Biology subjects

Bemelmans, A.

Publications and source records attributed to Bemelmans, A..

6 recordsLinked to original sources

bioRxiv2026

Astrocytes control oxytocin-based maternal behavior via connexin 30

Prosocial and affiliative behaviors rely on complex neuroendocrine neuronal circuits. Dynamic neuroglial interactions play prominent roles in shaping synaptic networks, whose alterations contribute to psychiatric disorders associated with social deficits. However, a role for astrocytes in regulating maternal behavior remains elusive. Here we show that female mice exhibiting increased oxytocin levels in the hypothalamic supraoptic nucleus upon social interactions with pups display neuroglial structural plasticity and downregulation of astroglial connexin 30, a protein involved in morphological remodeling. We found that impairing astroglial connexin 30 expression alters the structural properties of astrocytes by decreasing their volume and coverage of oxytocinergic synapses in the supraoptic nucleus of female mice. This functionally sets levels of plasma oxytocin and maternal behavior, exacerbating maternal care in virgin pup-naive female mice deficient for astroglial Cx30. Hypothalamic astrocytes, via connexin 30, are thus key determinants of oxytocin-based maternal behavior, whose alteration is known to impair social skills development in offspring.

neuroscience↗

bioRxiv2025

Local translation controls early reactive changes in perisynaptic astrocyte processes at pre-symptomatic stages of Alzheimer s disease

Early synaptic dysfunction is a hallmark of Alzheimers disease (AD), yet the astrocytic mechanisms underlying these alterations remain poorly defined. Here, we identify astrocyte perisynaptic processes (PAPs) as subcellular hotspots of early translational dysregulation in AD. Soluble A{beta}-2 rapidly enhanced global and local protein synthesis in primary astrocytes. In 5.5-month-old APP/PS1-dE9 (APP) mice, translating ribosome affinity purification (TRAP) revealed widespread remodeling of the PAP translatome, while whole-astrocyte translation remained largely unchanged. Dysregulated mRNAs were linked to neuroinflammation, synaptic remodeling, and endoplasmic reticulum stress, and alterations emerged prior to amyloid plaque deposition. Among them, Serpina3n exhibited increased mRNA abundance in PAPs, uncovering spatially restricted translational control. Mechanistically, early Serpina3n upregulation was partially driven by JAK-STAT3 signaling, with preferential effects in astrocyte processes. These findings reveal that local translation in astrocyte PAPs is an early and compartment-specific mechanism that may contribute to synaptic dysfunction and disease initiation in AD.

neuroscience↗

bioRxiv2025

Astroglial deficiency for oligophrenin-1 contributes to intellectual disability

Neurodevelopmental disorders, including X-linked intellectual disability, autism spectrum disorder or schizophrenia, can result from the mutation of oligophrenin-1 (Ophn1), encoding a Rho-GTPase-activating protein. Ophn1 regulates synaptic development and function, in part via cytoskeleton reorganization, and is expressed in both neurons and astrocytes. Despite the crucial role of astrocytes in synapse function, altered in neurodevelopmental disorders, and their Ophn1 expression, the specific impact of astroglial Ophn1 deficiency on synaptic transmission and behavior remains unknown. Here, we show that Ophn1 deficiency postnatally in hippocampal astrocytes impairs synaptic transmission, short-term plasticity and spatial working memory in adults. This involves an adenosine A1 receptor-dependent presynaptic mechanism associated with astroglial morphological rearrangements resulting in increased astroglial synapse coverage. The structural, functional and behavioral alterations induced by astroglial Ophn1 deficiency are rescued in adults by pharmacological inhibition of the RhoA/ROCK pathway. Our findings uncover an important role for astroglial Ophn1 deficiency in synaptic and behavioral dysfunctions, pointing to a novel cellular therapeutic target for neurodevelopmental disorders.

neuroscience↗

bioRxiv2021

Nanoscale organization and calcium influx in dendritic spines guarantee ER store refilling without depletion

Dendritic spines are critical components of the neuronal synapse as they receive and transform the synaptic input into a succession of biochemical events regulated by calcium signaling. The spine apparatus (SA), an extension of smooth endoplasmic reticulum (ER), regulates slow and fast calcium dynamics in spines. Calcium release events from SA result in a rapid depletion of calcium ion reservoir, yet the next cycle of signaling requires replenishment of SA calcium stores. How dendritic spines achieve this without triggering calcium release remains unclear. Using computational modeling, calcium and STED super-resolution imaging, we showed that the refilling of calcium-deprived SA involves store-operated calcium entry during spontaneous calcium transients in spine heads. We identified two main conditions that guarantee SA replenishment without depletion: (1) a small amplitude and slow timescale for calcium influx, and (2) a close proximity between SA and plasma membranes. Thereby, molecular nano-organization creates the conditions for a clear separation between SA replenishment and depletion. We further conclude that the nanoscale organization of SA receptors underlies the specificity of calcium dynamics patterns during the induction of long-term synaptic changes.

neuroscience↗

bioRxiv2021

The JAK2-STAT3 pathway controls a beneficial proteostasis response of reactive astrocytes in Huntington disease

Huntingtons disease is a fatal neurodegenerative disease characterized by striatal neurodegeneration, aggregation of mutant Huntingtin and the presence of reactive astrocytes. Astrocytes are important partners for neurons and engage in a specific reactive response in Huntingtons disease that involves morphological, molecular and functional changes. How reactive astrocytes contribute to Huntingtons disease is still an open question, especially because their reactive state is poorly reproduced in experimental mouse models. Here, we show that the JAK2-STAT3 pathway, a central cascade controlling astrocyte reactive response, is activated in the putamen of Huntingtons disease patients. Selective activation of this cascade in astrocytes through viral gene transfer reduces the number and size of mutant Huntingtin aggregates in neurons and improves neuronal defects in two complementary mouse models of Huntingtons disease. It also reduces striatal atrophy and increases glutamate levels, two central clinical outcomes measured by non-invasive magnetic resonance imaging. Moreover, astrocyte-specific transcriptomic analysis shows that activation of the JAK2-STAT3 pathway in astrocytes coordinates a transcriptional program that increases their intrinsic proteolytic capacity, through the lysosomal and ubiquitin-proteasome degradation systems. This pathway also enhances their production and exosomal release of the co-chaperone DNAJB1, which contributes to mutant Huntingtin clearance in neurons. Together, our results show that the JAK2-STAT3 pathway controls a beneficial proteostasis response in reactive astrocytes in Huntingtons disease, which involves bi-directional signalling with neurons to reduce mutant Huntingtin aggregation, eventually improving disease outcomes.

neuroscience↗

bioRxiv2020

Physiological synaptic activity and recognition memory are fueled by astroglial glutamine

Presynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a novel fluorescent probe that tracks glutamine in live cells, which provided direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap-junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes.

neuroscience↗