Evolution of aberrant brain-wide spatiotemporal dynamics of resting-state networks in a Huntington's disease mouse model

被引:0
作者
Vasilkovska, Tamara [1 ,2 ]
Verschuuren, Marlies [2 ,3 ,4 ]
Pustina, Dorian [5 ]
van den Berg, Monica [1 ,2 ]
Van Audekerke, Johan [1 ,2 ]
Pintelon, Isabel [2 ,3 ,4 ]
Cachope, Roger [5 ]
De Vos, Winnok H. [2 ,3 ,4 ]
van der Linden, Annemie [1 ,2 ]
Adhikari, Mohit H. [1 ,2 ]
Verhoye, Marleen [1 ,2 ]
机构
[1] Univ Antwerp, Bioimaging Lab, Univ Pl 1, B-2610 Antwerp, Belgium
[2] Univ Antwerp, NEURO Res Ctr Excellence, Antwerp, Belgium
[3] Univ Antwerp, Lab Cell Biol & Histol, Antwerp, Belgium
[4] Univ Antwerp, Antwerp Ctr Adv Microscopy, Antwerp, Belgium
[5] CHDI Fdn Inc, CHDI Management Inc, Princeton, NJ USA
关键词
astrocytes; biomarkers; Huntington's disease; large-scale brain networks; neurodegeneration; pericytes; quasi-periodic patterns; resting-state fMRI; VEGF; FREQUENCY BOLD FLUCTUATIONS; ENDOTHELIAL GROWTH-FACTOR; FUNCTIONAL CONNECTIVITY; DEFAULT-MODE; VASCULAR REACTIVITY; FMRI; PREMANIFEST; DYSFUNCTION; ASTROCYTES; PERICYTES;
D O I
10.1002/ctm2.70055
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Huntington's disease (HD) is marked by irreversible loss of neuronal function for which currently no availability for disease-modifying treatment exists. Advances in the understanding of disease progression can aid biomarker development, which in turn can accelerate therapeutic discovery. Methods: We characterised the progression of altered dynamics of whole-brain network states in the zQ175DN mouse model of HD using a dynamic functional connectivity (FC) approach to resting-state fMRI and identified quasi-periodic patterns (QPPs) of brain activity constituting the most prominent resting-state networks. Results: The occurrence of the normative QPPs, as observed in healthy controls, was reduced in the HD model as the phenotype progressed. This uncovered progressive cessation of synchronous brain activity with phenotypic progression, which is not observed with the conventional static FC approaches. To better understand the potential underlying cause of the observed changes in these brain states, we further assessed how mutant huntingtin (mHTT) protein deposition affects astrocytes and pericytes - one of the most important effectors of neurovascular coupling, along phenotypic progression. Increased cell-type dependent mHTT deposition was observed at the age of onset of motor anomalies, in the caudate putamen, somatosensory and motor cortex, regions that are prominently involved in HD pathology as seen in humans. Conclusion: Our findings provide meaningful insights into the development and progression of altered functional brain dynamics in this HD model and open new avenues in assessing the dynamics of whole brain states, through QPPs, in clinical HD research.
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页数:24
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