PT  - JOURNAL ARTICLE
AU  - Mélanie H. Thomas
AU  - Mona Karout
AU  - Beatriz Pardo Rodriguez
AU  - Yujuan Gui
AU  - Christian Jaeger
AU  - Alessandro Michelucci
AU  - Heike Kollmus
AU  - Klaus Schughart
AU  - Djalil Coowar
AU  - Rudi Balling
AU  - Michel Mittelbronn
AU  - Lasse Sinkkonen
AU  - Pierre Garcia
AU  - Manuel Buttini
TI  - Strain- and age-dependent features of the nigro-striatal circuit in three common laboratory mouse strains, C57BL/6J, A/J, and DBA/2J - <em>Implications for Parkinson’s disease modeling</em>
AID  - 10.1101/2020.11.30.404293
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.30.404293
4099  - http://biorxiv.org/content/early/2020/12/01/2020.11.30.404293.short
4100  - http://biorxiv.org/content/early/2020/12/01/2020.11.30.404293.full
AB  - Mouse models have been instrumental in understanding genetic determinants of aging and its crucial role in neurodegenerative diseases. However, few studies have analyzed the evolution of the mouse brain over time at baseline. Furthermore, mouse brain studies are commonly conducted on the C57BL/6 strain, limiting the analysis to a specific genetic background. In Parkinson’s disease, the gradual demise of nigral dopaminergic neurons mainly contributes to the motor symptoms. Interestingly, a decline of the dopaminergic neuron function and integrity is also a characteristic of physiological aging in some species. Age-related nigro-striatal features have never been studied in mice of different genetic backgrounds. In this study, we analyze the morphological features in the striatum of three common mouse strains, C57BL/6J, A/J, and DBA/2J at 3-, 9- and 15 months of age. By measuring dopaminergic markers, we uncover age-related changes that differ between strains and evolve dynamically over time. Overall, our results highlight the importance of considering background strain and age when studying the murine nigro-striatal circuit in health and disease.HighlightsStudy of the integrity of the nigro-striatal circuit in C57BL/6J, A/J, and DBA/2J at different agesAge related evolution of essential features of nigral dopaminergic neurons differ between strainsConsider background strain and age is crutial to study the nigrostriatal circuit in health and diseaseCompeting Interest StatementThe authors have declared no competing interest.AbbreviationsALDH1A1aldehyde dehydrogenase 1 family member A1BSAbovine serum albuminCNScentral nervous systemDATdopamine transporterGC-MSgas chromatography - mass spectrometryMPTP1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinePBSphosphate-buffered salinePDParkinson’s diseasePFAparaformaldehydeSNsubstantia nigra pars compactaTHtyrosine hydroxylase