Biology subjects

Petrella, L.

Publications and source records attributed to Petrella, L..

5 recordsLinked to original sources

bioRxiv2025

An in vitro platform for characterizing axonal electrophysiology of individual human iPSC-derived nociceptors

Current treatments against severe forms of neuropathic pain demonstrate insufficient efficacy or lead to unwanted side effects as they fail to specifically target the affected nociceptors - a specialized subclass of sensory neurons conveying potentially damaging stimuli information to the central nervous system. Neuropathic pain may involve different nociceptor subtypes in different patients. Tools that can distinguish nociceptive axons would enable a more targeted compound screening. Therefore, we developed an in vitro platform combining a CMOS-based high-density microelectrode array with a polydimethylsiloxane (PDMS) guiding microstructure that captures the electrophysiological responses of nociceptors. Human induced pluripotent stem cell-derived (iPSC) nociceptors were cultured at low density with axons distributed through parallel 4 x 10 {micro}m microchannels exiting the seeding well before converging to a bigger axon-collecting channel. This configuration allowed the measurement of stimulation-induced responses of individual axons. Nociceptors were found to exhibit a great diversity of electrophysiological response profiles that can be classified into different functional archetypes. Moreover, we show that some responses are affected by applying the TRPV1 agonist capsaicin. Overall, results using our platform demonstrate that we were able to distinguish nociceptive axons from different subtypes. The platform provides a promising tool for screening potential candidates for nociceptor-specific drugs.

bioengineering↗

bioRxiv2022

Pilot MRI study of carbon monoxide (CO) against ischemic stroke in mice: blood brain barrier integrity and metabolic pattern

Although stroke is the main cause of brain damage worldwide, stroke therapies are based on blood reperfusion and do not target cerebral parenchyma. Ischemic stroke (representing 87% of all strokes) causes cerebral damage due to oxygen and tissue energy depletion, which lead to acidosis, inflammation, excitotoxicity and oxidative stress. Carbon monoxide (CO) is an endogenous gasotransmitter produced by heme oxygenase cleavage of the heme group. CO promotes cytoprotection by limiting inflammation and preventing cell death in several tissues including the brain. Previous studies have demonstrated the protective role of CO in the mouse ischemic stroke model, middle cerebral artery occlusion (MCAo) by histological analysis when CO is when applied before ischemia. Herein, there are two main novelties. First CO is administrated following stroke, which better mimics its potential future use as therapeutic drug. Secondly, imaging techniques were used to elucidate the effect of this gasotransmitter at the metabolic, vascular and anatomic levels. The putative neuroprotective effects of CO following MCAo were assessed by 3 i.p. injections of the CO-releasing molecule CORM-A1 (3 mg/kg), administered 6, 24 and 48h after reperfusion. Magnetic Resonance Imaging was performed 1 day and 7 days after reperfusion using T2-weighted, diffusion weighted images, proton spectroscopy (1H-MRS) and perfusion (dynamic contrast enhanced images). 1H-MRS also allowed the comparison between metabolite signatures at day 1 versus 7 day following MCAo. Furthermore, CORM-A1 limited the loss of blood-brain barrier (BBB) integrity as it reduced the edema formation. Furthermore, the CO donor minimized the metabolite load loss at an early stage after MCAo, both in striatum and cortex. In conclusion and based on MRI analysis, CO has a protective role in the recovery from stroke injury, mainly by acting on BBB integrity and brain metabolism.

neuroscience↗

bioRxiv2022

Temperature Stressed Caenorhabditis elegans Males Prioritize Feeding over Mating Resulting in Sterility

Heat stress negatively impacts fertility in sexually reproducing organisms at sublethal temperatures. These temperature stress effects are typically more pronounced in males. In some species, sperm production, quality, and motility are the primary cause of male infertility under temperature stress. However, this is not the case in the model nematode Caenorhabditis elegans where changes in mating behavior are the primary cause of fertility loss. We report that temperature stressed C. elegans males experience a dramatic upset in the balance of their food drive and their mating drive such that they prioritize feeding over mating. This change in priorities is due partially to increased expression of the chemoreceptor odr-10 in the AWA sensory neurons. Increased odr-10 expression in the presence of ample food demonstrates that males are unable to experience satiety, thus they never leave a food source and engage in mate searching behavior. These results demonstrate that moderate temperature stress may have profound and previously underappreciated effects on reproductive behaviors. As climate change associated temperature variability becomes more commonplace, it will be imperative to understand how temperature stress affects conserved behavioral elements critical to reproduction.

animal behavior and cognition↗

bioRxiv2019

C. elegans synMuv B proteins regulate spatial and temporal chromatin compaction during development

Tissue-specific establishment of repressive chromatin through creation of compact chromatin domains during development is necessary to ensure proper gene expression and cell fate. C. elegans synMuv B proteins are important for the soma/germline fate decision and mutants demonstrate ectopic germline gene expression in somatic tissue, especially at high temperature. We show that C. elegans synMuv B proteins regulate developmental chromatin compaction and that timing of chromatin compaction is temperature sensitive in both wild-type and synMuv B mutants. Chromatin compaction in mutants is delayed into developmental time-periods when zygotic gene expression is upregulated and demonstrates an anterior-to-posterior pattern. Loss of this patterned compaction coincides with the developmental time-period of ectopic germline gene expression that leads to a developmental arrest in synMuv B mutants. Thus, chromatin organization throughout development is regulated both spatially and temporally by synMuv B proteins to establish repressive chromatin in a tissue-specific manner to ensure proper gene expression.

developmental biology↗

bioRxiv2018

LIN-15B promotes enrichment of H3K9me2 on the promoters of a subset of germline genes that are repressed in somatic cells in C. elegans

Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three Caenorhabditis elegans synMuv B mutants, lin-15B, lin-35, and lin-37, all of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. LIN-15B has been proposed to work with the DREAM complex but has not been shown biochemically to be a complex member. We found that in wild-type worms synMuv B target genes and germline genes are enriched for the repressive histone modification dimethylation of histone H3 on lysine 9 (H3K9me2) at their promoters. Genes with H3K9me2 promoter localization are distributed across the autosomes and not biased toward autosomal arms like broad H3K9me2 domains. Both synMuv B targets and germline genes display dramatic reduction of H3K9me2 promoter localization in lin-15B mutants, but much weaker reduction in lin-35 and lin-37 mutants. This is the first major difference reported between lin-15B and DREAM complex mutants, which likely represents a difference in molecular function for these synMuv B proteins. In support of the pivotal role of H3K9me2 in regulation of germline genes through LIN-15B, global loss of H3K9me2 but not H3K9me3 results in phenotypes similar to synMuv B mutants, high temperature larval arrest and ectopic expression of germline genes in the soma. We propose that LIN-15B-driven enrichment of H3K9me2 on promoters of germline genes contributes to repression of those genes in somatic tissues.

genetics↗