Bruno P Guiard

Paul Sabatier University - Toulouse III | UPS Toulouse · Centre de Recherches sur la Cognition Animale - UMR 5169 - CRCA

Achieving healthy aging is a global challenge requiring a deeper understanding of aging mechanisms, spanning from robustness to frailty. Although age-related alteration of the gut microbiome (microb-aging) is well studied, there is a lack of research investigating the gut microbiota during the early stages of prefrailty and understanding its behavi...

The excitation‐inhibition imbalance manifesting as epileptic activities in Alzheimer's disease is gaining more and more attention, and several potentially involved cellular and molecular pathways are currently under investigation. Based on in vitro studies, dopamine D1‐type receptors in the anterior cingulate cortex and the hippocampus have been pr...

Objectives Intensive insulin therapy provides optimal glycemic control in patients with diabetes. However, intensive insulin therapy causes so‐called iatrogenic hypoglycemia as a major adverse effect. The ventromedial hypothalamus (VMH) has been described as the primary brain area initiating the counter‐regulatory response (CRR). Nevertheless, the...

Selective serotonin reuptake inhibitors (SSRI) are common first-line treatments for major depression. However, a significant number of depressed patients do not respond adequately to these pharmacological treatments. In the present preclinical study, we demonstrate that organic cation transporter 2 (OCT2), an atypical monoamine transporter, contrib...

Studies suggest that astrocytic connexins (Cx) have an important role in the regulation of high brain functions through their ability to establish fine-tuned communication with neurons within the tripartite synapse. In light of these properties, growing evidence suggests a role of Cx in psychiatric disorders such as major depression but also in the...

Type-2 Diabetes (T2D) is characterized by insulin resistance and accompanied by psychiatric comorbidities including major depressive disorders (MDD). Patients with T2D are twice more likely to suffer from MDD and clinical studies have shown that insulin resistance is positively correlated with the severity of depressive symptoms. However, the poten...

Major depression (MD) is one of the most common psychiatric disorders worldwide. Currently, the first-line treatment for MD targets the serotonin system but these drugs, notably the selective serotonin reuptake inhibitors, usually need 4 to 6 weeks before the benefit is felt and a significant proportion of patients shows an unsatisfactory response....

The neuronal-specific SNORD115 has gathered interest because its deficiency may contribute to the pathophysiology of Prader-Willi syndrome (PWS), possibly by altering post-transcriptional regulation of the gene encoding the serotonin (HTR2C) receptor. Yet, Snord115-KO mice do not resume the main symptoms of PWS and only subtle altered A-to-I RNA ed...

Résumé La dépression majeure (DM) est une pathologie psychiatrique reposant sur différents mécanismes neurobiologiques. Parmi ces mécanismes, on trouve une hypersensibilité de l’axe hypothalamo-hypophyso-surrénalien et des modifications de différents processus de type inflammation et stress oxydatif. Différents arguments suggèrent que ces mécanisme...

Apelin is a small peptide secreted by the adipose tissue notably in conditions of obesity-induced hyper-insulinemia. Apelin exerts a range of physiological functions at the periphery including the improvement of insulin sensitivity and the increase of muscle strength or cardiac contractibility. Interestingly, the brain is endowed with a high densit...

The incidence of depression and anxiety is amplified by obesity. Mounting evidence reveals that the psychiatric consequences of obesity stem from poor diet, inactivity, and visceral adipose accumulation. Resulting metabolic and vascular dysfunction, including inflammation, insulin and leptin resistance, and hypertension, have emerged as key risks t...

Tissue repair after injury in adult mammals, usually results in scarring and loss of function in contrast to lower vertebrates such as the newt and zebrafish that regenerate. Understanding the regulatory processes that guide the outcome of tissue repair is therefore a concerning challenge for regenerative medicine. In multiple regenerative animal s...

The idea that insulin could influence emotional behaviours has long been suggested. However, the underlying mechanisms have yet to be solved and there is no direct and clear‐cut evidence demonstrating that such action involves brain serotonergic neurones. Indeed, initial arguments in favour of the association between insulin, serotonin and mood ari...

Astrocytes were traditionally regarded as cells important to neuronal activity, providing both metabolic and structural supports. Recent evidence suggests that they may also play a crucial role in the control of higher brain functions. In keeping with this hypothesis, it is now well accepted that astrocytes contribute to stress but also react to an...

Capillary electrophoresis (CE) coupled to light emitting diode induced fluorescence detection (LEDIF) is a robust and sensitive technique used for amino acids (AA) analysis in biological media, after labeling with 3‐(4‐carboxybenzoyl)quinoline‐2‐carboxaldehyde (CBQCA). We wanted to quantitate in plasma tryptophan (Trp), tyrosine (Tyr), valine (Val)...

The forced swim stress test (FST) is widely used for screening pharmacological or non-pharmacological strategies with potential antidepressant activities. Recent data have suggested that repeated FST for five consecutive days (i.e., 5d-RFSS) could be used to generate a robust depressive-like phenotype in mice. However, the face, construct, and pred...

Introduction: Several studies have suggested that diet, especially one enriched in microbiota-fermented fibers or fat, regulates behavior. The underlying mechanisms are currently unknown. We previously reported that certain macronutrients (fermentable fiber and protein) regulate energy homeostasis via the activation of intestinal gluconeogenesis (...

La dépression majeure est une pathologie psychiatrique reposant sur différents mécanismes neurobiologiques. Parmi ces mécanismes, on trouve une hypersensibilité de l’axe hypothalamo-hypophyso-surrénalien associée à un excès de cortisol dans le sang et un déficit de neurotransmission monoaminergique. Ainsi, l’efficacité thérapeutique des antidépress...

Aim Impairments in cerebral structure and cognitive performance in chronic heart failure (CHF) are critical components of its comorbidity spectrum. Autonomic afferents that arise from cardiac sensory fibres show enhanced activity with CHF. Desensitization of these fibers by local application of resiniferatoxin (RTX) during myocardial infarction (MI...

SNORD115 has been proposed to promote the activity of serotonin (HTR2C) receptor via its ability to base-pair with its pre-mRNA and regulate alternative RNA splicing and/or A-to-I RNA editing. Because SNORD115 genes are deleted in most patients with the Prader-Willi syndrome (PWS), diminished HTR2C receptor activity could contribute to the impaired...

SNORD115 has been proposed to promote the activity of serotonin (HTR2C) receptor via its ability to base-pair with its pre-mRNA and regulate alternative RNA splicing and/or A-to-I RNA editing. Because SNORD115 genes are deleted in most patients with the Prader-Willi syndrome (PWS), diminished HTR2C receptor activity could contribute to the impaired...

In the present study, we examined the neurobehavioral effects of a sensory functional food ingredient mainly based on Citrus sinensis extracts (D11399) using a battery of tests recapitulating various endophenotypes of depression such as anxiety in the open field (OF), the elevated plus-maze (EPM), and the novelty suppressed feeding (NSF), self-care...

Aging is the major risk factor for the development of chronic diseases. After decades of research focused on extending lifespan, current efforts seek primarily to promote healthy aging. Recent advances suggest that biological processes linked to aging are more reliable than chronological age to account for an individual's functional status, i.e. fr...

Donepezil (DPZ) is an acetylcholinesterase inhibitor used in Alzheimer’s disease to restore cognitive functions but is endowed with limited efficacy. Recent studies pointed out the implication of astroglial networks in cognitive processes, notably via astrocyte connexins (Cxs), proteins involved in gap junction intercellular communications. Hence,...

Current antidepressants act principally by blocking monoamine reuptake by high-affinity transporters in the brain. However, these antidepressants show important shortcomings such as slow action onset and limited efficacy in nearly a third of patients with major depression disorder. Here, we report the development of a prodrug targeting organic cati...

Type-2 Diabetes mellitus (T2DM) is mainly characterized by insulin-resistance and often accompanied by comorbidities such as major depressive disorders (MDD). Indeed, patients with T2DM are twice more likely to suffer from MDD and clinical studies have shown that insulin resistance is positively correlated with the severity of depressive symptoms....

Aim: Astroglial connexins (Cxs) 30 and 43 are engaged in gap junction and hemichannel activities. Evidence suggests that these functional entities contribute to regulating neurotransmission, thereby influencing brain functions. In particular, preclinical and clinical findings highlight a role of Cx43 in animal models of depression. However, the ro...

Astrocytes are glial cells organized in dynamic and structured networks in the brain. These plastic networks, involving key proteins such as connexin 43 (Cx43), are engaged in fine neuronal tuning and have recently been considered as emerging therapeutic targets in central nervous system disorders. We developed and validated a new application of th...

Managing severe acute nociceptive pain in buprenorphine-maintained individuals for opioid use disorder management is challenging owing to the high affinity and very slow dissociation of buprenorphine from μ-opioid receptors that hinders the use of full agonist opioid analgesics. In a translational approach, the aim of this study was to use an anima...

Background and aims: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and erratic bowel habits. A diet low in fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs) can reduce symptoms of IBS, possibly by reducing microbial fermentation products. We investigated whether ingestion of FODMAPs can induce IBS-like...

Background: Activation of serotonin (5-HT) type 4 receptors (5-HT4Rs) has been shown to have anxiolytic effects in a variety of animal models. Characterizing the circuits responsible for these effects should offer insights into new approaches to treat anxiety. Methods: We evaluated whether acute 5-HT4R activation in glutamatergic axon terminals...

Rationale Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorders. Pregabalin acts on different neurotransmission systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pre...

RATIONALE: Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorders. Pregabalin acts on different neurotransmission systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that p...

Epidemiological studies indicate that insulin resistance (IR), a hallmark of type 2 diabetes, is associated with an increased risk of major depression. Here, we demonstrated that male mice fed a high-fat diet (HFD) exhibited peripheral metabolic impairments reminiscent of IR accompanied by elevated circulating levels of branched-chain amino acids (...

Cre/loxP recombination is a widely used approach to study gene function in vivo, using mice models expressing the Cre recombinase under the control of specific promoters or through viral delivery of Cre‐expressing constructs. A profuse literature on transgenic mouse lines points out the deleterious effects of Cre expression in various cell types an...

Astrocytes are involved in the regulation of neurotransmission which in turn, impact high brain functions such as emotionality. Accordingly, clinical studies revealed decreases in brain density of GFAP-positive cells in patients with neuropsychiatric disorders [1]. Astrocytes express proteins called connexins 43 (Cx43) that can assemble into either...

Despite significant advances in the understanding of the therapeutic activity of antidepressant drugs, treatment-resistant depression is a public health issue prompting research to identify new therapeutic strategies. Evidence strongly suggests that nutrition might exert a significant impact on the onset, the duration and the severity of major depr...

Fatty acids content in control and fish oil-enriched diet.

Fish oil-enriched diet induces anxiolytic-like activities in BDNF+/- mice. (A) Anxiety evaluated in the open field. Data are means ± SEM of the time spent in the center of the arena (ANOVA: [F(3,20) = 7.1; p = 0.002]). (B) Anxiety evaluated in the elevated plus maze. Data are means ± SEM of the time spent in the open arms (ANOVA: [F(3,20) = 2.8; p...

Introduction Le potentiel d’abus et de dépendance de la prégabaline, un médicament psychoactif indiqué notamment dans la douleur neuropathique, pourrait s’expliquer par des effets neuromodulateurs intervenant dans le circuit mésolimbique dopaminergique de la récompense. L’objectif de cette étude expérimentale était d’étudier l’implication de ce cir...

Contrary to the classical view, it is now firmly established that astrocytes can specifically regulate glutamatergic tone in various brain regions including the hippocampus. In particular, release of glutamate by astrocytes has been repeatedly demonstrated in response to glial activation. However, the mechanism and degree to which astrocytes modula...

Introduction: Irritable Bowel Syndrome (IBS) is characterized by abdominal pain, often associated with diet. Limiting the consumption of FODMAPs (fermentable oligos-, di-, mono-saccharides, and polyols), unabsorbed in the small intestine and fermented by the gut microbiota, improves symptoms in 70% of IBS patients. However, the mechanisms behind th...

Anxiety disorders are one of the most prevalent mental health conditions. Although benzodiazepines are very effective in reducing acute anxiety, their adverse effects limit their use chronically. Selective serotonin reuptake inhibitors (SSRIs) are considered to be the first line of therapy for anxiety disorders but their delayed onset of action emp...

Anxiety disorders including generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD) or phobias are the most prevalent mental pathologies across the world with a median lifetime prevalence of approximately 15%. Anxiety imposes substantial economic costs which are among the highest of all mental disorders studied. Evide...

Serotonin is a neurotransmitter involved in many psychiatric diseases. In humans, a lack of 5-HT2B receptors is associated with serotonin-dependent phenotypes, including impulsivity and suicidality. A lack of 5-HT2B receptors in mice eliminates the effects of molecules that directly target serotonergic neurons including amphetamine derivative serot...

5-HT2A receptors are G-protein coupled receptors that are widely distributed throughout the brain, most notably on neuronal and glial cells. 5-HT2A receptors have been implicated in various central physiological functions including mood regulation, memory, sleep, nociception, eating, and reward behaviors, and they are also believed to control the c...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and impaired cognitive functions. The higher incidence of AD among women indicates that sex is one of the main risk factor for developing the disease. Using the transgenic APPxPS1 mouse model of AD, we investigated sex inequality with regards to memory...

In Brief Garcia-Garcia et al. use transgenic and viral approaches to demonstrate that signaling through 5-HT 1A heteroreceptors in the medial prefrontal cortex during adolescence is critical in establishing baseline mood setpoints. SUMMARY Lifelong homeostatic setpoints for mood-related behaviors emerge during adolescence. Serotonin (5-HT) plays an...

The serotonin receptor subtypes 2 comprises 5-HT2A, 5-HT2B and 5-HT2C that are Gq-coupled receptors and display distinct pharmacological properties. Although co-expressed in some brain regions and involved in various neurological disorders, their functional interactions have not been studied yet. We report that 5-HT2 receptors can form homo and het...

Rationale Evidence links alterations in α5-containing nicotinic receptors (α5*-nAChRs) to nicotine addiction. Notably, the rs16969968 polymorphism in the α5 gene (α5SNP) increases the risk for heavy smoking and impairs nicotine-rewarding properties in mice. Additional work is needed to understand how native and polymorphic α5*-nAChRs contribute to...

Unlike classic serotonergic antidepressant drugs, ketamine, an NMDA receptor antagonist, exhibits a rapid and persistent antidepressant (AD) activity, at sub-anaesthetic doses in treatment-resistant depressed patients and in preclinical studies in rodents. The mechanisms mediating this activity are unclear. Here, we assessed the role of the brain s...

Introduction Le diabète de type 2 (DT2) peut entrainer des symptômes dépressifs. La metformine et la fluoxétine peuvent être prescrits conjointement dans la comorbidité diabète-dépression. Le but de cette étude était donc de déterminer les effets respectifs de ces agents pharmacologiques et de leur association sur le contrôle glycémique et les comp...

Introduction Plusieurs études épidémiologiques suggèrent un lien entre diabète de type 2 (DT2) et dépression. Un taux élevé de glucocorticoïdes circulants, lié à une dérégulation de l'axe hypothalamique-hypophysaire-adrénalien (HPA), pourrait être un mécanisme commun aux deux pathologies. La néoglucogenèse intestinale (NGI) a des effets bénéfiques...

Introduction Différentes études l révèlent que le diabète de type 2 est souvent associé à des troubles de la mémoire. Des études épidémiologiques montrent également que le diabète double le risque de développer la maladie d'Alzheimer (MA). Quel est le rôle de l'insuline dans le cerveau, comment une résistance à l'insuline chez les patients diabétiq...

Clinical and preclinical studies have implicated glial anomalies in major depression. Conversely, evidence suggests that the activity of antidepressant drugs is based, at least in part, on their ability to stimulate density and/or activity of astrocytes, a major glial cell population. Despite this recent evidence, little is known about the mechanis...

5-Hydroxytryptamine 2A receptors (5-HT2A-Rs) are G-protein coupled receptors. In agreement with their location in the brain, they have been implicated not only in various central physiological functions including memory, sleep, nociception, eating and reward behaviors, but also in many neuropsychiatric disorders. Interestingly, a bidirectional link...

Introduction Une alimentation riche en graisse entraîne des perturbations métaboliques associées à des troubles psychiatriques. Toutefois, l’impact des traitements antidépresseurs dans la comorbidité diabète/dépression reste peu documenté. Notre étude vise à comparer les effets d’un inhibiteur sélectif de recapture de la sérotonine, le escitalopram...

Sleep/wake disorders are frequently associated with anxiety and depression and to elevated levels of cortisol. Even though these alterations are increasingly sought in animal models, no study has investigated the specific effects of chronic corticosterone (CORT) administration on sleep. We characterized sleep/wake disorders in a neuroendocrine mous...

Interactions between genetic and environmental factors, like exposure to stress, have an important role in the pathogenesis of mood-related psychiatric disorders, such as major depressive disorder. The polyspecific organic cation transporters (OCTs) were shown previously to be sensitive to the stress hormone corticosterone in vitro, suggesting that...

Background Chronic neuropathic pain can lead to anxiety and depression. Drugs that block reuptake of serotonin, norepinephrine and/or dopamine are widely used to treat depression, and have emerged as useful drugs in the treatment of neuropathic pain. This study compared the acute antinociceptive effects of NS18283, a novel triple monoamine reuptake...

Sleep/wake disorders are frequently associated with anxiety and depression and to elevated levels of cortisol. Even though these alterations are increasingly sought in animal models, no study has investigated the specific effects of chronic corticosterone administration on sleep. We characterized sleep/wake disorders in a neuroendocrine mouse model...

Introduction Des études épidémiologiques suggèrent que l’anxiété/dépression et le diabète de type 2 (DT2) sont étroitement liés. Cependant, peu d’études précliniques appuient ce concept, ce qui renforce la nécessité de développer un modèle animal de la comorbidité entre DT2 et comportement anxio/dépressif. Le but de ce projet est de déterminer si l...

This monograph is a collection of selected articles on the subject of mood disorders such as depression and schizophrenia. It is divided into 3 sections: 1) Research methods in psychopharmacology - which highlights some established experimental techniques to study mood disorders in human and relevant animal models, 2) Pathophysiology of mood disord...

Des données nombreuses mais contradictoires existent à l’heure actuelle sur l’implication du récepteur 2A à la sérotonine (5-HT2AR), codé par le gène HTR2A, dans le trouble dépressif majeur unipolaire [1,3]. Dans notre étude, nous combinons des données cliniques et précliniques pour déterminer l’impact d’une diminution de la transmission sérotonine...

SSRIs are commonly prescribed for the treatment of major depressive episodes (MDE). However, 50% of patients do not respond to these medications. Although evidence incriminates the overactivation of 5-HT1A autoreceptor in both (MDE) and poor antidepressant response, others serotonergic receptors could be recruited. This study first examined the ef...

Antidepressant drugs such as the serotonin (5-HT)/norepinephrine (NE) and/or dopamine (DA) reuptake inhibitors have been shown to activate the monoaminergic neurotransmission in various brain regions such as the amygdala, frontal cortex or hippocampus. Although this property is well established, the post-synaptic mechanisms by which these pharmacol...

Vortioxetine (Lu AA21004) is an investigational novel antidepressant with multimodal activity that functions as a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter in vitro. Here we explore its anxiolytic and antidepressant potential in adult mice. Vortioxetin...

at the 17th Annual Meeting of French Society of Pharmacology and Therapeutics, the 80th Annual Meeting of Society of Physiology, the 34th Pharmacovigilance Meeting, the 14th APNET Seminar and the 11th CHU CIC Meeting, 22-24 April 2013, Angers, France.

The therapeutic activity of selective serotonin (5-HT) reuptake inhibitors (SSRIs) relies on long-term adaptation at pre- and post-synaptic levels. The sustained administration of SSRIs increases the serotonergic neurotransmission in response to a functional desensitization of the inhibitory 5-HT1A autoreceptor in the dorsal raphe. At nerve termina...

Introduction Le diabète de type 2 touche environ 3 % de la population française et le nombre de personnes atteintes est en progression constante. Des études épidémiologiques révèlent que la dépression constitue une des complications fréquemment observées au cours de la maladie. Par ailleurs, un état dépressif augmenterait le risque de diabète souli...

Evidence suggests that the serotonin 2A receptor (5-HT2AR) modulates the therapeutic activity of selective serotonin reuptake inhibitors (SSRIs). Indeed, among the genetic factors known to influence the individual response to antidepressants, the HTR2A gene has been associated with SSRIs response in depressed patients. However, in these pharmacogen...