2018
DOI: 10.1002/mds.27541
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Progressively disrupted somatodendritic morphology in dopamine neurons in a mouse Parkinson's model

Abstract: Background: Parkinson’s disease is characterized by the progressive loss of dopamine neurons in the substantia nigra, leading to severe motor deficits. Although the disease likely begins to develop years before observable motor symptoms, the specific morphological and functional alterations involved are poorly understood. Objectives: MitoPark mice lack the gene coding for mitochondrial transcription factor A specifically in dopamine neurons, which over time produces a progressive decline of neuronal function… Show more

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Cited by 11 publications
(6 citation statements)
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“…Alterations in dendritic morphology have been previously described in dopamine neurons of SNc from adult (5.5-17 months of age) versus juvenile (2-4 weeks) female mice (Gantz et al, 2011) and by our group in both sexes of MitoPark mice, a genetic animal model PD (Lynch et al, 2018). Here, we measured dendritic morphology of SNc dopamine neurons located along the rostrocaudal and mediolateral axis of the SNc (DV -4.44 to -4.72 mm in the horizontal plane) by filling cells with biocytin included in the recording pipette, conjugating with streptavidin, and performing confocal imaging.…”
Section: Aging Does Not Alter Somatodendritic Morphology Of Snc Dopam...supporting
confidence: 60%
See 1 more Smart Citation
“…Alterations in dendritic morphology have been previously described in dopamine neurons of SNc from adult (5.5-17 months of age) versus juvenile (2-4 weeks) female mice (Gantz et al, 2011) and by our group in both sexes of MitoPark mice, a genetic animal model PD (Lynch et al, 2018). Here, we measured dendritic morphology of SNc dopamine neurons located along the rostrocaudal and mediolateral axis of the SNc (DV -4.44 to -4.72 mm in the horizontal plane) by filling cells with biocytin included in the recording pipette, conjugating with streptavidin, and performing confocal imaging.…”
Section: Aging Does Not Alter Somatodendritic Morphology Of Snc Dopam...supporting
confidence: 60%
“…An additional factor that could result in smaller postsynaptic D2 currents is a reduction in somatodendritic morphology in aged males. We previously showed a severely retracted cellular phenotype that worsens with age in the MitoPark mouse model of Parkinson’s disease (Lynch et al, 2018). However, to our knowledge no previous study has analyzed branching parameters in SNc dopamine neurons across the entire lifespan.…”
Section: Discussionmentioning
confidence: 99%
“… Tfam loxP/loxP ; DAT-cre; Parkin −/− : no Parkin-dependent effect on mitochondrial aggregates, mitochondrial morphology, locomotion, or TH-positive cell loss in SNc. ( 163 , 164 , 166 , 235 , 236 ) PD-mito-PstI DAT promoter-driven tetracycline transactivator protein (tTA) Inducible mito-PstI exclusively in DA neurons Expression of tetracycline-sensitive mitochondria-targeted restriction enzyme, Pst I, in DA neurons Mitochondrial matrix localization—COX8A MTS Mito-targeted restriction enzyme damages mtDNA in DA neurons Neuronal phenotype: progressive degeneration of the DA population within SNc, striatal dopamine depletion, age-dependent loss of TH-positive neurons, L-DOPA reversible motor deficit. Locomotor deficits precede TH-positive cell loss.…”
Section: In Vivo Models For Proof-of-mechanism and Proof-of-mentioning
confidence: 99%
“…We next sought to determine if differences in somatodendritic morphology could contribute to reduced D2 receptor currents in old males. Altered dendritic morphology has been described in SNc dopamine neurons from adult (5.5-17 months of age) versus juvenile (2-4 weeks) female mice 44 and by our group in both sexes of MitoPark mice, a genetic animal model of PD 45 . Here, we measured dendritic morphology of male SNc dopamine neurons located along the rostrocaudal and mediolateral axis of the SNc (DV −4.44 to −4.72 mm in the horizontal plane) by filling cells with biocytin included in the recording pipette, conjugating with streptavidin, and performing confocal imaging.…”
Section: D2-ipsc Enhancement By the Stress Neuropeptide Crf Is Not Af...mentioning
confidence: 62%