Biology subjects

Dourte, M.

Publications and source records attributed to Dourte, M..

5 recordsLinked to original sources

bioRxiv2025

An Early Olfactory Transcriptomic Signature of Tauopathy: Gbp2b Emerges as a Candidate Biomarker of Tau-Driven Neuroinflammation

Olfactory dysfunction is increasingly recognized as an early feature of neurodegenerative diseases such as Alzheimers disease. PS19 mice, a well-established tauopathy model, exhibit hallmarks of tau pathology--including hyperphosphorylated tau and pretangle formations--in various regions of the olfactory system. Notably, very recent data demonstrated that aberrantly hyperphosphorylated tau (pTau) was detected as early as 1.5 months of age in the olfactory epithelium (OE). This region contains olfactory sensory neurons projecting to the olfactory bulb (OB), where similar pTau pattern was also observed at this early stage. By 6 months, tau pretangles were evidenced in higher olfactory areas such as the piriform and entorhinal cortices. Given the early involvement of the OE and OB in tau pathology, we performed transcriptomic analyses at 3, 6, and 9 months to investigate the molecular pathways underlying tau pathology in these olfactory regions. Due to the OEs peripheral location and anatomical accessibility, we also aimed in that respect to identify potential early biomarkers of tauopathy. The hippocampus, a key brain region affected in Alzheimers disease and related disorders, was included in the analysis as a comparative reference due to its known vulnerability and clinical relevance. Our analyses revealed region- and age-specific gene expression changes in PS19 mice. Functional enrichment analyses indicated a temporal progression of molecular alterations associated with tau pathology. We identified a subset of genes differentially expressed across different time points and/or regions. Among these, Gbp2b emerged as a particularly promising early biomarker candidate for tauopathy in the OE, showing consistent upregulation across tau pathological stages and brain regions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/662324v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@17148c1org.highwire.dtl.DTLVardef@5fa7dborg.highwire.dtl.DTLVardef@51e21org.highwire.dtl.DTLVardef@1fd4302_HPS_FORMAT_FIGEXP M_FIG Created in BioRender. Kienlen-Campard, P. (2025) https://BioRender.com/k7xoypd C_FIG

neuroscience↗

bioRxiv2025

Napping alters Functional Brain Responses in the Aged

Circadian rhythms shape the temporal organization of sleep and wakefulness and evolve throughout the adult lifespan, leading to higher sleep-wake cycle fragmentation with ageing. The increasing prevalence of daytime napping represents a visible manifestation of such fragmentation and has been suggested to forecast age-related cognitive decline. Here, we assessed the impact of napping on functional brain correlates of performance on a Sternberg working memory (WM) task using functional magnetic resonance imaging in 60 healthy older individuals, prospectively recruited with respect to their napping habits (39 females, age: 59-82y). As compared to non-nappers, nappers showed reduced hemispheric asymmetry in the dorsolateral prefrontal cortex (DLPFC, p< 0.001) and decreased performance at high WM load levels. Only in non-nappers was increased ipsilateral activation in the DLPFC associated with better performance at high WM load levels (p < 0.05), while contralateral activation across all WM load levels was not associated with better performance. These findings indicate that functional brain compensation and dedifferentiation processes vary according to an individuals napping phenotype, potentially serving as a marker of inter-individual differences in cognitive and brain aging.

neuroscience↗

bioRxiv2025

The Olfactory Epithelium: A Critical Gateway for Pathological Tau Propagation and a Target for Mitigating Tauopathy in the Central Nervous System

Olfactory impairment is a recognized early indicator of neurodegenerative diseases (NDs), such as Alzheimers disease (AD). Intracellular aggregates of hyperphosphorylated tau protein, referred to as neurofibrillary tangles (NFTs), are a hallmark of AD. NFTs are found in the olfactory bulb (OB) and entorhinal cortex (EC), both crucial for processing olfactory information. We explored the hypothesis that typical tau lesions could appear early and progress along olfactory regions to reach connected areas critically affected in AD (e.g. EC and hippocampal formation). To that end, we used transgenic PS19 mice expressing mutated human tau protein (1N4R isoform, P301S mutation). They recapitulate major phenotypes of AD, such as accumulation of NFTs, synaptic dysfunction, cognitive impairment, and neuronal loss. The presence of pathological hyperphosphorylated human tau protein (pTau) was monitored in olfactory regions: olfactory epithelium (OE), OB, piriform cortex (PC), and in connected regions of the hippocampal formation (hippocampus and EC). pTau was detected in the OEs middle stratum and in the OBs olfactory nerve layer (ONL) at 1.5 months. At 6 months of age, tau accumulations were found in the PC and EC, along with the CA3 region and dentate gyrus of the hippocampus. We found that olfactory function remained unaffected in PS19 mice, despite the presence of tau pathology in key regions of the olfactory system. Complete stripping of the OE by intranasal administration of ZnSO4 led to a significant reduction in pretangle-like tau pathology within the PC, amygdala, and EC of 6-month-old PS19 mice. Finally, we observed in human post-mortem samples that pTau signal was present in the olfactory regions (OE and OB) of patients at early Braak stages (I/II). Based on these observations, we propose that pTau could appear, due to ageing or environmental agents, in the OE and subsequently spread in a prion-like manner to the hippocampal formation along neuroanatomical connections. These findings also indicate the interest of the OE as a target for intervention aimed at mitigating the progression of tauopathy in the CNS.

neuroscience↗

bioRxiv2024

Afternoon to early evening bright light exposure reduces later melatonin production in adolescents

Whether light exposure during the day reduces non-visual light effects later in the evening has not been studied in adolescents. We investigate whether afternoon-early evening (AEE) light interventions (130 lx, 2500 lx, 4.5 hours, compared to 6.5 lx) would increase melatonin levels during later evening light exposure (130 lx) in a counterbalanced crossover study with 22 adolescents (14-17 years, 11 female). Contrary to our hypothesis, evening melatonin levels decreased after AEE bright light exposure, while sleepiness and vigilance were unaffected, and skin temperature showed no clear changes. The AEE light had acute alerting effects and bright light exposure in the 32 hours before laboratory entry was associated with higher evening melatonin and sleepiness. These findings suggest that bright AEE light increases alertness but may delay melatonin production by interfering with circadian rhythms. The study highlights the complex effects of light timing and its implications for managing adolescents light exposure.

neuroscience↗

bioRxiv2023

Napping and circadian sleep-wake regulation during healthy aging.

Study objectivesDaytime napping is frequently reported among the older population and has attracted increasing attention due to its association with multiple health conditions. Here, we tested whether napping in the aged is associated with altered circadian regulation of sleep, sleepiness and vigilance performance. MethodsSixty healthy older individuals (mean age: 69y., 39 women) were recruited with respect to their napping habits (30 nappers, 30 non-nappers). All participants underwent an in-lab 40-h multiple nap protocol (10 cycles of 80 mins of sleep opportunity alternating with 160 mins of wakefulness), preceded and followed by a baseline and recovery sleep period. Saliva samples for melatonin assessment, sleepiness and vigilance performance were collected during wakefulness and electrophysiological data were recorded to derive sleep parameters during scheduled sleep opportunities. ResultsThe circadian amplitude of melatonin secretion was reduced in nappers, compared to non-nappers. Furthermore, nappers were characterized by higher sleep efficiencies and REM sleep proportion during day-compared to night-time naps. The nap group also presented altered modulation in sleepiness and vigilance performance at specific circadian phases. DiscussionOur data indicate that napping is associated with an altered circadian sleep-wake propensity rhythm and thereby contribute to the understanding of the biological correlates underlying napping and/or sleep-wake cycle fragmentation during healthy aging. Altered circadian sleep-wake promotion can lead to a less distinct allocation of sleep into night-time and/or a reduced wakefulness drive during the day, thereby potentially triggering the need to sleep at adverse circadian phase. SIGNIFICANCE STATEMENTWhile napping has raised increasing interest as a health risk factor in epidemiological studies, its underlying regulation processes in the aged remain largely elusive. Here we assessed whether napping in the older population is associated with physiological and behavioral changes in circadian sleep-wake characteristics. Our data indicate that, concomitant to a reduced circadian amplitude in melatonin secretion, healthy older nappers are characterized by reduced day-night differences in sleep efficiency and more particularly in REM sleep, compared to their non-napping counterparts. These results suggest altered circadian response as a cause or consequence of chronic napping in the aged and thereby contribute to the understanding of nap regulation during healthy aging.

neuroscience↗