bioRxiv Science⌕ Search

Biology subjects

Vanreusel, V.

Publications and source records attributed to Vanreusel, V..

4 recordsLinked to original sources

Dynamics of brain-fluid circulation are altered in the mature-onset Tet-off APP mouse model of amyloidosis

Alzheimers disease (AD), the most common type of dementia, is an incurable brain disorder characterised by the progressive build-up of toxic amyloid-beta (A{beta}) and tau protein aggregates. AD gradually inflicts cognitive functions of an individual such as memory, thinking, reasoning, and language by degrading synaptic function and the integrity of neuronal networks. It has been recently suggested that the efficacy of different brain-clearance systems like the glymphatic system (GS), involved in the removal of toxic waste and homeostatic balance, plays a key role in the pathology of AD. Moreover, the observed coupling between brain fluid movement and global brain activity implies that an alteration of the neuronal network integrity can impact brain fluid circulation throughout the brain and thereby the efficacy of the GS. Here, we investigated the dynamics of brain fluid circulation in Tet-Off APP (AD) mice, a mature-onset model of amyloidosis in which we have recently shown a deterioration of neuronal network integrity by resting-state fMRI. By utilizing dynamic contrast enhanced-MRI and gadoteric acid (Gd-DOTA) T1 contrast agent injected into the cisterna magna, we demonstrated that brain fluid exchange was significantly altered in 14-month-old AD mice compared to control littermates. More specifically, AD mice showed higher Gd-DOTA accumulation in areas proximal to the injection cite and computational modeling of time courses demonstrated significantly lower inflow time constants relative to the controls. Immunohistochemistry demonstrated abundant amyloid plaque burden in the forebrain of the AD group coinciding with extensive astrogliosis and microgliosis. The neuroinflammatory responses were also found in plaque-devoid regions, potentially impacting brain fluid circulation.

neuroscience↗

An in-vivo digital atlas of the spatially reliable cerebral vasculature in mice

Cerebral vascular abnormalities can have a large impact on brain function and have been frequently detected as a comorbidity in various neuropathologies. The mouse is the most common pre-clinical animal model used to investigate neuropathologies and thus cerebral vascular atlases of this species are indispensable. In particular, an atlas derived from multiple animals and that can address inter-subject variability is still absent. The current study presents a mouse cerebral vascular atlas developed from MR 2D-TOF angiograms acquired from a relatively high number (N=21) of 12 weeks old male C57BL/6 mice. The vascular atlas we present depicts large arteries, veins and sinuses that are more spatially reliable across animals than smaller vessels. The atlas is available for download and contains multiple datasets: i) a cerebral vascular atlas; ii) a digital segmentation of large vessels (arteries and veins); iii) a high resolution T2 anatomical background aligned to the atlas; iv) a skeletonized vascular atlas; and v) a vascular graph model. We suggest that these components provide a very potent analysis tool for mouse fMRI data and that the atlas can be used as a template for multimodal brain imaging studies. To this end, we also demonstrate an explicit application of the atlas for the investigation of vascular influences in resting-state fMRI.

neuroscience↗

Resting brain fluctuations are intrinsically coupled to visual response dynamics

How do intrinsic brain dynamics interact with processing of external sensory stimuli? We sought new insights using functional (f)MRI to track spatiotemporal activity patterns at the whole brain level in lightly anesthetized mice, during both resting conditions and visual stimulation trials. Our results provide evidence that quasiperiodic patterns (QPPs) govern mouse resting brain dynamics. QPPs captured the temporal alignment of global brain fluctuations, anti-correlation of the Default Mode (DMN)- and Task Positive (TPN)-like networks, and activity in neuromodulatory nuclei of the reticular formation. While visual stimulation could trigger a transient spatiotemporal pattern highly similar to intrinsic QPPs, global signal fluctuations and QPPs during rest periods could explain variance in the following visual responses. QPPs and the global signal thus appeared to capture a common arousal-related brain-state fluctuation, orchestrated through neuromodulation. Our findings provide new frontiers to understand the neural processes that shape functional brain states and modulate sensory input processing.

neuroscience↗

Bottom-up sensory processing can decrease activity and functional connectivity in the default mode like network in rats.

The default mode network is a large-scale brain network that is active during rest and internally focused states and deactivates as well as desynchronizes during externally oriented (top-down) attention demanding cognitive tasks. However, it is not sufficiently understood if unpredicted salient stimuli, able to trigger bottom-up attentional processes, could also result in similar reduction of activity and functional connectivity in the DMN. In this study, we investigated whether bottom-up sensory processing could influence the default mode like network (DMLN) in rats. DMLN activity was examined using block-design visual functional magnetic resonance imaging (fMRI) while its synchronization was investigated by comparing functional connectivity during a resting versus a continuously stimulated brain state by unpredicted light flashes. We demonstrated that activity in DMLN regions was decreased during visual stimulus blocks and increased during blanks. Furthermore, decreased inter-network functional connectivity between the DMLN and visual networks as well as decreased intra-network functional connectivity within the DMLN was observed during the continuous visual stimulation. These results suggest that triggering of bottom-up attention mechanisms in anesthetized rats can lead to a cascade similar to top-down orienting of attention in humans and is able to deactivate and desynchronize the DMLN.

neuroscience↗