Biology subjects

Rabah, Y.

Publications and source records attributed to Rabah, Y..

4 recordsLinked to original sources

bioRxiv2024

Satellite glial cells modulate proprioceptive neuron activity in dorsal root ganglia

Proprioception, the sense of body and limb position, is mediated by proprioceptors and is crucial for important motor functions such as standing and walking. Proprioceptor cell bodies reside within the peripheral dorsal root ganglia (DRG) and are tightly enveloped by satellite glial cells (SGCs). SCGs express a number of Gq protein-coupled receptors (Gq GPCRs), but their functional consequences on proprioceptor activity is unknown. Using a combination of chemogenetics, genetics, Ca2+ imaging, pharmacology, immunohistochemistry, and biochemistry, we provide evidence that SGC Gq GPCR signaling is sufficient to drive purinergic receptor-mediated Ca2+ responses in proprioceptor cell bodies. Our findings suggest a potential role for SGC Gq GPCR signaling in shaping proprioceptor information processing. Furthermore, this demonstration of SGC-induced proprioceptor activation has profound implications with SGC Gq GPCR signaling and purinergic receptors representing potential therapeutic targets for alleviating some proprioceptor and sensorimotor impairments associated with spinal muscular atrophy or Friedreichs ataxia.

neuroscience↗

bioRxiv2023

Long-term memory formation depends on an astrocyte-to-neuron H2O2 signaling

Astrocytes interact with neurons during cognitive processes1. In particular, astrocytes help neurons to fight oxidative stress2, a needed function since active neurons are prone to reactive oxygen species (ROS) damage due to their high mitochondrial activity and relatively poor antioxidant defenses3. ROS also play major physiological functions4,5, but it remains unknown how neuronal ROS signaling is activated during memory formation and if astrocytes play a role in that process. We discovered in Drosophila an astrocyte-to-neuron H2O2 signaling cascade essential for long-term memory formation. Stimulation of astrocytes by acetylcholine induces an intracellular calcium increase that triggers the formation of extracellular O2{degrees}- by astrocytic NADPH oxidase. Superoxide dismutase 3 secreted by astrocytes converts O2{degrees}- into H2O2, which is imported into neurons of the olfactory memory center (the mushroom body), as revealed by in vivo H2O2 imaging using an ultrasensitive sensor. Importantly, SOD3 activity requires Cu2+, which we show is delivered by the neuronal Amyloid Precursor Protein. Furthermore, we found that human amyloid-{beta} peptide, involved in Alzheimers disease, inhibits the astrocytic cholinergic receptor and hampers memory formation by preventing H2O2 import into neurons. These findings could have major implications for the understanding of Alzheimers disease etiology, as soluble synaptic A{beta}42 correlates better with the pattern of cognitive decline in AD than amyloid plaques6, and since early pathology in cholinergic neurons of the basal forebrain predicts memory defects7,8.

neuroscience↗

bioRxiv2022

Glycolysis-derived alanine from glia fuels neuronal mitochondria for memory in Drosophila

Glucose is the primary source of energy for the brain. However, it remains controversial whether, upon neuronal activation, glucose is primarily used by neurons for ATP production, or if it is partially oxidized in astrocytes, as proposed by the astrocyte-neuron lactate shuttle model for glutamatergic neurons. Thus, an in vivo picture of glucose metabolism during cognitive processes is missing. Here, we uncover in Drosophila a glia-to-neuron alanine transfer that sustains memory formation. Following associative conditioning, glycolysis in glial cells produces alanine, which is back-converted into pyruvate in mushroom body cholinergic neurons to uphold their increased mitochondrial needs. Alanine, as a mediator of glia-neuron coupling, could be an alternative to lactate in cholinergic systems. In parallel, a dedicated glial glucose transporter imports glucose specifically for long-term memory, by directly transferring it to neurons for use by the pentose phosphate pathway. Our results demonstrate in vivo the compartmentalization of glucose metabolism between neurons and glial cells during memory formation.

neuroscience↗

bioRxiv2020

Characterization of transgenic mouse lines for selectively targeting glial cells in dorsal root ganglia

The importance of glial cells in the modulation of neuronal processes is now generally accepted. In particular, enormous progress in our understanding of astrocytes and microglia physiology in the central nervous system (CNS) has been made in recent years, due to the development of genetic and molecular toolkits. However, the roles of satellite glial cells (SGCs) and macrophages - the peripheral counterparts of astrocytes and microglia - remain poorly studied despite their involvement in debilitating conditions, such as pain. Here, we characterized in dorsal root ganglia (DRGs), different genetically-modified mouse lines previously used for studying astrocytes and microglia, with the goal to implement them for investigating DRG SGC and macrophage functions. Although SGCs and astrocytes share some molecular properties, most tested transgenic lines were found to not be suitable for studying selectively a large number of SGCs within DRGs. Nevertheless, we identified and validated two mouse lines: (i) a CreERT2 recombinase-based mouse line allowing transgene expression almost exclusively in SGCs and in the vast majority of SGCs, and (ii) a GFP-expressing line allowing the selective visualization of macrophages. In conclusion, among the tools available for exploring astrocyte functions, a few can be used for studying selectively a great proportion of SGCs. Thus, efforts remain to be made to characterize other available mouse lines as well as to develop, rigorously characterize and validate new molecular tools to investigate the roles of DRG SGCs, but also macrophages, in health and disease.

neuroscience↗