Biology subjects

Butruille, L.

Publications and source records attributed to Butruille, L..

4 recordsLinked to original sources

bioRxiv2026

The olfactory ventricle: an overlooked and evolutionarily conserved feature of the mammalian brain

The olfactory ventricle (OV), an anterior extension of the lateral ventricular system into the olfactory bulbs, is generally considered a transient developmental structure that closes during early postnatal life. However, this view largely derives from a limited number of laboratory models, and the evolutionary distribution and cellular organization of the adult OV remain poorly understood. Here, we combined a comparative survey of mammalian neuroanatomy with phylogenetic analyses and cellular characterization of the OV across species. We compiled anatomical data for 154 mammalian species spanning 26 orders and 80 families, revealing widespread persistence of a patent OV into adulthood. Phylogenetic analyses supported OV presence as the ancestral mammalian state and indicated that its absence is phylogenetically structured and consistent with repeated secondary losses. Chiroptera displayed multiple lineage-specific losses, whereas variation within Muridae extended to the intraspecific level, with contrasting OV persistence among Mus musculus and Rattus norvegicus populations. Comparative histological analyses in sheep, Peromyscus maniculatus, and CD1 mice revealed that, despite marked interspecific differences in OV morphology, the persistent ventricular region retains a conserved cellular organization characterized by progenitor- and glial-associated markers, proliferative cells, immature neuronal populations, and a differentiated apical/ciliary interface. Although these observations do not establish local neuronal production or demonstrate that the OV constitutes an autonomous neurogenic niche, their convergence across species indicates that the persistent adult OV is not simply an anatomically residual lumen but a specialized component of mammalian olfactory bulb organization. Together, our findings identify the OV as an ancestral and widely conserved feature of the mammalian brain and provide an evolutionary and cellular framework for investigating the developmental mechanisms controlling its persistence and its potential contribution to adult olfactory neurogenesis and plasticity.

neuroscience↗

bioRxiv2023

Deleterious functional consequences of perfluoroalkyl substances accumulation into the myelin sheath

Exposure to persistent organic pollutants during the perinatal period is of particular concern because of the potential increased risk of neurological disorders in adulthood. Here we questioned whether exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) could alter myelin formation and regeneration. First, we show that PFOS, and to a lesser extent PFOA, accumulated into the myelin sheath of postnatal day 21 (p21) mice, whose mothers were exposed to either PFOA or PFOS (20mg/L) via drinking water during late gestation and lactation, suggesting that accumulation of PFOS into the myelin could interfere with myelin formation and function. In fact, PFOS, but not PFOA, disrupted the generation of oligodendrocytes, the myelin-forming cells of the central nervous system, derived from neural stem cells localised in the subventricular zone of p21 exposed animals. Then, cerebellar slices were transiently demyelinated using lysophosphatidylcholine and remyelination was quantified in the presence of either PFOA or PFOS. Only PFOS impaired remyelination, a deleterious effect rescued by adding thyroid hormone (TH). Similarly to our observation in the mouse, we also showed that PFOS altered remyelination in Xenopus laevis using the Tg(Mbp:GFP-ntr) model of conditional demyelination and measuring, then, the number of oligodendrocytes. The functional consequences of PFOS-impaired remyelination were shown by its effects using a battery of behavioural tests. In sum, our data demonstrate that perinatal PFOS exposure disrupts oligodendrogenesis and myelin function through modulation of TH action. PFOS exposure may exacerbate genetic and environmental susceptibilities underlying myelin disorders, the most frequent being multiple sclerosis. HighlightsO_LIOur investigation points the deleterious effects of PFOS incorporation into the myelin sheath C_LIO_LIPFOS interfere dramatically with the generation of remyelinating and functional repair of demyelinating lesions C_LIO_LIOur study points to a potential link between these persistent pollutants and the recent increase in prevalence of multiple sclerosis C_LI

pharmacology and toxicology↗

bioRxiv2020

ZIKA virus effects on neuroprogenitors are exacerbated by the main pyriproxyfen metabolite via thyroid hormone signaling disruption

North-Eastern Brazil saw intensive application of the insecticide pyriproxyfen (PPF) during the microcephaly outbreak caused by Zika virus (ZIKV). ZIKV requires the neural RNA-binding protein Musashi-1 to replicate. TH represses MSI1. Being a suspected TH disruptor, we hypothesized that co-exposure to the main metabolite of PPF, 4-OH-PPF, would exacerbate ZIKV effects through increased MSI1 expression. This was tested using in vitro mouse neurospheres and an in vivo TH signaling reporter model, Xenopus laevis. TH signaling was decreased by 4-OH-PPF in both models. In mouse-derived neurospheres the metabolite reduced neuroprogenitor proliferation as well as markers of neuronal differentiation. The results demonstrated that 4-OH-PPF significantly induced MSI1 at both the mRNA and protein level, as well as Fasn mRNA. Other TH target genes were also significantly modified. Importantly, several key genes implicated in neuroprogenitor fate and commitment were not dysregulated by 4-OH-PPF alone, but were in combination with ZIKV infection. These included the neuroprogenitor markers Nestin, Egfr, Gfap, Dlx2 and Dcx. Unexpectedly, 4-OH-PPF decreased ZIKV replication, although only at the fourth and last day of incubation, and RNA copy numbers stayed within the same order of magnitude. However, intracellular RNA content of neuroprogenitors was significantly decreased in the combined presence of the PPF metabolite and ZIKV. We conclude that 4-OH-PPF interferes with TH action in vivo and in vitro, inhibiting neuroprogenitor proliferation. In the presence of ZIKV, TH signaling pathways crucial for cortical development are significantly impacted. This provides another example of viral effects that are exacerbated by drug or pesticide use. Significance statementIn 2015, an increase in children born with unusually small heads (microcephaly) in North-Eastern Brazil was linked to infection with the ZIKA virus. An insecticide with thyroid hormone disruptive properties was used in the same areas. We investigated whether simultaneous exposure to the insecticide could increase viral susceptibility. The main metabolite 4-OH-PPF dysregulated thyroid hormone signaling pathways crucial for brain development in both models used. Neural stem cells proliferated less and contained more Musashi-1, a protein the virus needs to replicate. Infecting stem cells pre-exposed to the endocrine disruptor did not amplify viral replication, but aggravated expression of genes implicated in brain development. Our results suggest the insecticide is particularly deleterious to brain development in areas with ZIKA virus prevalence.

neuroscience↗

bioRxiv2018

The pyriproxyfen metabolite 4’OH- pyriproxyfen disrupts thyroid hormone signaling and enhances Musashi-1 levels in neuroprogenitors

Epidemiological and experimental studies have raised questions as to whether the insecticide pyriproxyfen (PPF) could be implicated in the increased incidence of microcephaly associated with ZIKA infection during pregnancy. This pesticide is documented as a thyroid hormone (TH) disrupting chemical. We investigated whether environmentally relevant amounts of its main metabolite, 4-OH-pyriproxyfen (4-OH-PPF), modified TH signaling and early neuronal development. First, an in silico study revealed strong affinity of 4-OH-PPF to fit the ligand binding pocket of TH receptors (TRs). Further, in vitro assays on human cell lines showed 4OH-PPF (> 3 mg/L) to act as a TR antagonist. Next, using a transgenic Xenopus TH-sensitive reporter system, Tg(thibz:GFP) tadpoles showed that 4OH-PPF (> 10-7 mg/L) displayed TH-disruptive activity and reduced tadpole mobility (> 10-1 mg/L). Exposure to 4OH-PPF significantly reduced Xenopus head size at levels equivalent to the maximum recommended daily intake of PPF (3x 10-1 mg/L). Most strikingly, in both the Xenopus system in vivo and in mouse neurosphere cultures, environmentally relevant concentrations of 4OH-PPF increased expression of the gene encoding an RNA-binding protein that enables ZIKA replication: Musashi-1 (msi1) in neurogenic brain areas. We conclude that first, the PPF metabolite, 4OH-PPF, disrupts thyroid signaling, neuronal development and behavior in Xenopus embryos, and second, that it increases Musashi-1 levels in neurogenic zones of both mouse and Xenopus, creating the potential to enhance viral replication. As PPF is used in areas with high microcephaly incidence and is readily broken down to 4OH-PPF, these findings provide a plausible mechanism whereby PPF could, through modulating expression of Musashi-1, exacerbate the effects of ZIKA virus infection.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC=\"FIGDIR/small/352088_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (23K):\norg.highwire.dtl.DTLVardef@12f397borg.highwire.dtl.DTLVardef@166bbdforg.highwire.dtl.DTLVardef@1b83665org.highwire.dtl.DTLVardef@fb5a30_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗