Biology subjects

Borges, G.

Publications and source records attributed to Borges, G..

5 recordsLinked to original sources

bioRxiv2025

Spared nerve injury induces long-term and brain region-specific changes in oligodendrocyte density in mice

BackgroundEmerging evidence suggests a role for non-neuronal cells in the pathophysiology of chronic pain. Chronic pain causes profound alterations of the transcriptomic program of oligodendroglia, but the effect of pain on the oligodendroglial cells themselves remains unknown. MethodsMale and female C57BL6/J mice underwent spared nerve injury (SNI). Mechanical hypersensitivity was assessed five weeks later using the von Frey test. Six weeks post-surgery, mice were perfused, brains dissected, and immunostained for oligodendrocyte precursors cells (OPC) and mature oligodendrocytes (OL) in four brain regions involved in pain chronification: anterior cingulate cortex (ACC), central amygdala (CeA), basolateral amygdala (BLA), and periaqueductal gray (PAG). ResultsWe found OL were reduced in the ACC and CeA of both sexes six weeks after SNI. Conversely, BLA OL were increased in both sexes following SNI. There was a sex-dependent effect of SNI on PAG-OL, where OL were only reduced in females. SNI did not affect OPC in any of the studied brain regions, but female PAG and BLA appeared to have fewer OPC than males independent of SNI. ConclusionLong-term nerve injury differentially affects OL in a brain region- and sex-dependent manner. This effect is observable six weeks after injury, suggesting a long-lasting impact of chronic pain on oligodendroglial cells. OPC, on the other hand, are remarkably stable. This finding aligns with previous literature showing OPC maintain homeostasis, even in pathological conditions. SignificanceOligodendrocytes ensheathe axons to increase conduction speed, stabilize neuronal connections, and fine-tune neuron-to-neuron communication. Furthermore, pharmacological stimulation of myelination improves pain-induced cognitive deficits in mice, suggesting therapeutic potential in targeting oligodendrocytes in pain. A better understanding of how pain impacts oligodendroglia is thus crucial to better understand the pathophysiology of pain and identify new therapeutic targets.

neuroscience↗

bioRxiv2024

Monandrous flies do remate: plastic and evolutionary consequences of heat exposure on mating behaviour and fertility in Drosophila subobscura

Recent work has reinforced the importance of fertility in predicting population persistence under global warming, especially male fertility. However, most studies on mating and reproductive performance have used as model organism polyandrous species, remaining unclear if and how will monandrous species respond. This is unfortunate as one could expect monandrous species to be particularly susceptible, given their inability to use sperm from multiple males to prevent reduced progeny production due to male sterility. It could be that monandrous females can overcome this toll in fertility by plastically changing their mating rate, or that monandrous populations evolve the ability to remate upon repeated exposure to heat. To test this, we studied the real-time evolution as well as the thermal plastic response of two geographically distinct populations of the monandrous species Drosophila subobscura after 45 generations evolving under a warming scenario. We assessed the impact of heat on male mating behaviour and fertility, as well as the impact of reduced male fertility on female mating behaviour and fertility. We found that in males the toll in mating behaviour due to heat can be recovered with time, whereas that in reproductive success cannot. On the other hand, females exposed to heat-stressed males significantly increased their remating rate, allowing to recover considerably their own reproductive success. Interestingly, most responses were plastic, with no striking effect of adaptation to warming nor of geographical origin. Our work brings new insights into the effects of heat on monandrous species and establishes a model to study how a shift in mating system may affect species ability to respond to climate change.

evolutionary biology↗

bioRxiv2023

Endogenous opioids gate the locus coeruleus pain generator

The locus coeruleus (LC) plays a paradoxical role in chronic pain. Although largely known as a potent source of endogenous analgesia, increasing evidence suggests injury can transform the LC into a chronic pain generator. We sought to clarify the role of this system in pain. Here, we show optogenetic inhibition of LC activity is acutely antinociceptive. Following long-term spared nerve injury, the same LC inhibition is analgesic - further supporting its pain generator function. To identify inhibitory substrates that may naturally serve this function, we turned to endogenous LC mu opioid receptors (LC-MOR). These receptors provide powerful LC inhibition and exogenous activation of LC-MOR is antinociceptive. We therefore hypothesized that endogenous LC-MOR-mediated inhibition is critical to how the LC modulates pain. Using cell type-selective conditional knockout and rescue of LC-MOR receptor signaling, we show these receptors bidirectionally regulate thermal and mechanical hyperalgesia - providing a functional gate on the LC pain generator.

neuroscience↗

bioRxiv2022

Neuropathic injury drives a generalized negative affective state in mice

Neuropathic pain causes both sensory and emotional maladaptation. Preclinical animal studies of neuropathic pain-induced negative affect could result in novel insights into the mechanisms of chronic pain. Modeling pain-induced negative affect, however, is variable across research groups and conditions. The same injury may or may not produce robust negative affective behavioral responses across different species, strains, and laboratories. Here we sought to identify negative affective consequences of the spared nerve injury model on C57BL/6J male and female mice. We found no significant effect of spared nerve injury across a variety of approach-avoidance, hedonic choice, and coping strategy assays. We hypothesized these inconsistencies may stem in part from the short test duration of these assays. To test this hypothesis, we used the homecage-based Feeding Experimentation Device version 3 to conduct 12-hour, overnight progressive ratio testing to determine whether mice with chronic spared nerve injury had decreased motivation to earn palatable food rewards. Our data demonstrate that despite equivalent task learning, spared nerve injury mice are less motivated to work for a sugar pellet than sham controls. Further, when we normalized behavioral responses across all the behavioral assays we tested, we found that a combined normalized behavioral score is predictive of injury-state and significantly correlates with mechanical thresholds. Together these results suggest that homecage-based operant behaviors provide a useful platform for modeling nerve injury-induced negative affect and that valuable pain-related information can arise from agglomerative data analyses across behavioral assays - even when individual inferential statistics do not demonstrate significant mean differences.

neuroscience↗

bioRxiv2022

Sustained spinal motor activity triggered by direct mechanosensory stimulation in adult Drosophila melanogaster

Most vertebrates and invertebrates such as Drosophila melanogaster are able to move in complex environments due to their ability to integrate sensory information along with motor commands. Mechanosensory structures exist along each leg to assist in motor coordination by transmitting external cues or proprioceptive information to motor centers in the central nervous system. Nevertheless, how different mechanosensory structures engage these locomotor centers and their underlying circuits remains poorly understood. Here, we tested the role of mechanosensory structures in movement initiation by optogenetically stimulating specific classes of leg sensory structures. We found that stimulation of leg Mechanosensory Bristles (MsB) and femoral Chordotonal Organ (ChO) is sufficient to initiate forward movement in immobile animals. While the stimulation of the ChO required brain centers to induce forward movement, unexpectedly, brief stimulation of leg MsB triggered sustained cyclic motor activity dependent only on circuits within the Ventral Nerve Cord (VNC). The duration of the MsB-induced movement was dependent on the number of excited cells and specific to leg afferents, since stimulation of MsB in other segments lead to different motor outcomes. MsB-mediated movement lacked inter and intra-leg coordination, but preserved antagonistic muscle activity within joints. Our data shows that sensory stimulation can act in combination with descending commands in order to elicit a faster response to mechanical stimulation. In addition, it sheds light on the ability of specific sensory circuits to modulate motor control, including initiation of movement, presenting a new system to better understand how different levels of coordination are controlled by VNC and central brain locomotor circuits. Significance StatementSensory feedback is critical to allow smooth and stable locomotion. Proprioceptors interact directly with pre-motor centers optimizing and sustaining coordinated movement. However, initiation of moment is considered to be triggered by higher-order centers in the brain. Here we took advantage of the genetic toolkit provided by the fruit fly Drosophila melanogaster to optogenetically activate different classes of leg sensory cells in immobile animals. We found that leg mechanosensory bristles can specifically trigger sustained leg activity independently of higher-order centers as headless flies could sustain prolonged leg movement upon mechanosensory stimulation. Moreover, while this sensory-evoked movement lacks intra- and inter-leg coordination, it still preserved basic antagonistic muscle activity. These findings suggest a parallel mechanism to trigger fast movement upon sensory stimulation. In addition, it provides a new model for movement initiation and a point-of-entry to define pre-motor circuits.

neuroscience↗