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Ultrastructural Analysis of Nigrostriatal Dopaminergic Terminals in a Knockin Mouse Model of DYT1 Dystonia
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  • Ke Pan,
  • Hyder Jinnah,
  • Ellen Hess,
  • Yoland Smith,
  • Rosa Villalba
Ke Pan
Emory University
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Hyder Jinnah
Emory University
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Ellen Hess
Emory University
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Yoland Smith
Emory University
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Rosa Villalba
Emory University

Corresponding Author:[email protected]

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DYT1 dystonia is a form of generalized dystonia associated with abnormalities in striatal dopamine release in mouse models and likely in humans. In the present study, we examined the possibility that ultrastructural changes in the morphology of nigrostriatal dopamine terminals could contribute to this neurochemical imbalance using a Serial-Block Face/Scanning Electron Microscope (SBF/SEM) and three-dimensional reconstruction approach to analyze striatal tyrosine hydroxylase-immunoreactive (TH-IR) terminals and their synapses in a DYT1(ΔE) Knockin (DYT1-KI) mouse model of DYT1 dystonia. Furthermore, to study possible changes in vesicle packaging capacity of dopamine, we used transmission electron microscopy to assess possible changes in the size of synaptic vesicles in striatal dopamine terminals between wild type (WT) and the DYT1-KI mice. Quantitative analysis of 80 fully reconstructed TH-IR terminals in the WT and DYT1-KI mice indicate: 1) No significant difference in the volume of TH-IR terminals between WT and DYT1-KI mice, 2) No major change in the proportion of axo-spinous vs axo-dendritic synapses formed by TH-IR terminals between the two groups, 3) No significant change in the post-synaptic density (PSD) area of axo-dendritic synapses, while the PSDs of axo-spinous synapses were significantly smaller in DYT1-KI mice, 4) No significant difference in the mean volume of mitochondria between WT mice and 5) No significant difference in the surface area of synaptic vesicles between the two groups. Altogether, these findings suggest that abnormal morphometric changes of nigrostriatal dopamine terminals and their post-synaptic targets are unlikely to be a major source of reduced striatal dopamine release in DYT1 dystonia.
08 Mar 2023Submitted to European Journal of Neuroscience
10 Mar 2023Submission Checks Completed
10 Mar 2023Assigned to Editor
10 Mar 2023Review(s) Completed, Editorial Evaluation Pending
16 Mar 2023Reviewer(s) Assigned
07 May 2023Editorial Decision: Revise Major
01 Sep 20231st Revision Received
02 Sep 2023Assigned to Editor
02 Sep 2023Review(s) Completed, Editorial Evaluation Pending
02 Sep 2023Submission Checks Completed
02 Sep 2023Reviewer(s) Assigned
04 Oct 2023Editorial Decision: Revise Major
02 Nov 20232nd Revision Received
03 Nov 2023Submission Checks Completed
03 Nov 2023Assigned to Editor
03 Nov 2023Review(s) Completed, Editorial Evaluation Pending
03 Nov 2023Reviewer(s) Assigned
05 Nov 2023Editorial Decision: Accept