Pre- and Post-Synaptic protein in the major depressive Disorder: From neurobiology to therapeutic targets.

Major depressive disorder (MDD) has demonstrated its negative impact on various aspects of the lives of those affected. Although several therapies have been developed over the years, it remains a challenge for mental health professionals. Thus, understanding the pathophysiology of MDD is necessary to improve existing treatment options or seek new therapeutic alternatives. Clinical and preclinical studies in animal models of depression have shown the involvement of synaptic plasticity in both the development of MDD and the response to available drugs. However, synaptic plasticity involves a cascade of events, including the action of presynaptic proteins such as synaptophysin and synapsins and postsynaptic proteins such as postsynaptic density-95 (PSD-95). Additionally, several factors can negatively impact the process of spinogenesis/neurogenesis, which are related to many outcomes, including MDD. Thus, this narrative review aims to deepen the understanding of the involvement of synaptic formations and their components in the pathophysiology and treatment of MDD.

Deciphering the gut microbiota of zebrafish, the most used fish as a biological model: A meta-analytic approach.

A meta-analytic approach deciphered the taxonomic profile of the zebrafish gut microbiota at different developmental stages. Data (16S rDNA) were systematically searched in databases, selecting those with intestine samples of fish not exposed to a particular treatment or challenge (e.g., pathogens, dietetic tests, xenobiotics, etc.) and obtaining 340 samples to be processed. Results revealed marked differences between the developmental phases. Proteobacteria was the dominant phylum in the larval phase, with a relative abundance of 90%, while the rest of the phyla did not exceed 2%. Vibrio, Aeromonas, Plesiomonas, Pseudomonas, Shewanella, and Acinetobacter were the dominant genera in this phase. Transitional changes were observed after the larvae stage. Proteobacteria still registered high abundance (48%) in the juvenile phase, but Fusobacteria (40%) and Bacteriodota (5.9%) registered considerable increases. Genera, including Cetobacterium, Plesiomonas, Aeromonas, Vibrio, and Flavobacterium, dominated this stage. The phyla Proteobacteria (48%) and Fusobacteria (35%) were strongly established in the adult phase. Cetobacterium was registered as the most abundant genus, followed by Aeromonas, Acinetobacter, Plesiomonas, Vibrio, and ZOR0006 (Firmicutes; 6%). In conclusion, the composition of the intestinal microbiota of zebrafish is consistently determined by two primary phyla, Proteobacteria and Fusobacteria; however, this composition varies depending on the developmental stage. Cetobacterium and Aeromonas are the most relevant genera in juveniles and adults. Finally, these results reveal a consistent pattern of certain bacterial groups in the zebrafish microbiota that could help shape gnotobiotic models (colonized with a specific known bacterial community) or synthetic microbiota (in vitro assembly of microbes), among other approaches.

Apical periodontitis as an aggravating factor for the severity of rheumatoid arthritis: An animal study.

AIM: The present study investigated the influence of apical periodontitis (AP) on the severity of rheumatoid arthritis (RA) using a Wistar rat model. METHODOLOGY: Forty male Wistar rats were distributed across four groups (n = 10) based on the induction of RA and AP: Control, RA, AP, and RA + AP. RA was induced through two immunisations with type II collagen emulsified in incomplete Freund's adjuvant, followed by one immunisation with complete Freund's adjuvant. After 21 days of RA induction, AP was induced by exposing the pulp of four molars. Animals were euthanized after 28 days of pulp exposure. Through the experiment, visual and behavioural assessments tracked RA development and the knees and hind paw joints were measured. Micro-computed tomography scans of knees and hind paws, as well as mandibles and maxillae, were conducted to evaluate RA severity and the presence of AP, respectively. Serum samples were collected to analyse proinflammatory cytokines (IL-1ß, IL-2, IL-17, and TNF-α). Non-parametric data were analysed using the Kruskal-Wallis test followed by Student-Newman-Keuls test, while one-way anova followed by Tukey's test was performed for parametric data. A significance level of 5% was employed. RESULTS: All molars submitted to access cavity developed AP. All joints subjected to arthritis induction developed the disease, with AP + RA demonstrating a higher arthritis severity when compared to the RA group (p < .05). RA + AP group displayed a significantly larger hind paw and knee circumference compared to the RA group (p < .05). Micro-CT images of RA and RA + AP groups revealed joints with erosions and bone deformities, with a significantly lower bone surface density, lower trabecular number and higher trabecular separation in the hind paw and a significantly lower percent bone volume and higher trabecular separation in the knees of RA + AP group compared to RA group (p < .05). RA + AP group exhibited a significantly higher level of TNF-α and a lower level of IL-2 compared to all other groups (p < .05). Both RA and RA + AP groups had significantly higher IL-17 levels (p < .05), while there was no significant difference in IL-1ß levels among the groups (p > .05). CONCLUSION: The findings from this study underscore a possible relationship between apical periodontitis and the exacerbation of rheumatoid arthritis.

Jaboticaba Peel Extract Attenuates Ovariectomy-Induced Bone Loss by Preserving Osteoblast Activity.

Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Since jaboticaba peel extract (JPE) added to the culture medium enhanced the osteogenic potential of mesenchymal stem cells (MSCs) derived from osteoporotic rats, we hypothesized that JPE prevents the development of ovariectomy-induced osteoporosis. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy. Then, the femurs were subjected to microcomputed tomography and histological analyses, and the osteoblast and adipocyte differentiation of MSCs was evaluated. JPE attenuated ovariectomy-induced bone loss, as evidenced by higher bone volume/total volume and trabecular number, along with lower trabecular separation and bone marrow adiposity. These protective effects of JPE on bone tissue are due to its ability to prevent the imbalance between osteoblast and adipocyte differentiation of MSCs, since, compared with MSCs derived from ovariectomized rats treated with vehicle, MSCs treated with JPE exhibited higher gene and protein expression of osteogenic markers and extracellular matrix mineralization, as well as lower gene expression of adipogenic markers. These data highlight the potential therapeutic use of JPE to prevent osteoporosis.

Partners in health and disease: pineal gland and purinergic signalling.

In mammal's pineal glands, ATP interacts with the high-affinity P2Y1 and the low-affinity P2X7 receptors. ATP released from sympathetic nerve terminals potentiates noradrenaline-induced serotonin N-acetyltransferase (Snat) transcription, N-acetylserotonin (NAS), and melatonin (MLT) synthesis. Circulating melatonin impairs the expression of adhesion molecules in endothelial cells, blocking the migration of leukocytes. Acute defence response induced by pathogen- and danger/damage-associated molecular patterns (PAMPs and DAMPs) triggers the NF-κB pathway in pinealocytes and blocks the transcription of Snat. Therefore, the darkness hormone is not released, and neutrophils and monocytes migrate to the lesion sites. ATP released in high amounts from apoptotic and death cells was considered a DAMP, and the blockage of P2X7 receptors was tested as a new class of drugs for treating brain damage. However, this is not a simple equation. High ATP injected in a lateral ventricle blocked MLT, but not NAS, synthesis as it impairs the transcription of acetyl serotonin N-methyltransferase. NAS is released in the plasma and the cerebral spinal fluid. NAS also blocks the rolling and adhesion of leukocytes to endothelial cells. Otherwise, it is metabolised specifically in each brain area to provide the requested concentration of MLT as a neuroprotector. As observed in physiological conditions, high extracellular ATP, different from the other DAMPs, reports the environmental light/dark cycle rhythm because NAS substitutes MLT as the nocturnal chemical indicator, the darkness hormone. Thus, blocking the P2X7R should not be considered a universal therapy for improving acute strokes, as MLT and ATP are partners in health and disease.

Embryotoxicity and teratogenesis of orthodontic acrylic resin in zebrafish.

Objectives: This study investigated the in vivo embryotoxicity, teratogenic potential, and additional effects of orthodontic acrylic resin as well as its components, utilizing zebrafish as a model organism. The research focused on morphological, cardiac, behavioral, and cognitive evaluations that were performed on embryos and larval-stage animals subjected to chronic exposure. Materials and methods: Embryo and larval-stage zebrafish were categorized into five experimental groups, which were further subdivided into five subgroups. These subgroups included three specific doses for each tested substance, a control with the vehicle (0.1 % dimethyl sulfoxide in water), and an absolute control (water). Assessments were performed on day 5 post-fertilization, which included morphological, cardiac, behavioral, and cognitive evaluations. All experiments had a sample size of ten animals and were performed in triplicate. Survival and hatching rates were analyzed using the Kaplan-Meier test, while other measurements were assessed using one-way analysis of variance (ANOVA), followed by the Tukey post hoc test. Results: Statistically significant differences were observed between the control and treatment groups across all the tested substances for heart rate, cognitive responsiveness, and cellular apoptosis. However, survival, hatching rate, and other parameters exhibited no significant variation, except for the highest dose in the dibutyl phthalate group, which demonstrated a notable difference in survival. Conclusions: Chronic exposure to acrylic resin and its components may be associated with decreased cognitive ability and cardiac rhythm, as well as an increase in the level of cellular apoptosis in zebrafish.

Systemic administration of propranolol reduces bone resorption and inflammation in apical periodontitis of chronically stressed rats.

AIM: To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats. METHODOLOGY: Twenty-four 70-day-old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP-Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT-PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one-way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal-Wallis followed by Dunn's test. Significance level was set at 5% (p < .05) for all assessed parameters. RESULTS: Micro-CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p < .05), but no differences were observed between the Control and AP + S + PRO groups (p > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p < .05). CONCLUSIONS: Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti-inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms.

Redefining the Role of Ornithine Aspartate and Vitamin E in Metabolic-Dysfunction-Associated Steatotic Liver Disease through Its Biochemical Properties.

It is known that the inflammation process leading to oxidative stress and thyroid hormone metabolism dysfunction is highly altered in metabolic dysfunction associated with steatotic liver disease (MASLD). This study aims to address the effect of ornithine aspartate (LOLA) and vitamin E (VitE) in improving these processes. Adult Sprague-Dawley rats were assigned to five groups and treated for 28 weeks: controls (n = 10) received a standard diet (for 28 weeks) plus gavage with distilled water (DW) from weeks 16 to 28. MASLD groups received a high-fat and choline-deficient diet for 28 weeks (MASLD group) and daily gavage with 200 mg/kg/day of LOLA, or twice a week with 150 mg of VitE from weeks 16-28. LOLA diminished collagen deposition (p = 0.006). The same treatment diminished carbonyl, TBARS, and sulfhydryl levels and GPx activity (p < 0.001). Type 3 deiodinase increased in the MASLD group, downregulating T3-controlled genes, which was corrected in the presence of LOLA. LOLA also promoted a near-normalization of complex II, SDH, and GDH activities (p < 0.001) and improved reticulum stress, with a reduction in GRP78 and HSPA9/GRP75 protein levels (p < 0.05). The enhanced energy production and metabolism of thyroid hormones, probably because of GSH replenishment provided by the L-glutamate portion of LOLA, opens a new therapeutic approach for MASLD.

A new standardization for the use of chicken embryo: selection of target from the phage display library and infection.

The filamentous bacteriophage M13KO7 (M13) is the most used in phage display (PD) technology and, like other phages, has been applied in several areas of medicine, agriculture, and in the food industry. One of the advantages is that they can modulate the immune response in the presence of pathogenic microorganisms, such as bacteria and viruses. This study evaluated the use of phage M13 in the chicken embryos model. We inoculated 13-day-old chicken embryos with Salmonella Pullorum (SP) and then evaluated survival for the presence of phage M13 or E. coli ER2738 (ECR) infected with M13. We found that the ECR bacterium inhibits SP multiplication in 0.32 (M13-infected ECR) or 0.44 log UFC/mL (M13-uninfected ECR) and that the ECR-free phage M13 from the PD library can be used in chicken embryo models. This work provides the use of the chicken embryo as a model to study systemic infection and can be employed as an analysis tool for various peptides that M13 can express from PD selection. KEY POINTS: • SP-infected chicken embryo can be a helpful model of systemic infection for different tests. • Phage M13 does not lead to embryonic mortality or cause serious injury to embryos. • Phage M13 from the PD library can be used in chicken embryo model tests.

Long-term Environmental Enrichment Normalizes Schizophrenia-like Abnormalities and Promotes Hippocampal Slc6a4 Promoter Demethylation in Mice Submitted to a Two-hit Model.

Here, we explored the impact of prolonged environmental enrichment (EE) on behavioral, neurochemical, and epigenetic changes in the serotonin transporter gene in mice subjected to a two-hit schizophrenia model. The methodology involved administering the viral mimetic PolyI:C to neonatal Swiss mice as a first hit during postnatal days (PND) 5-7, or a sterile saline solution as a control. At PND21, mice were randomly assigned either to standard environment (SE) or EE housing conditions. Between PND35-44, the PolyI:C-treated group was submitted to various unpredictable stressors, constituting the second hit. Behavioral assessments were conducted on PND70, immediately after the final EE exposure. Following the completion of behavioral assessments, we evaluated the expression of proteins in the hippocampus that are indicative of microglial activation, such as Iba-1, as well as related to neurogenesis, including doublecortin (Dcx). We also performed methylation analysis on the serotonin transporter gene (Slc6a4) to investigate alterations in serotonin signaling. The findings revealed that EE for 50 days mitigated sensorimotor gating deficits and working memory impairments in two-hit mice and enhanced their locomotor and exploratory behaviors. EE also normalized the overexpression of hippocampal Iba-1 and increased the expression of hippocampal Dcx. Additionally, we observed hippocampal demethylation of the Slc6a4 gene in the EE-exposed two-hit group, indicating epigenetic reprogramming. These results contribute to the growing body of evidence supporting the protective effects of long-term EE in counteracting behavioral disruptions caused by the two-hit schizophrenia model, pointing to enhanced neurogenesis, diminished microglial activation, and epigenetic modifications of serotonergic pathways as underlying mechanisms.

Therapeutic Effect of Alpha Lipoic Acid in a Rat Preclinical Model of Preeclampsia: Focus on Maternal Signs, Fetal Growth and Placental Function.

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females (n = 19-16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE.

Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections.

Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.

An exploratory study on the ability of manganese to supplement rotenone neurotoxicity in rats.

Parkinson's disease (PD) is a complex disorder, primarily of idiopathic origin, with environmental stressors like rotenone and manganese linked to its development. This study explores their potential interaction and resulting neurotoxicity, aiming to understand how environmental factors contribute to PD. In an eight-day experiment, male Wistar rats weighing 280-300 g were subjected to rotenone, manganese, or a combination of both. Various parameters were assessed, including body weight, behavior, serum markers, tissue damage, protein levels (tyrosine hydroxylase, Dopamine- and cAMP-regulated neuronal phosphoprotein -DARPP-32-, and α-synuclein), and mitochondrial function. Manganese heightened rotenone's impact on reducing food intake without causing kidney or liver dysfunction. However, the combined exposure intensified neurotoxicity, which was evident in augmented broken nuclei and decreased tyrosine hydroxylase and DARPP-32 levels in the striatum. While overall mitochondrial function was preserved, co-administration reduced complex IV activity in the midbrain and liver. In conclusion, our findings revealed a parallel toxic effect induced by rotenone and manganese. Notably, while these substances do not target the same dopaminergic regions, a notable escalation in toxicity is evident in the striatum, the brain region where their toxic effects converge. This study highlights the need for further exploration regarding the interaction of environmental factors and their possible impact on the etiology of PD.

Effects of gallic acid and physical training on liver damage, force, and anxiety in obese mice: Hepatic modulation of Sestrin 2 (SESN2) and PGC-α expression.

Obesity and overweight are multifactorial diseases affecting more than one-third of the world's population. Physical inactivity contributes to a positive energy balance and the onset of obesity. Exercise combined with a balanced diet is an effective non-pharmacological strategy to improve obesity-related disorders. Gallic acid (GA), is a natural endogenous polyphenol found in a variety of fruits, vegetables, and wines, with beneficial effects on energetic homeostasis. The present study aims to investigate the effects of exercise training on obese mice supplemented with GA. Animal experimentation was performed with male Swiss mice divided into five groups: ST (standard control), HFD (obese control), HFD + GA (GA supplement), HFD + Trained (training), and HFD + GA + Trained (GA and training). The groups are treated for eight weeks with 200 mg/kg/body weight of the feed compound and, if applicable, physical training. The main findings of the present study show that GA supplementation improves liver fat, body weight, adiposity, and plasma insulin levels. In addition, animals treated with the GA and a physical training program demonstrate reduced levels of anxiety. Gene expression analyses show that Sesn2 is activated via PGC-1α independent of the GATOR2 protein, which is activated by GA in the context of physical activity. These data are corroborated by molecular docking analysis, demonstrating the interaction of GA with GATOR2. The present study contributes to understanding the metabolic effects of GA and physical training and demonstrates a new hepatic mechanism of action via Sestrin 2 and PGC-1α.

Increased Depressive-like, Anxiety-like, and Perseverative-like Behavior in Binge Eating Model in Juvenile Rats.

The aim of the present study was to evaluate depressive-like, anxiety-like, and perseverative-like behaviors in a binge eating model. Juvenile Wistar rats, using the binge eating model, were compared to caloric restriction, induced stress, and control groups. Rats of the induced stress group presented binge-like behaviors in standard food intake in the second cycle of the experiment when compared to the caloric restriction group and the binge eating model group. Depressive-like behavior was observed in the binge eating model group with longer immobility time (p < 0.001) and less swim time (p < 0.001) in comparison to the control group. Anxiety-like behavior was observed by shorter duration of burying latency in the binge eating model group when compared to the induced stress group (p = 0.04) and a longer duration of burying time when compared to the control group (p = 0.02). We observed perseverative-like behavior by the binge model group, who made more entries to the new arm (p = 0.0004) and spent a longer time in the new arm when compared to the control group (p = 0.0001). Our results show differences in behaviors between the groups of rats studied. These results suggest that calorie restriction-refeeding, along with stress, may lead to depressive-like, anxiety-like, and perseverative-like behavioral changes in male Wistar rats.

Histopathological Analysis of Brains from Dogs Infected with Canine Distemper Virus.

We describe the use of conventional histology and immunohistochemistry against canine distemper virus (CDV) to examine the brains of domestic dogs with a confirmed diagnosis of CDV infection. Histologically, to identify the main typical lesions, we used conventional H&E stain; to evaluate the progressive demyelination, we used Luxol Fast Blue stain; and to identify the presence of viral particles in these affected regions, we used immunohistochemistry against CDV. We confirm that the histopathological analysis of brains of distemper-infected dogs is a powerful tool to evaluate the typical brain lesions and could be used as an interesting natural model to continue studying the pathogenesis of canine distemper in different species and/or other morbillivirus infections, like measles.

Body composition and metabolic consequences of antibiotics most frequently administered to newborns in intensive care units: an experimental study in healthy newborn rats.

Introduction: The increasing overuse of antibiotics in recent years has led to antibiotics being the most prescribed drugs for pediatric patients, and 72% of patients in the neonatal intensive care unit are treated with antibiotics. One effect of antibiotic use is the alteration of the microbiota, which is associated with metabolic disorders, including obesity. Methods: This experimental study in newborn rats compared the administration of ampicillin/meropenem (Access/Watch groups) at 100/10 µg/g every 12 h, cefotaxime 200 µg/g every 24 h (Watch group), and amikacin 15 µg/g every 24 h (Access group) versus saline solution as the control. Each antibiotic was adjusted to the required dosages based on weight, and the doses were administered intraperitoneally daily for 5 days to 10-14 newborn male rats per group. A comparison of the morphometric and biochemical parameters registered on day 28 was performed using ANOVA. Results: Amikacin had the largest effect on morphometric measurements, and low-density lipoprotein cholesterol, while cefotaxime had the largest effect on glucose and triglycerides, whereas ampicillin/meropenem produced the weakest effect on the measured parameters. Discussion: The administration of antibiotics in the neonatal stage can affect the body composition of rats as well as the lipid and carbohydrate serum levels. Future studies should evaluate the toxicity of antibiotics in immature neonatal organs and could help to improve therapeutic decisions and prevent the unjustified use of antibiotics in newborns, thereby reducing metabolic consequences.

CD8 T cells are dispensable for experimental autoimmune prostatitis induction and chronic pelvic pain development.

Introduction: Chronic Pelvic Pain Syndrome or Chronic Prostatitis (CPPS/CP) is the most prevalent urologic affliction among young adult men. It is a challenging condition to treat, which significantly decreases patient quality of life, mostly because of its still uncertain aetiology. In that regard, an autoimmune origin is a prominent supported theory. Indeed, studies in patients and in rodent models of Experimental Autoimmune Prostatitis (EAP) have provided compelling evidence suggesting a key role of CD4 Th1 cells in disease pathogenesis. However, the implication of other prominent effectors of the immune system, such as CD8 T cells, has yet to be studied. Methods: We herein analyzed the induction of prostatitis and the development of chronic pelvic pain in EAP using CD8 T cell-deficient animals. Results: We found similarly elevated PA-specific immune responses, with high frequencies of specific IFNg+CD4+ and IL17+CD4+ T cells in prostate draining lymph nodes from PA-immunized either CD8 KO or wild type animals with respect to controls. Moreover, these peripheral immune responses were paralleled by the development of significant chronic pelvic pain, and accompanied by prostate histological lesions, characterized by hemorrhage, epithelial cell desquamation, marked periglandular leukocyte infiltration, and increased collagen deposition in both, PA-immunized CD8 KO and wild type animals. As expected, control animals did not develop prostate histological lesions. Discussion: Our results indicate that CD8 T cells do not play a major role in EAP pathogenesis and chronic pelvic pain development. Moreover, our results corroborate the previous notion that a CD4 Th1 associated immune response drives the induction of prostate tissue inflammation and the development of chronic pelvic pain.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease.

BACKGROUND: Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy. AIM: To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD. METHODS: Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16th week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system. RESULTS: Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species Helicobacter rodentium, Parabacteroides goldsteinii, and Parabacteroides distasonis. The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis. CONCLUSION: Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.