Two polygenic mouse models of major depressive disorders identify TMEM161B as a potential biomarker of disease in humans.

Treatments are only partially effective in major depressive disorders (MDD) but no biomarker exists to predict symptom improvement in patients. Animal models are essential tools in the development of antidepressant medications, but while recent genetic studies have demonstrated the polygenic contribution to MDD, current models are limited to either mimic the effect of a single gene or environmental factor. We developed in the past a model of depressive-like behaviors in mice (H/Rouen), using selective breeding based on behavioral reaction after an acute mild stress in the tail suspension test.

Ultrafine Particles Issued from Gasoline-Fuels and Biofuel Surrogates Combustion: A Comparative Study of the Physicochemical and Toxicological Effects.

Gasoline emissions contain high levels of pollutants, including particulate matter (PM), which are associated with several health outcomes. Moreover, due to the depletion of fossil fuels, biofuels represent an attractive alternative, particularly second-generation biofuels (B2G) derived from lignocellulosic biomass. Unfortunately, compared to the abundant literature on diesel and gasoline emissions, relatively few studies are devoted to alternative fuels and their health effects.

Desloratadine, an FDA-approved cationic amphiphilic drug, inhibits SARS-CoV-2 infection in cell culture and primary human nasal epithelial cells by blocking viral entry.

The 2019 global coronavirus (COVID-19) pandemic has brought the world to a grinding halt, highlighting the urgent need for therapeutic and preventive solutions to slow the spread of emerging viruses. The objective of this study was to assess the anti-SARS-CoV-2 effectiveness of 8 FDA-approved cationic amphiphilic drugs (CADs). SARS-CoV-2-infected Vero cells, Calu-3 cells and primary Human Nasal Epithelial Cells (HNEC) were used to investigate the effects of CADs and revealed their antiviral mode of action.

Development of a standardized in vitro approach to evaluate microphysical, chemical, and toxicological properties of combustion-derived fine and ultrafine particles.

Ultrafine particles represent a growing concern in the public health community but their precise role in many illnesses is still unknown. This lack of knowledge is related to the experimental difficulty in linking their biological effects to their multiple properties, which are important determinants of toxicity. Our aim is to propose an interdisciplinary approach to study fine (FP) and ultrafine (UFP) particles, generated in a controlled manner using a miniCAST (Combustion Aerosol Standard) soot generator used with two different operating conditions (CAST1 and CAST3).

Validation of a Fast and Simple HPLC-UV Method for the Quantification of Adenosine Phosphates in Human Bronchial Epithelial Cells.

A new HPLC method for the simultaneous quantitative analysis of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) was developed and validated. ATP, ADP, and AMP were extracted from human bronchial epithelial cells with a rapid extraction procedure and separated with a C18 column (3 × 150 mm, 2.7 µm) using isocratic elution with a mobile phase consisting of 50 mM of potassium hydrogen phosphate (pH 6.

Antidepressant-like effect of low dose of scopolamine in the H/Rouen genetic mouse model of depression.

Rodent models of depression are useful for the investigation of cellular and neuronal mechanisms of antidepressant drugs and for the discovery of potential new targets. In this study, we examined the antidepressant-like effect of scopolamine, a non-selective muscarinic antagonist, in a genetic mouse model of depression obtained through a selective breeding strategy and called H/Rouen. In this model, we observed that scopolamine was active both in males and females at a lower dose (0.

Nitrogen Dioxide Inhalation Exposures Induce Cardiac Mitochondrial Reactive Oxygen Species Production, Impair Mitochondrial Function and Promote Coronary Endothelial Dysfunction.

Traffic air pollution is a major health problem and is recognized as an important risk factor for cardiovascular (CV) diseases. In a previous experimental study, we showed that diesel exhaust (DE) exposures induced cardiac mitochondrial and CV dysfunctions associated with the gaseous phase. Here, we hypothesized that NO exposures to levels close to those found in DE induce a mitochondrial reactive oxygen species (ROS) production, which contribute to an endothelial dysfunction, an early indicator for numerous CV diseases.

An integrated functional and transcriptomic analysis reveals that repeated exposure to diesel exhaust induces sustained mitochondrial and cardiac dysfunctions.

Diesel exhaust (DE) contributes to air pollution, an important risk factor for cardiovascular diseases. However, the mechanisms by which DE exposure induces cardiovascular dysfunction remain unknown and there is still debate on the contribution of the primary particulate matter (PM) fraction compared to the gaseous phase. Although the mitochondria play a key role in the events leading to cardiovascular diseases, their role in DE-induced cardiovascular effects has not been investigated.

Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A Receptor in Hippocampal Glutamate Synapses.

Caffeine prophylactically prevents mood and memory impairments through adenosine A receptor (AR) antagonism. AR antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.

Enhanced Cocaine-Associated Contextual Learning in Female H/Rouen Mice Selectively Bred for Depressive-Like Behaviors: Molecular and Neuronal Correlates.

Background: Major depression has multiple comorbidities, in particular drug use disorders, which often lead to more severe and difficult-to-treat illnesses. However, the mechanisms linking these comorbidities remain largely unknown.

Methods: We investigated how a depressive-like phenotype modulates cocaine-related behaviors using a genetic model of depression: the Helpless H/Rouen (H) mouse.

GABAB(1) receptor subunit isoforms differentially regulate stress resilience.

Stressful life events increase the susceptibility to developing psychiatric disorders such as depression; however, many individuals are resilient to such negative effects of stress. Determining the neurobiology underlying this resilience is instrumental to the development of novel and more effective treatments for stress-related psychiatric disorders. GABAB receptors are emerging therapeutic targets for the treatment of stress-related disorders such as depression.

The H/Rouen mouse model displays depression-like and anxiety-like behaviors.

Cardinal symptoms of depression include helplessness and anhedonia. In addition, depression and anxiety are often comorbid disorders. H/Rouen mice, a genetic mouse model of depression, display helpless behavior in the tail suspension test, whereas non-helpless NH/Rouen mice show the opposite behavior.

Hippocampal group III mGlu receptor mRNA levels are not altered in specific mouse models of stress, depression and antidepressant action.

The neurotransmitter glutamate is increasingly being implicated as playing a role in the molecular pathology underlying depression. The group III family of metabotropic glutamate (mGlu) receptors (mGlu(4,) mGlu(7) and mGlu(8) receptors) remains the most poorly investigated of all glutamate receptors in this regard, despite early research efforts showing that they may be major players in stress-induced pathology, genetic vulnerability to the onset of depression and in the action of pharmacotherapies. To redress this deficit, we investigated whether the mRNA levels of the group III mGlu receptors display sensitivity to the preclinical stress models' chronic immobilisation stress (CIS) in BALB/c mice and chronic social defeat in BALB/c and C57BL/6j mice.

Behaviour of a genetic mouse model of depression in the learned helplessness paradigm.

Rationale: H/Rouen (displaying a helpless phenotype in the tail suspension test) mice exhibiting features of depressive disorders and NH/Rouen (displaying non-helpless phenotype) mice were previously created through behavioural screening and selective breeding. Learned helplessness (LH), in which footshock stress induces a coping deficit, models some aspects of depression in rodents, but so far, fewer LH studies have been performed in mice than in rats.

Objectives: To study H/Rouen and NH/Rouen in the LH paradigm.

Adenosine A2A receptor deficient mice are partially resistant to limbic seizures.

The neuromodulator adenosine, acting through activation of four defined metabotropic receptors called A(1), A(2A), A(2B) and A(3,) has been proposed as an endogenous anticonvulsant. Here, the consequences of deleting the adenosine A(2A) receptor have been examined in different experimental models of epilepsy. A(2A)R KO mice were not protected against seizures originating from brainstem structures, namely electroshock-induced seizures.

Evidence for the involvement of the adenosine A(2A) receptor in the lowered susceptibility to pentylenetetrazol-induced seizures produced in mice by long-term treatment with caffeine.

Long-term caffeine intake has been reported to decrease the susceptibility to convulsants in mice. Occurrence of seizures following long-term oral administration of caffeine (0.3g/l) was investigated using adenosine A(2A) receptor knockout (A(2A)R KO) and control (A(2A)R WT) mice.

Behavioral characterization of CD26 deficient mice in animal tests of anxiety and antidepressant-like activity.

CD26 exhibits a dipeptidylpeptidase-IV function (DPPIV) which regulates neuropeptide activity by N-terminal processing. Because abnormal plasma DPPIV was associated in mammals with behavioral changes, we examined the behavior of CD26-/- mice resulting from targeted inactivation of the gene. These animals had a decreased immobility in the forced swim and tail suspension tests, indicating a reduced depression-like behavior.

Alterations in 5-HT1B receptor function by p11 in depression-like states.

The pathophysiology of depression remains enigmatic, although abnormalities in serotonin signaling have been implicated. We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface.