Search results for "DEP"

Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels

2016

Abstract Background Disruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB 1 receptors has been linked to depression in humans and depression-like behaviors in mice. The two main endogenous cannabinoids, anandamide and 2-arachidonoyl glycerol (2-AG), are produced on demand from phospholipids. The pathways and enzymes involved in endocannabinoid biosynthesis thus play a major role in regulating the activity of this system. This study investigates the role of the main 2-AG producing enzyme diacylglycerol lipase α (DAGL-α). Methods We generated and used knockout mice lacking DAGL-α ( Dagla −/− ) to assess the behavioral consequences of reduce…

Neurotrophic and neuroprotective effects of muscle contraction

2016

Background: Physical activity has been shown to be associated with reduced risk of coronary heart disease but the same effect seems to be produced in neurological diseases. Objective: In this review, we focused on the interplay between physical activity and some neurological conditions (Stroke, dementia, epilepsy, headache, Parkinson’ s disease, amyotrophic lateral sclerosis, multiple sclerosis, insomnia, depression and anxiety) with the aim of describing the potential role of physical activity in the prevention of such diseases and the physiological mechanisms involved in these processes. Results: Despite a growing body of evidence which reveals that physical activity is able to reduce the…

Crucial role for Nox2 and sleep deprivation in aircraft noise-induced vascular and cerebral oxidative stress, inflammation, and gene regulation

2018

Abstract Aims Aircraft noise causes endothelial dysfunction, oxidative stress, and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension, and stroke. The underlying mechanisms are not well understood. Herein, we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise protocols (around-the-clock, sleep/awake phase noise) on vascular and cerebral complications in mice. Methods and results C57BL/6j and Nox2 −/− (gp91phox −/−) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep/awake phases for 1, 2, and 4 days. Adverse effec…

Influence of mental stress and environmental toxins on circadian clocks : implications for redox regulation of the heart and cardioprotection

2020

Risk factors in the environment such as air pollution and mental stress contribute to the development of chronic non-communicable disease. Air pollution was identified as the leading health risk factor in the physical environment, followed by water pollution, soil pollution/heavy metals/chemicals and occupational exposures, however neglecting the non-chemical environmental health risk factors (e.g. mental stress and noise). Epidemiological data suggest that environmental risk factors are associated with higher risk for cardiovascular, metabolic and mental diseases, including hypertension, heart failure, myocardial infarction, diabetes, arrhythmia, stroke, depression and anxiety disorders. W…

The Burden of Respiratory Syncytial Virus Disease in Pre-Term Infants

2015

This mini-review summarises the risk factors for acquiring Respiratory Syncitial Virus (RSV) infection, and describes the harmful effects of the infection in pre-term infants. Moreover, theoretical considerations are discussed for the prevention of RSV infection in high-risk infant categories, such as pre-term infants. Background: Neonates positive for RSV are more prone to severe infection than neonates infected with other common respiratory viruses. Despite RSV infection being more common in late neonates than in early ones, pre-term infants ≤ 35 wk gestational age (GA) are at high risk for developing severe RSV disease. Efforts to prevent infection include case management, vaccination an…

Chronically elevated branched chain amino acid levels are pro-arrhythmic.

2022

Aim. Cardiac arrhythmias comprise a major health and economic burden and are associated with significant morbidity and mortality, including cardiac failure, stroke and sudden cardiac death (SCD). Development of efficient preventive and therapeutic strategies is hampered by incomplete knowledge of disease mechanisms and pathways. Our aim is to identify novel mechanisms underlying cardiac arrhythmia and SCD using an unbiased approach. Methods and Results. We employed a phenotype-driven N-ethyl-N-nitrosourea (ENU) mutagenesis screen and identified a mouse line with a high incidence of sudden death at young age (6-9 weeks) in the absence of prior symptoms. Affected mice were found to be homozyg…

2018

There are two important gaps of knowledge in depression treatment, namely the lack of biomarkers predicting response to antidepressants and the limited knowledge of the molecular mechanisms underlying clinical improvement. However, individually tailored treatment strategies and individualized prescription are greatly needed given the huge socio-economic burden of depression, the latency until clinical improvement can be observed and the response variability to a particular compound. Still, individual patient-level antidepressant treatment outcomes are highly unpredictable. In contrast to other therapeutic areas and despite tremendous efforts during the past years, the genomics era so far ha…

Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression

2016

SummaryImmune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration. Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitula…

Lateral Habenula 5-HT2C Receptor Function Is Altered by Acute and Chronic Nicotine Exposures

2021

Serotonin (5-HT) is important in some nicotine actions in the CNS. Among all the 5-HT receptors (5-HTRs), the 5-HT2CR has emerged as a promising drug target for smoking cessation. The 5-HT2CRs within the lateral habenula (LHb) may be crucial for nicotine addiction. Here we showed that after acute nicotine tartrate (2 mg/kg, i.p.) exposure, the 5-HT2CR agonist Ro 60-0175 (5–640 µg/kg, i.v.) increased the electrical activity of 42% of the LHb recorded neurons in vivo in rats. Conversely, after chronic nicotine treatment (6 mg/kg/day, i.p., for 14 days), Ro 60-0175 was incapable of affecting the LHb neuronal discharge. Moreover, acute nicotine exposure increased the 5-HT2CR-immunoreactive (IR)…

Role of p27Kip1 as a transcriptional regulator

2018

The protein p27Kip1 is a member of the Cip/Kip family of cyclin-dependent kinase (Cdk) inhibitors. It interacts with both the catalytic and the regulatory subunit (cyclin) and introduces a region into the catalytic cleave of the Cdk inducing its inactivation. Its inhibitory capacity can be modulated by specific tyrosine phosphorylations. p27Kip1 also behaves as a transcriptional regulator. It associates with specific chromatin domains through different transcription factors. ChIP on chip, ChIP-seq and expression microarray analysis allowed the identification of the transcriptional programs regulated by p27Kip1. Thus, important cellular functions as cell division cycle, respiration, RNA proc…