatergic input to the substantia nigra pars compacta/pars reticulata following nigrostriatal dopamine loss in a progressive mouse model of Parkinson's disease.
Eur J Neurosci. 2020 Jul 03 [Online ahead of print]EJ

Abstract

Loss of nigrostriatal dopamine (DA) in Parkinson's disease results in over-activation/bursting of the subthalamic nucleus (STN). The STN projects to the substantia nigra (SN) pars compacta (SNpc) and pars reticulata (SNpr). The vesicular glutamate transporter 2 (Vglut2) is localized within at least STN terminals synapsing within the SN, but it is not known if there are differential changes in the Vglut2+ input to the SNpc versus SNpr following DA loss. The goal/rationale of this current study was to determine whether there were differential changes in the density/levels of glutamate immuno-gold labeling within Vglut2+ nerve terminals synapsing in the SNpc/SNpr and in the proportion of Vglut2+ terminals contacting tyrosine hydroxylase (TH) positively(+) or negatively(-) labeled dendrites following DA loss. Within the SNpc, there was a significant increase (51.3%) in the density of nerve terminal glutamate immuno-gold labeling within Vglut2+ terminals synapsing on TH(-) dendrites following MPTP versus the vehicle (VEH) group. There was a significant decrease (16%) in the percentage of Vglut2+ terminals contacting TH(+) labeled dendrites in the MPTP- versus VEH-treated group within the SNpc. Within the SNpr, there was a significant decrease in the density of glutamate immuno-gold labeling in Vglut2+ terminals contacting TH(+) (71.5%) and TH(-) (55.5%) labeled dendrites, suggesting an increase in glutamate release. There was no change in the percentage of Vglut2+ terminals contacting TH(+) or TH(-) dendrites in the SNpr. We conclude that there is a differential effect following DA loss on the glutamate input from Vglut2+ terminals synapsing within the SNpr versus SNpc.

Authors+Show Affiliations

Research Services, VA Medical Center/Portland, Portland, OR, USA.Research Services, VA Medical Center/Portland, Portland, OR, USA.Research Services, VA Medical Center/Portland, Portland, OR, USA.Research Services, VA Medical Center/Portland, Portland, OR, USA. Department of Behavioral Neuroscience and Pathology, Oregon Heath & Science University, Portland, OR, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32619030

Citation

Moore, Cynthia, et al. "Differential Ultrastructural Alterations in the Vglut2 Glutamatergic Input to the Substantia Nigra Pars Compacta/pars Reticulata Following Nigrostriatal Dopamine Loss in a Progressive Mouse Model of Parkinson's Disease." The European Journal of Neuroscience, 2020.
Moore C, Xu M, Bohlen JK, et al. Differential ultrastructural alterations in the Vglut2 glutamatergic input to the substantia nigra pars compacta/pars reticulata following nigrostriatal dopamine loss in a progressive mouse model of Parkinson's disease. Eur J Neurosci. 2020.
Moore, C., Xu, M., Bohlen, J. K., & Meshul, C. K. (2020). Differential ultrastructural alterations in the Vglut2 glutamatergic input to the substantia nigra pars compacta/pars reticulata following nigrostriatal dopamine loss in a progressive mouse model of Parkinson's disease. The European Journal of Neuroscience. https://doi.org/10.1111/ejn.14894
Moore C, et al. Differential Ultrastructural Alterations in the Vglut2 Glutamatergic Input to the Substantia Nigra Pars Compacta/pars Reticulata Following Nigrostriatal Dopamine Loss in a Progressive Mouse Model of Parkinson's Disease. Eur J Neurosci. 2020 Jul 3; PubMed PMID: 32619030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential ultrastructural alterations in the Vglut2 glutamatergic input to the substantia nigra pars compacta/pars reticulata following nigrostriatal dopamine loss in a progressive mouse model of Parkinson's disease. AU - Moore,Cynthia, AU - Xu,Mo, AU - Bohlen,Jerry K, AU - Meshul,Charles K, Y1 - 2020/07/03/ PY - 2020/01/30/received PY - 2020/06/26/revised PY - 2020/06/27/accepted PY - 2020/7/4/pubmed PY - 2020/7/4/medline PY - 2020/7/4/entrez KW - MPTP KW - electron microscopy KW - immunohistochemistry KW - subthalamic nucleus KW - vesicular glutamate transporter 2 JF - The European journal of neuroscience JO - Eur. J. Neurosci. N2 - Loss of nigrostriatal dopamine (DA) in Parkinson's disease results in over-activation/bursting of the subthalamic nucleus (STN). The STN projects to the substantia nigra (SN) pars compacta (SNpc) and pars reticulata (SNpr). The vesicular glutamate transporter 2 (Vglut2) is localized within at least STN terminals synapsing within the SN, but it is not known if there are differential changes in the Vglut2+ input to the SNpc versus SNpr following DA loss. The goal/rationale of this current study was to determine whether there were differential changes in the density/levels of glutamate immuno-gold labeling within Vglut2+ nerve terminals synapsing in the SNpc/SNpr and in the proportion of Vglut2+ terminals contacting tyrosine hydroxylase (TH) positively(+) or negatively(-) labeled dendrites following DA loss. Within the SNpc, there was a significant increase (51.3%) in the density of nerve terminal glutamate immuno-gold labeling within Vglut2+ terminals synapsing on TH(-) dendrites following MPTP versus the vehicle (VEH) group. There was a significant decrease (16%) in the percentage of Vglut2+ terminals contacting TH(+) labeled dendrites in the MPTP- versus VEH-treated group within the SNpc. Within the SNpr, there was a significant decrease in the density of glutamate immuno-gold labeling in Vglut2+ terminals contacting TH(+) (71.5%) and TH(-) (55.5%) labeled dendrites, suggesting an increase in glutamate release. There was no change in the percentage of Vglut2+ terminals contacting TH(+) or TH(-) dendrites in the SNpr. We conclude that there is a differential effect following DA loss on the glutamate input from Vglut2+ terminals synapsing within the SNpr versus SNpc. SN - 1460-9568 UR - https://www.unboundmedicine.com/medline/citation/32619030/Differential_ultrastructural_alterations_in_the_Vglut2_glutamatergic_input_to_the_substantia_nigra_pars_compacta/pars_reticulata_following_nigrostriatal_dopamine_loss_in_a_progressive_mouse_model_of_Parkinson's_disease L2 - https://doi.org/10.1111/ejn.14894 DB - PRIME DP - Unbound Medicine ER -
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