Sex-dependent circadian alterations of both central and peripheral clock genes expression and gut-microbiota composition during activity-based anorexia in mice.

Rationale: Patients with anorexia nervosa (AN) often present sleep disorders and circadian hormonal dysregulation. The role of the microbiota-gut-brain axis in the regulation of feeding behavior has emerged during the last decades but its relationships with the circadian rhythm remains poorly documented. Thus, we aimed to characterize the circadian clock genes expression in peripheral and central tissues in the activity-based anorexia mouse model (ABA), as well as the dynamics of the gut-microbiota composition.

Neuroprotective and Anti-inflammatory Effects of Rubiscolin-6 Analogs with Proline Surrogates in Position 2.

Naturally occurring peptides, such as rubiscolins derived from spinach leaves, have been shown to possess some interesting activities. They exerted central effects, such as antinociception, memory consolidation and anxiolytic-like activity. The fact that rubiscolins are potent even when given orally makes them very promising drug candidates.

Immunoglobulin G is a natural oxytocin carrier which modulates oxytocin receptor signaling: relevance to aggressive behavior in humans.

Oxytocin is a neuropeptide produced mainly in the hypothalamus and secreted in the CNS and blood. In the brain, it plays a major role in promoting social interactions. Here we show that in human plasma about 60% of oxytocin is naturally bound to IgG which modulates oxytocin receptor signaling.

Lactobacillus salivarius and Lactobacillus gasseri supplementation reduces stress-induced sugar craving in mice.

Objective: Increased intake of sweets or sugar craving may occur in response to chronic stress representing a risk factor for development of eating disorders and obesity. However, no safe treatment of stress-induced sugar craving is available. In this study we analysed effects of two Lactobacillus strains on food and sucrose intake in mice before and during their exposure to a chronic mild stress (CMS).

Bladder-colon chronic cross-sensitization involves neuro-glial pathways in male mice.

Background: Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity. Since pelvic organs share common sensory pathways, it is likely that those syndromes involve a cross-sensitization of the bladder and the colon. The precise pathophysiology remains poorly understood.

CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury.

Introduction: Although the physiological role of the C-terminal hydrolase domain of the soluble epoxide hydrolase (sEH-H) is well investigated, the function of its N-terminal phosphatase activity (sEH-P) remains unknown.

Objectives: This study aimed to assess in vivo the physiological role of sEH-P.

Methods: CRISPR/Cas9 was used to generate a novel knock-in (KI) rat line lacking the sEH-P activity.

Acute but Not Chronic Central Administration of the Neuropeptide 26RFa (QRFP) Improves Glucose Homeostasis in Obese/Diabetic Mice.

Introduction: The aim of the study is to investigate whether acute or chronic central administration of the hypothalamic neuropeptide 26RFa may ameliorate the glycemic control of obese/diabetic mice.

Methods: Mice were treated for 4 months with a high-fat (HF) diet and received a single i.c.

Effects of Bacterial CLPB Protein Fragments on Food Intake and PYY Secretion.

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of wild type (WT) or ΔClpB. However, until now, no study has shown its direct effect on food intake.

Gut microbiota depletion affects nutritional and behavioral responses to activity-based anorexia model in a sex-dependent manner.

Background & Aims: In the last decade, the role of the microbiota-gut-brain axis in eating behavior and anxiety-depressive disorders has gained increasing attention. Although a gut microbiota dysbiosis has been reported in anorectic patients, its pathophysiological role remains poorly understood. Thus, we aimed to characterize the potential role of gut microbiota by evaluating the effects of its depletion in the Activity-Based Anorexia (ABA) mouse model both in male and female mice.

Mineralocorticoid receptor blockade with finerenone improves heart function and exercise capacity in ovariectomized mice.

Aims: In post-menopausal women, incidence of heart failure with preserved ejection fraction is higher than in men. Hormonal replacement therapies did not demonstrate benefits. We tested whether the non-steroidal mineralocorticoid receptor antagonist finerenone limits the progression of heart failure in ovariectomized (OVX) mice with metabolic disorders.

Cell-penetrating, antioxidant SELENOT mimetic protects dopaminergic neurons and ameliorates motor dysfunction in Parkinson's disease animal models.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction for which there is an unmet need for better treatment options. Although oxidative stress is a common feature of neurodegenerative diseases, notably PD, there is currently no efficient therapeutic strategy able to tackle this multi-target pathophysiological process. Based on our previous observations of the potent antioxidant and neuroprotective activity of SELENOT, a vital thioredoxin-like selenoprotein, we designed the small peptide PSELT from its redox active site to evaluate its antioxidant properties in vivo, and its potential polyfunctional activity in PD models.

Coronaridine congeners potentiate GABA receptors and induce sedative activity in mice in a benzodiazepine-insensitive manner.

To determine whether (+)-catharanthine induces sedative- or anxiolytic/anxiogenic-like activity in male mice, proper animal paradigms were used. The results showed that (+)-catharanthine induces sedative-like activity in the 63-72 mg/Kg dose range in a flumazenil-insensitive manner, but neither this effect nor anxiolytic/anxiogenic-like activity was observed at lower doses. To determine the underlying molecular mechanism of the sedative-like activity, electrophysiological and radioligand binding experiments were performed with (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC] on GABA (GABARs) and glycine receptors (GlyRs).

Glucose homeostasis is impaired in mice deficient in the neuropeptide 26RFa (QRFP).

Introduction: 26RFa (pyroglutamyl RFamide peptide (QRFP)) is a biologically active peptide that has been found to control feeding behavior by stimulating food intake, and to regulate glucose homeostasis by acting as an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene knockout on the regulation of energy and glucose metabolism.

Research Design And Methods: 26RFa mutant mice were generated by homologous recombination, in which the entire coding region of prepro26RFa was replaced by the iCre sequence.

Intestinal lymphatic alteration in mouse models of energy imbalance.

In obesity or anorexia, changes in body composition and mostly alterations in fat mass distribution are observed. The lymphatic system, which is implicated in fat absorption, might play a major role in the phenotype and development of these pathologies. In this study, two mice animal models were used: the high-fat diet model used for obesity and the activity-based anorexia model for anorexia.

Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice-a new potential probiotic for appetite and body weight management.

Background/objectives: Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity.

Methods: The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.

HA4597 Strain Reduces Food Intake and Body Weight Gain and Improves Body Composition, Glucose, and Lipid Metabolism in a Mouse Model of Hyperphagic Obesity.

Use of new generation probiotics may become an integral part of the prevention and treatment strategies of obesity. The aim of the present study was to test the efficacy of a potential probiotic strain of lactic bacteria ( ) HA4597™, in a mouse model of obesity characterized by both hyperphagia and diet-induced adiposity. For this purpose, 10-week-old high-fat-diet (HFD)-fed hyperphagic / male mice received a daily treatment with 1.

Proteome modifications of gut microbiota in mice with activity-based anorexia and starvation: Role in ATP production.

Objective: Activity-based anorexia (ABA) in rodents is a behavioral model of anorexia nervosa, characterized by negative energy balance, hyperactivity, and dysbiosis of gut microbiota. Gut bacteria are known to produce energy substrates including adenosine triphosphate (ATP) and acetate. The aim of this study was to determine whether ABA alters the proteome of gut microbiota relevant to ATP and acetate production.

PT-31, a putative α2-adrenoceptor agonist, is effective in schizophrenia cognitive symptoms in mice.

Evidence of changes in central noradrenergic activity has been reported in schizophrenic patients and studies indicate that activation of the α2-adrenoceptor improves memory and neuroprotection. In this study, a new imidazolidine derivative 3-(2-chloro-6-fluorobenzyl)-imidazolidine-2,4-dione, PT-31, a putative α2A-adrenoceptor agonist, was evaluated in mouse models predictive of efficacy in the treatment of positive and cognitive symptoms of schizophrenia, as well as its ability to promote cerebellar granule cell survival in vitro, in the presence or absence of glutamate (100 µmol/l). PT-31 prevented apomorphine-induced climbing and the ketamine-induced hyperlocomotion, without inducing catalepsy or motor impairment.

Beneficial Effects of Remifentanil Against Excitotoxic Brain Damage in Newborn Mice.

Remifentanil, a synthetic opioid used for analgesia during cesarean sections, has been shown in experiments to exert anti-apoptotic activity on immature mice brains. The present study aimed to characterize the impact of remifentanil on brain lesions using an model of excitotoxic neonatal brain injury. Postnatal day 2 (P2) mice received three intraperitoneal injections of remifentanil (500 ng/g over a 10-min period) or saline just before an intracortical injection of ibotenate (10 μg).

Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase.

Inflammatory bowel diseases (IBD) are characterized by repetition of flares and remission periods leading to chronic postinflammatory sequelae. Among postinflammatory sequelae, one-third of patients with IBD are suffering from functional symptoms or psychological comorbidities that persist during remission. The aim of our study was to assess functional and behavioral sequelae of chronic colitis in rats with quiescent intestinal inflammation.

Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans.

Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11-24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1-13).

Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein Synthesis but Activated Autophagy during Anorexia-Induced Malnutrition in Mice.

Anorexia nervosa is an eating disorder often associated with intestinal disorders. To explore the underlying mechanisms of these disorders, the colonic proteome was evaluated during activity-based anorexia. Female C57Bl/6 mice were randomized into three groups: Control, Limited Food Access (LFA) and Activity-Based Anorexia (ABA).

Alterations of proteome, mitochondrial dynamic and autophagy in the hypothalamus during activity-based anorexia.

Restrictive anorexia nervosa is associated with reduced eating and severe body weight loss leading to a cachectic state. Hypothalamus plays a major role in the regulation of food intake and energy homeostasis. In the present study, alterations of hypothalamic proteome and particularly of proteins involved in energy and mitochondrial metabolism have been observed in female activity-based anorexia (ABA) mice that exhibited a reduced food intake and a severe weight loss.

Neuroprotective effects of the gliopeptide ODN in an in vivo model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopamine (DA) neurons through apoptotic, inflammatory and oxidative stress mechanisms. The octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which protects neurons against oxidative cell damages and apoptosis in an in vitro model of PD. The present study reveals that a single intracerebroventricular injection of 10 ng ODN 1 h after the last administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prevented the degeneration of DA neurons induced by the toxin in the substantia nigra pars compacta of mice, 7 days after treatment.