Gerasimou, S. | bioRxiv Science

bioRxiv2026

Multimodal Profiling of Repair-associated Immune Dynamics in a Mouse Model of Menstruation

Despite the importance of inflammation to menstruation, we lack detailed understanding of how immune dynamics contribute to endometrial repair. We performed detailed phenotypic characterisation of uterine immune cells using single cell RNA sequencing, flow cytometry and multiplex immunohistochemistry in a mouse model of simulated menstruation. Uterine tissues were collected from age-matched controls or from key phases of menstruation, including tissue breakdown, repair and remodelling. Our findings reveal distinct compositional changes across different phases of menstruation and highlight predominant roles for monocytes, macrophages, and neutrophils in endometrial repair. Immunohistochemistry revealed the spatial association of these myeloid cell subsets with areas of tissue repair and remodelling. Bioinformatic analysis highlighted key roles for monocyte, macrophage and neutrophil signalling during endometrial repair with thrombospondin 1 and secreted phosphoprotein 1 emerging as key signalling pathways. These data significantly advance our understanding of menstrual physiology and identify potential therapeutic targets for menstrual disorders. summaryThis study investigates immune cell dynamics in a mouse model of menstruation, highlighting roles for monocytes, macrophages, and neutrophils in non-fibrotic endometrial repair, and identifies key signalling pathways as potential therapeutic targets for menstrual disorders.

immunology↗

bioRxiv2025

Experience-dependent sharp-wave ripple deficits in an Alzheimer's disease mouse model

Amyloid pathology is a hallmark of Alzheimers disease (AD). Hippocampal sharp-wave ripples (SWRs) play a role in memory consolidation and are impaired in various AD mouse models. However, it remains unclear how experience affects SWRs and how extrinsic signals contribute to SWR generation in AD. Here, by combining behavioral, in vivo electrophysiological and fiber photometry approaches, we show that an experience-dependent increase in hippocampal SWRs is disrupted in male and female 5xFAD mice. In wild-type mice, SWRs during non-rapid eye movement sleep (NREMS) increased after exploring a novel environment and the SWR rate gradually decreased with NREMS episodes and multiple behavioral sessions. However, 5xFAD mice did not show such experience-dependent SWR rate changes. A similar deficit was observed after a novel object recognition test. On the other hand, sleep spindles were intact in 5xFAD mice under all conditions. Since deficits in basal forebrain cholinergic neurons have been implicated in 5xFAD mice and SWRs are regulated by hippocampal cholinergic tone, we examined if hippocampal cholinergic signals could explain experience-dependent SWR deficits. Using fiber photometry and expressing a genetically encoded acetylcholine (ACh) sensor in the hippocampus, we found that ACh dynamics in the hippocampus were intact in 5xFAD mice across sleep-wake cycles, including NREMS, while we also found a negative correlation of infraslow cortical signal power dynamics with hippocampal ACh signals during NREMS regardless of genotypes. These results suggest that experience-dependent SWR deficits stem from non-cholinergic pathological changes.

neuroscience↗