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Research ArticleResearch Article: Negative Results, Disorders of the Nervous System

Mice Expressing A53T/A30P Mutant Alpha-Synuclein in Dopamine Neurons Do Not Display Behavioral Deficits

Cameron Keomanivong, Josephine Schamp, Ervina Tabakovic, Ramasamy Thangavel, Georgina Aldridge, Andrew A. Pieper and Nandakumar S. Narayanan
eNeuro 13 February 2024, 11 (2) ENEURO.0170-23.2023; https://doi.org/10.1523/ENEURO.0170-23.2023
Cameron Keomanivong
1Carver College of Medicine, University of Iowa, Iowa City 52245, Iowa
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Josephine Schamp
2York University, York 68467, Nebraska
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Ervina Tabakovic
1Carver College of Medicine, University of Iowa, Iowa City 52245, Iowa
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Ramasamy Thangavel
3Department of Neurology, University of Iowa, Iowa City 52245, Iowa
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Georgina Aldridge
3Department of Neurology, University of Iowa, Iowa City 52245, Iowa
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Andrew A. Pieper
4Brain Health Medicines Center, Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland 44106, Ohio; Department of Psychiatry, Case Western Reserve University, Cleveland 44106, Ohio; Geriatric Research Education and Clinical Center (GRECC), Louis Stokes Cleveland VA Medical Center, Cleveland 44106, Ohio; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland 44106, Ohio; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland 44106, Ohio; Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland 44106, Ohio; Translational Therapeutics Core, Cleveland Alzheimer’s Disease Research Center, Cleveland, Ohio
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Nandakumar S. Narayanan
3Department of Neurology, University of Iowa, Iowa City 52245, Iowa
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    Figure 1.

    hm2α-SYN-39 transgenic mouse overexpress human synuclein. Slide scanning images (20× objective) of a coronal midbrain section through the substantia nigra stained for TH in green in hm2α-SYN-39 transgenic mice and wild-type (WT) mice at (A) low power (20× objective). B, Subsections from A outlined in white stained for TH in green. C, Same sections as in B stained for human synuclein in red, and (D) merged images with co-stained neurons in yellow. E, Confocal images (40× objective, 8× digital zoom) of synuclein expression in dopaminergic neurons of the substantia nigra from a wild-type mouse and an hm2α-SYN-39 transgenic mouse. Scale bars: A–D, 125 μm; E, 5 μm. F, Western blots from two hm2α-SYN-39 transgenic mice and two WT littermate controls.

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    Figure 2.

    Quantification of TH immunofluorescence in the striatum and substantia nigra is similar in hm2α-SYN-39 and wild-type mice. TH staining (red) from the striatum of (A) wild-type (WT) and (B) hm2α-SYN-39 mice. C, Quantification of TH intensity revealed no consistent differences between genotypes. Similarly, TH from the midbrain of (D) WT and (E) hm2α-SYN-39 mouse. F, Quantification of TH levels revealed no consistent differences between genotypes. Scale bars: A, B and D, E, 1,000 μm. Data from 9 wild-type mice (WT; blue) versus 18 hm2α-SYN-39 mice (red).

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    Figure 3.

    hm2α-SYN-39 transgenic mice do not have reliable behavioral deficits. A, Time on the rotarod and (B) maximum revolutions per minute (rpm). There were no reliable effects of genotype for 9 wild-type mice (WT; blue) versus 20 hm2α-SYN-39 mice (red). C, Open-field distance traveled for WT versus hm2α-SYN-39 mice; there was a main effect of time, genotype, and an interaction due to the hm2α-SYN-39 mice being less active early and hyperactive late in their lives. Points were jittered for visualization.

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Mice Expressing A53T/A30P Mutant Alpha-Synuclein in Dopamine Neurons Do Not Display Behavioral Deficits
Cameron Keomanivong, Josephine Schamp, Ervina Tabakovic, Ramasamy Thangavel, Georgina Aldridge, Andrew A. Pieper, Nandakumar S. Narayanan
eNeuro 13 February 2024, 11 (2) ENEURO.0170-23.2023; DOI: 10.1523/ENEURO.0170-23.2023

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Mice Expressing A53T/A30P Mutant Alpha-Synuclein in Dopamine Neurons Do Not Display Behavioral Deficits
Cameron Keomanivong, Josephine Schamp, Ervina Tabakovic, Ramasamy Thangavel, Georgina Aldridge, Andrew A. Pieper, Nandakumar S. Narayanan
eNeuro 13 February 2024, 11 (2) ENEURO.0170-23.2023; DOI: 10.1523/ENEURO.0170-23.2023
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Keywords

  • animal models
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  • dopamine
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