Priority CommunicationStriatal Overexpression of ΔJunD Resets L-DOPA-Induced Dyskinesia in a Primate Model of Parkinson Disease
Section snippets
Methods and Materials
All experiments were carried out in accordance with both the European Communities Council Directive of November 24, 1986, (86/609/EEC) for the care of laboratory animals and the Institutional Animal Care and Use Committee of University of Texas Southwestern Medical Center, in faculties accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC).
Striatal ΔFosB Protein Predicts the Severity of LID in Parkinsonian Macaques After Repeated L-DOPA Administration
Dopaminergic denervation (MPTP) and L-DOPA administration induced an overall increase in striatal levels of ΔFosB protein measured by western blot. The induction of ΔFosB protein after repeated administration of L-DOPA was significantly higher in the subset of animals developing a dyskinetic response (Figure 1A, 1B). There was a significant main effect of treatment [analysis of variance (ANOVA), F(3,13) = 5.97, p < .01]. Post hoc comparisons with Fisher least significance difference (LSD) test
Discussion
To further establish the translational potential of targeting ΔFosB in LID, we first evaluated whether the correlation previously established in rodents between ΔFosB levels and severity of LID extends to the best nonhuman primate model of PD, the MPTP-lesioned macaque (18, 19). We first confirmed by cloning and sequencing that identical splicing of the FosB gene occurs in the macaque brain as reported previously from human and rodent tissues. We found that sequences of FosB and ΔFosB mRNA are
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Discovery of phenanthridine analogues as novel chemical probes disrupting the binding of DNA to ΔFosB homodimers and ΔFosB/JunD heterodimers
2020, Bioorganic and Medicinal Chemistry LettersA Subpopulation of Striatal Neurons Mediates Levodopa-Induced Dyskinesia
2018, NeuronCitation Excerpt :Inhibition of TRAPed striatal neurons, but not a random set of dMSNs, ameliorated LID. While these results corroborate many studies implicating the striatum in LID (Andersson et al., 1999; Berton et al., 2009; Buck et al., 2010; Cao et al., 2010; Engeln et al., 2016; Westin et al., 2001), our study is the first to establish that a specific and stable subset of striatal neurons mediates LID. Many suspect that LID is the result of excessive dMSN activity, and previous studies have treated dMSNs as a single group modulated during LID.
Expanding the repertoire of L-DOPA's actions: A comprehensive review of its functional neurochemistry
2017, Progress in Neurobiology