Biology subjects

Dias, I.

Publications and source records attributed to Dias, I..

3 recordsLinked to original sources

bioRxiv2024

Novel murine closed-loop auditory stimulation paradigm elicits macrostructural sleep benefits in neurodegeneration

Boosting slow-wave activity (SWA) by modulating slow-waves through closed-loop auditory stimulation (CLAS) might provide a powerful nonpharmacological tool to investigate the link between sleep and neurodegeneration. Nevertheless, CLAS in this context was not yet explored. Here, we established mouse CLAS (mCLAS)-mediated SWA enhancement and explored its effects onto sleep deficits in neurodegeneration, by targeting the up-phase of slow-waves in mouse models of Alzheimers (AD, Tg2576) and Parkinsons disease (PD, M83). We found that tracking a 2Hz component of slow-waves leads to highest precision of NREM sleep detection in mice, and that its combination with a 30{degrees} up-phase-target produces a significant SWA 15-30% increase from baseline in WTAD and TGAD mice versus a MOCK group. Conversely, combining 2Hz with a 40{degrees} phase target yields a significant increase ranging 30-35% in WTPD and TGPD mice. Interestingly, these phase-target-triggered SWA increases are not genotype dependent but strain specific. Sleep alterations that may contribute to disease progression and burden were described in AD and PD lines. Notably, pathological sleep traits where rescued by mCLAS, which elicited a 14% decrease of pathologically heightened NREM sleep fragmentation in TGAD mice, accompanied by a steep decrease in microarousal events during both light and dark periods. Overall, our results indicate that model-tailored phase-targeting is key to modulate SWA through mCLAS, prompting the acute alleviation of key neurodegeneration-associated sleep phenotypes and potentiating sleep regulation and consolidation. Further experiments assessing the long-term effect of mCLAS in neurodegeneration may majorly impact the establishment of sleep-based therapies.

neuroscience↗

bioRxiv2023

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo

BackgroundAbnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinsons disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. MethodsFluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using recombinant fibrils and brains from 10-11 months old M83 mice, which subsequently underwent in vivo concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging. The in vivo results were verified against structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 Tesla and scanning transmission X-ray microscopy (STXM) of perfused brains. Brain slice immunofluorescence and Prussian blue staining were further performed to validate the detection of alpha-synuclein inclusions and iron deposition in the brain, respectively. ResultsTHK-565 showed increased fluorescence upon binding to recombinant alpha-synuclein fibrils and alpha-synuclein inclusions in post-mortem brain slices from patients with Parkinsons disease and M83 mice. i.v. administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 minutes post-injection by wide-field fluorescence compared to non-transgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. ConclusionWe demonstrated in vivo mapping of alpha-synuclein by means of non-invasive epifluorescence and vMSOT imaging assisted with a targeted THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

neuroscience↗

bioRxiv2021

Natural age-related sleep-wake alterations onset prematurely in the Tg2576 mouse model of Alzheimer disease

Sleep insufficiency or decreased quality have been associated with Alzheimers disease (AD) already in its preclinical stages. Whether such traits are also present in rodent models of the disease has been poorly addressed, somewhat disabling the preclinical exploration of sleep-based therapeutic interventions for AD. We investigated age-dependent sleep-wake phenotype of a widely used mouse model of AD, the Tg2576 line. We implanted electroencephalography/ electromyography headpieces into 6 months old (plaque-free, n=10) and 11 months old (moderate plaque-burdened, n=10) Tg2576 and age-matched wild-type (WT) mice and recorded vigilance states for 24 hours. Tg2576 mice exhibited significantly increased wakefulness and decreased non-rapid eye movement sleep over a 24-hour period compared to WT mice at 6, but not at 11 months of age. Concomitantly, delta power appeared decreased in 6-month old Tg2576 mice in comparison to age-matched WT controls, yielding a reduced slow-wave energy phenotype in the young mutants. Lack of genotype-related differences over 24 hours in overall sleep-wake phenotype at 11 months of age appears to be the result of the natural aging of WT mice. Therefore, our results indicate that at plaque-free stages of the disease, diminished sleep quality is present in Tg2576 mice which resembles aged healthy controls, suggesting an early-onset of sleep-wake deterioration in murine AD. Whether such disturbances in the natural patterns of sleep could in turn worsen disease progression warrants further exploration.

neuroscience↗