Biology subjects

Vilademunt, M.

Publications and source records attributed to Vilademunt, M..

4 recordsLinked to original sources

bioRxiv2026

Intra-uterine position modulates lifelong hippocampal neurogenesis and anxiety-related behavior

Individual differences in vulnerability to disease are a defining feature of biology and are especially prominent in mood disorders, where susceptibility to stress varies markedly across individuals. Strikingly, such individuality also emerges in inbred mice despite genetic homogeneity and controlled environments, suggesting that early non-genomic factors can durably shape behavioral trajectories. Yet the developmental origin of this variability remains largely unknown. Here, we identify the intra-uterine position (IUP) as a potent source of inter-individual variability in emotional behavior by showing that it influences prenatal steroid exposure, hippocampal development, adult neurogenesis, and anxiety-like traits in inbred mice. At embryonic day 18.5, embryos adjacent to one or two male siblings (i.e. 1M/2M) exhibited altered brain steroid profiles, coinciding with increased proliferation of neural stem and progenitor cells in the dentate gyrus, as compared to 0M mice. Single-nucleus RNA sequencing further revealed that IUP leaves a transcriptional imprint on hippocampal development, with 1M/2M neural stem cells showing reduced stemness and activation of a neurogenic transcription program. In adulthood, 1M/2M mice presented reduced hippocampal and dentate gyrus volumes, diminished radial-glia-like cell counts, lower cell proliferation, and impaired dendritic maturation of immature neurons. Behaviorally, both juvenile (PND22) and young adult (8-week) 1M/2M mice displayed increased trait anxiety, and 1M/2M males exhibited heightened stress reactivity. In vitro, testosterone, but not progesterone, directly enhanced proliferation of adult rat hippocampal stem/progenitor cells, whereas corticosterone reduced it. In vivo, administration of the androgen receptor agonist dihydrotestosterone (DHT) to pregnant dams recapitulated IUP effects by increasing embryonic dentate gyrus (DG) proliferation in female embryos, whereas antagonism reduced progenitor proliferation in male embryos. Together, these results indicate that IUP has long-lasting effects on hippocampal development and anxiety and may underlie natural variations in trait anxiety.

neuroscience↗

bioRxiv2026

The astrocytic secretome increases adult hippocampal neurogenesis and spatial memory in health and disease

INTRODUCTION: Adult hippocampal neurogenesis (AHN) plays an important role in memory and is regulated by astrocytes. Since astrocytic function deteriorates with pathological ageing and Alzheimers disease (AD), we hypothesize that the astrocytic secretome may rescue AHN and cognition. METHODS: We tested the effect of astrocyte-conditioned solution (ACS) on AHN and memory performances in young and aged mice and in two models of AD. RESULTS: ACS increased AHN and improved performance in the object location test in young and aged wild-type mice. In THY-Tau22 mice, a model of tau pathology, ACS restored AHN and cognitive performance. In APP/PS1 mice, a model of amyloid pathology, ACS reduced gliogenesis, and rescued deficits in AHN and spatial memory. In addition, ACS attenuated circulating pro-inflammatory cytokines and the reaction of plaque-associated microglia. DISCUSSION: The astrocytic secretome is a promising, niche-targeted strategy to enhance hippocampal plasticity and memory across ageing and AD.

neuroscience↗

bioRxiv2024

Astrocyte-derived PEA116 increases adult hippocampal neurogenesis and confers stress resilience

In the dentate gyrus of the hippocampus, the neurogenic niche regulates several steps of adult neurogenesis, from the proliferation to the integration of newly formed neurons in the hippocampal network. However, the role of astrocytes in the regulation of adult neural stem cell (aNSC) proliferation is still little described. Here, we found that blocking vesicular release from astrocytes decreased cell proliferation in the dentate gyrus, resulting in impaired adult neurogenesis. Inversely, astrocyte-conditioned medium increased cell proliferation in a vesicular release-dependent manner. We identified PEA116 as a peptide released by astrocytes, that is derived from the c-terminal portion of the PEA15 protein and increased cell proliferation. PEA116 increased ERK2 phosphorylation, decreased the expression of genes involved in aNSC quiescence, resulting in aNSC quiescence exit. The ensuing increase in hippocampal neurogenesis improved resilience to chronic stress. These findings highlight a novel peptide produced by astrocytes that regulates the early steps of adult neurogenesis, with an implication for mood disorders.

neuroscience↗

bioRxiv2022

Postnatal environmental enrichment enhances memory by shaping hippocampal-prefrontal theta and gamma rhythms in diploid and trisomic female mice

Rich social, physical, and cognitively stimulating lifestyles have powerful effects on cognitive abilities, especially when they are experienced early in life. Cognitive therapies are widely used to attenuate cognitive impairment due to intellectual disability, but also aging and neurodegeneration, however the underlying neural mechanisms are poorly understood. Here we investigated the neural substrates of memory amelioration induced by postnatal environmental enrichment (EE) in diploid female mice and Ts65Dn female mice with partial trisomy of genes ortholog to human chromosome 21, a standard model of Down syndrome (DS, trisomy 21). We recorded neural activities in two brain structures key for cognitive function, the hippocampus and the prefrontal cortex, during rest, sleep and memory performance in mice reared in standard or enriched environments for 7 weeks post-weaning. We found that EE shaped hippocampal- prefrontal neural dynamics in diploid mice and rescued the same disrupted pathways in Ts65Dn mice. The neural activity changes detected in EE-reared wild-type mice combined task-independent adjustments (augmented hippocampal pyramidal activity and gamma synchrony across different brain states) and memory-dependent adjustments (enhanced theta-gamma coupling and ripples in the HPC). Therefore, both brain state adjustments and memory-associated adjustments are good candidates to underlie the beneficial effects of EE on cognition in diploid female mice. Concomitantly, EE attenuated hippocampal and prefrontal hypersynchrony in trisomic females, suggesting distinct neural mechanisms for the generation and rescue of healthy and pathological brain synchrony, respectively, by EE. These results put forward hippocampal hypersynchrony and hippocampal-prefrontal miscommunication as major neural mechanisms underlying the beneficial effects of EE for intellectual disability in DS.

neuroscience↗