Biology subjects

Peyrard, S.

Publications and source records attributed to Peyrard, S..

6 recordsLinked to original sources

bioRxiv2026

Sex-dependent and region-specific morphological adaptations in astrocytes following early-life stress

Astrocytes are structurally heterogeneous, with cell morphology providing a valuable readout of experi-ence-dependent plasticity. Despite this, single-cell reconstruction including complete cellular territories remains challenging to compare across brain regions and experimental groups. We used unilateral retro-orbital delivery of PHP.eB-GfaABC1D-eGFP as a practical method for sparse astrocyte labeling and ap-plied it to evaluate regional, sex, and early-life-stress comparisons in the mouse amygdala. Systemic vi-rus delivery to broadly target astrocytes across the brain produced eGFP-positive cells throughout cortex, hippocampus, hypothalamus, and amygdala with spatially isolated cells suitable for intensity projection, three-dimensional surface reconstruction, filament tracing, and Sholl analysis. In naive females, we report relatively homogenous morphological features between lateral amygdala and basal amygdala. In naive males, basal amygdala astrocytes had greater volume and a lower surface-area-to-volume ratio, while surface area, soma diameter, territory, and arborization measures did not differ significantly. Interestingly, early-life stress produced sex-specific morphological responses in the basal amygdala. Females showed increased perimeter, area, and Feret diameter without significant changes in three-dimensional volume or resolved filament measures. Males instead showed reduced surface area and volume, with no significant changes in projected territorial dimensions, soma diameter or resolved filament measures. S100{beta}-positive cell density was unchanged in the displayed regional and stress comparisons. These findings es-tablish systemic sparse eGFP labeling as an efficient route to single-cell astrocyte morphometry and re-veal a sex-dependent and region-specific dissociation between territorial expansion and three-dimensional volumetric contraction after early-life stress.

neuroscience↗

bioRxiv2026

TDP-43 pathology is linked to motor neuron loss but is independent of stress granules in vivo

Nuclear depletion and cytoplasmic aggregation of TDP-43 define a pathological signature across amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimers disease, and limbic-predominant age-related TDP-43 encephalopathy (LATE). Stress granule persistence and chronic activation of the integrated stress response (ISR) have been proposed to trigger this pathology, yet clinical trials targeting these pathways have failed despite robust target engagement suggesting that the prevailing model may be incomplete. Here, we use a physiologically relevant recurrent hyperthermia paradigm to directly test the relationship between stress granules and TDP-43 pathology in vivo. We find that RNA-binding proteins typically associated with stress granules persist as dynamic, phase-separated cytoplasmic assemblies in spinal motor neurons of both wild-type and mutant TDP-43 mice. These structures resolve spontaneously and are spatially distinct from TDP-43 puncta. Strikingly, in mutant TDP-43 mice with a compromised acute stress granule response, stress exposure provokes TDP-43 nuclear export and cytoplasmic deposition, culminating in selective loss of spinal -motor neurons after recurrent stress. Our results reveal that TDP-43 nuclear clearance and cytoplasmic aggregation can occur independently of stress granules in vivo, overturning a central assumption of TDP-43 pathogenesis. This paradigm shift reframes the mechanistic link between cellular stress and TDP-43 pathology, providing a new perspective for therapeutic strategies related to ISR modulation.

neuroscience↗

bioRxiv2026

Astrocytic Encoding of Threat in the Basolateral Amygdala

AO_SCPLOWBSTRACTC_SCPLOWThe basolateral amygdala (BLA) has long been implicated in threat detection and the generation of anxiety states. While previous experiments have demonstrated the important role of BLA principal neurons in driving anxiety-related behaviors, population-level recordings suggest that principal neurons encode broad exploratory states rather than anxiety per se. This discrepancy questions whether anxiety is indeed represented within the BLA, or if the BLA reflects a broader representation of behavioral states. Here, using simultaneous in vivo calcium recordings in both astrocytes and principal neurons in the BLA we find that in contrast to neurons, astrocytic activity provides a stable and scalable representation of threat-induced anxiety across an array of behavioral tasks. We find that the magnitude of astrocyte response to threatening stimuli is modulated by the individual anxiety levels of animals, and that exploration of anxiogenic environment can be decoded across multiple tasks using astrocyte activity alone. Our results shed light on a specialized encoding property of BLA astrocytes and establish these cells as key computational elements of threat processing in anxiety circuits.

neuroscience↗

bioRxiv2024

Astrocyte glucocorticoid receptors mediate sex-specific changes in activity following stress

Interactions between orexin neurons and astrocytes in the lateral hypothalamus influence activity levels including circadian and motivated behaviour. These behaviors are disrupted by stress in rodents and form a hallmark of stress-related neuropsychiatric disorders. Here we set out to understand how stress influences activity and the underlying cellular mechanisms. We report that the long-term effects of stress on activity levels correlate with spontaneous firing of orexin neurons with hyperactivity in males and hypoactivity presented by female mice. These neuronal changes were accompanied by extensive astrocyte remodelling. Causal manipulations identified lateral hypothalamic astrocytes as key regulators of activity patterns. In the context of stress, genetic deletion of glucocorticoid receptors in lateral hypothalamic astrocytes rescued the effects of stress on orexin neuron firing, restoring activity to control levels in both males and females. Overall, these data suggest that astrocytic regulation of orexin neuron firing enables the maintenance of activity levels, and their dysfunction drives stress-induced activity dysregulation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/613499v1_ufig1.gif" ALT="Figure 1"> View larger version (71K): org.highwire.dtl.DTLVardef@1e4b3b9org.highwire.dtl.DTLVardef@1d35774org.highwire.dtl.DTLVardef@12a168org.highwire.dtl.DTLVardef@122d9dc_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Astrocyte glucocorticoid signaling mediates cognitive impairment induced by early-life stress

Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. These behavioural changes were associated with impaired synaptic plasticity, increased neural excitability, and astrocyte hypofunction. Genetic perturbation of amygdala astrocyte function by either reducing astrocyte calcium activity or reducing astrocyte network function was sufficient to replicate cellular, synaptic, and fear memory generalisation associated with early-life stress. Our data reveal a role of astrocytes in tuning emotionally salient memory and provide mechanistic links between early-life stress, astrocyte hypofunction, and behavioural deficits. Summary Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/519598v4_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1d9a228org.highwire.dtl.DTLVardef@124ff67org.highwire.dtl.DTLVardef@1fbe186org.highwire.dtl.DTLVardef@19362fb_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

The soybean rust pathogen Phakopsora pachyrhizi displays transposable element proliferation that correlates with broad host-range adaptation on legumes

Asian soybean rust, caused by Phakopsora pachyrhizi, is one of the worlds most economically damaging agricultural diseases. Despite P. pachyrhizis impact, the exceptional size and complexity of its genome prevented generation of an accurate genome assembly. We simultaneously sequenced three P. pachyrhizi genomes uncovering a genome up to 1.25 Gb comprising two haplotypes with a transposable element (TE) content of ~93%. The proliferation of TEs within the genome occurred in several bursts and correlates with the radiation and speciation of the legumes. We present data of clear de-repression of TEs that mirrors expression of virulence-related candidate effectors. We can see a unique expansion in amino acid metabolism for this fungus. Our data shows that TEs play a dominant role in P. pachyrhizis genome and have a key impact on various processes such as host range adaptation, stress responses and genetic plasticity of the genome.

microbiology↗