Biology subjects

Hurtado, O.

Publications and source records attributed to Hurtado, O..

6 recordsLinked to original sources

bioRxiv2026

CB2 activation during epileptogenesis recruits immunomodulatory monocytes and mitigates cognitive, affective and seizure outcomes

Temporal lobe epilepsy (TLE) is frequently associated with severe cognitive impairment and psychiatric comorbidities that are highly disabling and not targeted by anti-seizure medications, highlighting the need for therapies that target epileptogenesis rather than merely suppress seizures. Despite strong evidence implicating neuroinflammation in this process, anti-inflammatory approaches have not yielded such therapies yet. Infiltrating peripheral monocytes are widely viewed as detrimental amplifiers of post-status epilepticus (SE) inflammation, although emerging data suggest context-dependent protective roles. The cannabinoid receptor type 2 (CB2), highly expressed in myeloid cells, represents a potential immunomodulatory target linking leukocyte recruitment and inflammatory polarization. Using a juvenile rat model of TLE, we characterized hippocampal neuroinflammation and CB2 expression during epileptogenesis and evaluated the effects of transient CB2 activation with the selective agonist GP1a. SE induced a rapid but transient inflammatory response and robust recruitment of peripheral monocytes that persisted as anti-inflammatory monocyte-derived macrophages. CB2 activation did not suppress early cytokine induction but selectively enhanced recruitment of anti-inflammatory monocytes and modestly increased anti-inflammatory signaling. Importantly, transient CB2 stimulation preserved synaptic plasticity, improved cognitive performance, reduced anxiety-like behavior, and delayed seizure onset. These findings identify CB2-dependent modulation of peripheral myeloid cells as a potential disease-modifying axis in TLE.

neuroscience↗

bioRxiv2025

Does Infarct Size Influence Gut Barrier Integrity and Bacterial Translocation after Experimental Stroke?

BackgroundIschemic stroke (IS) triggers brain injury and systemic changes, including gut dysbiosis, intestinal barrier dysfunction (IBD), and bacterial translocation (BT). Although larger infarcts are associated with higher infection risk, it is unclear whether lesion size directly influences gut barrier integrity or bacterial dissemination. MethodsMale C57BL/6 mice underwent permanent middle cerebral artery occlusion (MCAO) proximally or distally to generate large or small infarcts. Seventy-two hours post-ischemia, infarct volume was measured by MRI, and BT was assessed in mesenteric lymph nodes, liver, spleen, and lungs. ZO-1 and MMP9 expression were used to evaluate intestinal barrier integrity. Peripheral and central inflammation were assessed by flow cytometry and immunofluorescence. ResultsProximal MCAO produced larger infarcts than distal MCAO. The proportion of animals exhibiting BT was lower in distal MCAO, but this difference was not statistically significant. ZO-1 expression did not differ between groups, while MMP9 was increased only in animals with BT, independent of infarct size. BT was associated with more pronounced lymphopenia and enhanced microglial activation and T-cell infiltration in the brain. The composition of translocated bacteria was similar across groups. ConclusionsInfarct size alone does not determine IBD or BT, although BT is linked to intestinal and cerebral inflammation. This study evaluates for the first time the effect of lesion magnitude on IBD and BT, highlighting the complex interplay between cerebral injury and gut-systemic interactions.

neuroscience↗

bioRxiv2025

Sub-strain-Dependent Differences in Gut Barrier Permeability, Bacterial Translocation and Post-Stroke Inflammation in Wistar Rats

BackgroundStroke induces profound neuroinflammation and systemic immune dysregulation, including disturbances in gut homeostasis. Experimental evidence suggests that intestinal barrier permeability (IBP) and bacterial translocation (BT) critically influence stroke outcomes. However, biological variability among commonly used rodent sub-strains has received limited attention. MethodsIn this pilot study, we compared post-stroke immune responses in two Wistar rat sub-strains obtained from different suppliers: RccHan (Envigo) and RjHan (Janvier). Following transient middle cerebral artery occlusion, animals were assessed 72 hours later and stratified according to the presence or absence of BT. Immune cell populations in blood and bone marrow were analyzed by flow cytometry, and leukocyte infiltration into ischemic brain tissue was quantified by immunohistochemistry. ResultsBoth sub-strains developed significant infarcts and neurological deficits. RccHan rats displayed larger infarct volumes and more extensive BT across multiple organs. In contrast, RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but showed greater IBP. Although dissemination was broader in RccHan rats, overall bacterial burden was slightly lower compared with RjHan, and extra-intestinal bacterial composition differed between groups. Notably, RjHan rats presented stronger systemic and central immune activation, with marked alterations in lymphocyte and monocyte populations and enhanced granulocyte and T cell infiltration within ischemic lesions. ConclusionsThese findings demonstrate that sub-strain origin profoundly influences post-stroke intestinal barrier integrity, bacterial dissemination, and immune responses. Considering sub-strain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.

neuroscience↗

bioRxiv2023

Coordination of host and endosymbiont gene expression governs endosymbiont growth and elimination in the cereal weevil Sitophilus spp.

BackgroundInsects living in nutritionally poor environments often establish long-term relationships with intracellular bacteria that supplement their diets and improve their adaptive and invasive powers. Even though these symbiotic associations have been extensively studied on physiological, ecological and evolutionary levels, few studies have focused on the molecular dialogue between host and endosymbionts to identify genes and pathways involved in endosymbiosis control and dynamics throughout host development. ResultsWe simultaneously analyzed host and endosymbiont gene expression during the life cycle of the cereal weevil Sitophilus oryzae, from larval stages to adults, with a particular emphasis on emerging adults where the endosymbiont Sodalis pierantonius experiences a contrasted growth-climax-elimination dynamics. We unraveled a constant arms race in which different biological functions are intertwined and coregulated across both partners. These include immunity, metabolism, metal control, apoptosis, and bacterial stress response. ConclusionsThe study of these tightly regulated functions, which are at the center of symbiotic regulations, provides evidence on how hosts and bacteria finely tune their gene expression and respond to different physiological challenges constrained by insect development in a nutritionally limited ecological niche. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=143 HEIGHT=200 SRC="FIGDIR/small/535335v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@800121org.highwire.dtl.DTLVardef@1ca2c25org.highwire.dtl.DTLVardef@183d56org.highwire.dtl.DTLVardef@163074f_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2023

Transcriptomic-based selection of reference genes for quantitative real-time PCR in an insect endosymbiotic model

Reference genes are a fundamental tool for analyses of gene expression by real-time quantitative PCR (qRT-PCR), in that they ensure the correct comparison between conditions, stages, or treatments. Because of this, selection of appropriate genes to use as references is crucial for proper application of the technique. Nevertheless, efforts to find appropriate, stably expressed transcripts are still lacking, in particular in the field of insect science. Here, we took advantage of a massive transcriptomic high-throughput analysis of various developmental stages of the gut and associated-bacteriomes of the cereal weevil Sitophilus oryzae and identified a subset of stably expressed genes with the potential to be used as housekeeping genes from the larva to the adult stage. We employed several normalization techniques to select the most suitable genes among our subset. Our final selection includes three genes - TAO, YTH3 and PP12A - which can also be used to compare transcript abundance at various developmental stages in symbiotic insects, and in insects devoid of endosymbionts (aposymbiotic). Since they are well conserved, these genes have the potential to be useful for many other insect species. This work confirms the interest in using large-scale, unbiased methods for reference gene selection.

molecular biology↗

bioRxiv2022

IPSILESIONAL HIPPOCAMPAL GABA CORRELATES WITH COGNITIVE IMPAIRMENT AND MALADAPTIVE NEUROGENESIS AFTER STROKE IN MICE

BackgroundCognitive dysfunction is a frequent stroke sequela but its pathogenesis and treatment remain unresolved. Involvement of aberrant hippocampal neurogenesis and maladaptive circuitry remodelling has been proposed but their mechanisms are unknown. Our aim was to evaluate potential underlying molecular/cellular events implicated. MethodsStroke was induced by permanent occlusion of the middle cerebral artery (MCAO) in 2-month-old C57BL/6 male mice. Hippocampal metabolites/neurotransmitters were analysed longitudinally by in vivo magnetic resonance spectroscopy (MRS). Cognitive function was evaluated with the contextual fear conditioning test. Microglia, astrocytes, neuroblasts and interneurons were analysed by immunofluorescence. ResultsApproximately 50% of mice exhibited progressive post-MCAO cognitive impairment. Notably, immature hippocampal neurons in the impaired group displayed more severe aberrant phenotypes than those from the non-impaired group. Using MRS, significant bilateral changes in hippocampal metabolites such as myo-Inositol (mIns) or N-acetylaspartic acid (NAA) were found that correlated, respectively, with numbers of glia and immature neuroblasts in the ischemic group. Importantly, some metabolites were specifically altered in the ipsilateral hippocampus suggesting its involvement in aberrant neurogenesis and remodelling processes. Specifically, MCAO animals with higher hippocampal GABA levels displayed worse cognitive outcome. Implication of GABA in this setting was supported by the amelioration of ischemia-induced memory deficits and aberrant hippocampal neurogenesis after blocking pharmacologically GABAergic neurotransmission. These data suggest that GABA exerts its detrimental effect, at least partly, by affecting morphology and integration of newborn neurons into the hippocampal circuits. ConclusionsHippocampal GABAergic neurotransmission could be considered a novel diagnostic and therapeutic target for post-stroke cognitive impairment.

animal behavior and cognition↗