Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington’s disease
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Le résumé fourni par la source
BACKGROUND: Huntington's disease (HD) is marked by a CAG-repeat expansion in the huntingtin gene that causes neuronal dysfunction and loss, affecting mainly the striatum and the cortex. Alterations in the neurovascular coupling system have been shown to lead to dysregulated energy supply to brain regions in several neurological diseases, including HD, which could potentially trigger the process of neurodegeneration. In particular, it has been observed in cross-sectional human HD studies that vascular alterations are associated to impaired cerebral blood flow (CBF). To assess whether whole-brain changes in CBF are present and follow a pattern of progression, we investigated both resting-state brain perfusion and vascular reactivity longitudinally in the zQ175DN mouse model of HD. METHODS: Using pseudo-continuous arterial spin labelling (pCASL) MRI in the zQ175DN model of HD and age-matched wild-type (WT) mice, we assessed whole-brain, resting-state perfusion at 3, 6 and 9 and 13 months of age, and assessed hypercapnia-induced cerebrovascular reactivity (CVR), at 4.5, 6, 9 and 15 months of age. RESULTS: We found increased perfusion in cortical regions of zQ175DN HET mice at 3 months of age, and a reduction of this anomaly at 6 and 9 months, ages at which behavioural deficits have been reported. On the other hand, under hypercapnia, CBF was reduced in zQ175DN HET mice as compared to the WT: for multiple brain regions at 6 months of age, for only somatosensory and retrosplenial cortices at 9 months of age, and brain-wide by 15 months. CVR impairments in cortical regions, the thalamus and globus pallidus were observed in zQ175DN HET mice at 9 months, with whole brain reactivity diminished at 15 months of age. Interestingly, blood vessel density was increased in the motor cortex at 3 months, while average vessel length was reduced in the lateral portion of the caudate putamen at 6 months of age. CONCLUSION: Our findings reveal early cortical resting-state hyperperfusion and impaired CVR at ages that present motor anomalies in this HD model, suggesting that further characterization of brain perfusion alterations in animal models is warranted as a potential therapeutic target in HD.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington’s disease
- Date Crossref
- 16/04/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Antwerp Bio-Imaging Lab pays non établi dans la noticeUniversité ou école supérieure
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Leiden University Medical Center C.J. Gorter MRI Center pays non établi dans la noticeOrganisme public
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Inserm pays non établi dans la noticeOrganisme public
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Grenoble Institute of Neurosciences pays non établi dans la noticeStructure de recherche
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Université Grenoble Alpes pays non établi dans la noticeUniversité ou école supérieure
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CHDI Foundation pays non établi dans la noticeOrganisation à but non lucratif
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Takeda (Japan) pays non établi dans la noticeEntreprise
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Cajal Therapeutics (United States) pays non établi dans la noticeEntreprise
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Universiteitsplein 1 Antwerp Centre for Advanced Microscopy pays non établi dans la noticeUniversité ou école supérieure
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Grenoble Institut Neurosciences U1216 pays non établi dans la noticeStructure de recherche
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Inc. CHDI Management pays non établi dans la noticeEntreprise
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Present Address: Takeda Pharmaceuticals pays non établi dans la noticeInstitution
Bio-Imaging Lab — University of Antwerp, C.J. Gorter MRI Center — Leiden University Medical Center et Inserm, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.