Biology subjects

Hugel, S.

Publications and source records attributed to Hugel, S..

4 recordsLinked to original sources

bioRxiv2026

Neonatal oxytocin prevents sex-specific spatial memory deficits induced by maternal separation through restoration of hippocampal synaptic plasticity in males

BackgroundStress during critical developmental periods causes lasting neurobiological alterations. Rodent models like neonatal maternal separation (NMS) induce cognitive alterations, particularly spatial memory deficits. Oxytocin (OT) system has been suggested to underlie these consequences, as it is critical for neurodevelopment. This neuropeptide also promotes maternal nurturing, prevents neuroinflammation and displays anxiolytic properties. This study hypothesized that early postnatal OT administration could prevent NMS-induced memory alterations in adult rats. MethodsSprague-Dawley rat pups (both sexes, n=8-12/group) underwent NMS with concomitant intraperitoneal OT injections. At adulthood, novel object recognition and object location tasks were performed. Further investigation was conducted through ex vivo electrophysiological recordings of functional plasticity at Schaffer collateral-CA1 synapses (male, n=7-12/group), alongside RT-qPCR of synaptic, GABAergic, neuro-inflammatory, and oxytocin receptor markers in dorsal CA1 (male, n=4-6/group). ResultsNMS induced male-specific spatial memory impairment without affecting recognition memory. Early OT completely prevented spatial memory deficits in NMS males. Electrophysiological recordings revealed that NMS suppressed CA1 long-term potentiation (LTP), and neonatal OT restored it. NMS induced transcript overexpression of neuro-inflammatory markers, GABAergic markers, and synaptic proteins in dorsal CA1. OT treatment normalized or reduced these mRNA expressions, consistent with restoration of CA1 synaptic function. ConclusionEarly postnatal OT prevents NMS-induced spatial memory deficits and hippocampal LTP impairments in male rats, which is associated with normalized or reduced neuro-inflammatory and GABAergic transcript expressions. These findings establish exogenous oxytocin administration during a critical neonatal window as sufficient to prevent male-specific hippocampal dysfunction and cognitive deficits induced by early-life stress, identifying the oxytocinergic system as a promising target for early neuroprotective interventions.

neuroscience↗

bioRxiv2026

Endoplasmic reticulum membrane contact sites coordinate exocytic site assembly and activity in neuroendocrine cells

Membrane contact sites (MCS) between intracellular organelles regulate lipid exchange, organelles dynamics and spatial organization of signaling pathways, yet their contribution to regulated exocytosis remains poorly understood. Here, we investigated the role of endoplasmic reticulum (ER) MCS in calcium-regulated exocytosis using primary bovine chromaffin cells. Combining electron microscopy on plasma membrane (PM) sheets with immunogold labeling, we identified ER structures contacting docked secretory granules and classified three types of MCS: ER-PM, ER-granule and tripartite ER-PM-granule contacts. These contacts are enriched at exocytic sites and contain Orai1 and STIM1, both known for mediating store-operated calcium release. Functional perturbation of the Orai/STIM pathway revealed that constitutive STIM activation or pharmacological inhibition of Orai1 reduced the number of exocytotic events, slowed catecholamine release and disrupted actin organization at granule docking sites. Together, our findings revealed a previously unrecognized role for ER MCS in organizing exocytic sites and controlling secretion efficiency in neuroendocrine cells.

cell biology↗

bioRxiv2022

The basolateral amygdala-anterior cingulate pathway contributes to depression and its comorbidity with chronic pain

While depression and chronic pain are frequently comorbid, underlying neuronal circuits, and their relevance for the understanding of psychopathology, remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. In naive animals, we demonstrate that activation of this pathway is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, a hub gene significantly upregulated in both mice and humans in the context of altered mood, is necessary for the emergence of depressive-like behaviors. Overall, these results place the BLA-ACC pathway at the core of pain and depression comorbidity, and unravel the role of impaired myelination and Sema4a in mood control.

neuroscience↗

bioRxiv2022

Dissecting the autism-associated 16p11.2 locus identifies multiple drivers in brain phenotypes and unveils a new role for the major vault protein

Using mouse genetic studies, we set out to identify which of the 30 genes causes brain size and other NeuroAnatomical Phenotypes (NAPs) at the autism-associated 16p11.2 locus. We show that multiple genes mapping to this region interact to regulate brain size in contrast to previous studies, with female significantly less affected. Major Vault Protein (MVP), the main component of the vault organelle, is a highly conserved protein found in higher and lower eukaryotic cells, yet its function is not understood. Here we find MVP expression highly specific to the limbic system and Mvp as the top driver gene of NAPs, regulating the morphology of neurons, postnatally and specifically in male. Finally, we demonstrate that the double hemideletion Mvp::Mapk3 rescues NAPs, increases phosphorylation of ERK and alters behavioral performances, suggesting that MVP and ERK share the same signalling pathway, in vivo. Our results highlight that sex-specific cellular and neuroanatomical mechanisms must be considered in neurological disorders such as autism. Most importantly, it provides the first evidence for the involvement of the vault organelle in the regulation of the mammalian brain size and limbic structures.

genetics↗