A5081516303- Cannabis and Cannabinoid Research
- Neuroscience and Neuropharmacology Research
- Sleep and Wakefulness Research
- Neuroscience of respiration and sleep
- Neurotransmitter Receptor Influence on Behavior
- Ion Channels and Receptors
- Diet, Metabolism, and Disease
- Pancreatic function and diabetes
- Biochemical effects in animals
- Prenatal Substance Exposure Effects
- Blood Coagulation and Thrombosis Mechanisms
- Alcohol Consumption and Health Effects
- Pain Mechanisms and Treatments
- Forensic Toxicology and Drug Analysis
- GABA and Rice Research
- Dietary Effects on Health
- Birth, Development, and Health
- Circadian rhythm and melatonin
- Neural dynamics and brain function
- Biochemical Analysis and Sensing Techniques
- Preterm Birth and Chorioamnionitis
- Reproductive System and Pregnancy
- Pregnancy and preeclampsia studies
- Receptor Mechanisms and Signaling
- Regulation of Appetite and Obesity
Indiana University Bloomington
2016-2025
Médecins du Monde
2023
Unit of Functional and Adaptive Biology
2023
Université Paris Cité
2023
Centre National de la Recherche Scientifique
2023
Glasgow Royal Infirmary
2015-2020
Indiana University
2015-2019
The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because the lack mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator pressure-induced damage associated with ventilator-induced injury, heart failure, and infarction. Here, we examined effects two novel TRPV4 inhibitors mice exposed hydrochloric acid, mimicking...
Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that inhibits cell proliferation and induces death of cancer cells activated immune cells. It not an agonist the classical CB1/CB2 receptors mechanism by which it functions unknown. Here, we studied effects CBD on various mitochondrial in BV-2 microglial Our findings indicate treatment leads to biphasic increase intracellular calcium levels changes function morphology leading death. Density gradient fractionation analysis mass...
Abstract Orexins are associated with drug relapse in rodents. Here, we show that acute restraint stress mice activates lateral hypothalamic (LH) orexin neurons, increases levels of A and 2-arachidonoylglycerol (2-AG) the ventral tegmental area (VTA), reinstates extinguished cocaine-conditioned place preference (CPP). This stress-induced reinstatement cocaine CPP depends on type 1 receptors (OX1Rs), cannabinoid (CB1Rs) diacylglycerol lipase (DAGL) VTA. In dopaminergic neurons VTA slices,...
Introduction: The high prevalence of adolescent cannabis use, the association between this use and later psychiatric disease, increased access to high-potency highlight need for a better understanding long-term effects on cognitive behavioral outcomes. Furthermore, increasing Δ9-tetrahydrocannabinol (THC) in is accompanied by decrease cannabidiol (CBD), thus an interactions CBD THC neurodevelopmental also important. current study examined immediate consequences THC, CBD, their combination...
A family of endogenous lipids, structurally analogous to the cannabinoid, N-arachidonoyl ethanolamine (Anandamide), and called N-acyl amides have emerged as a biologically active compounds at TRP receptors. are constructed from an acyl group amine via amide bond. This same structure can be modified by changing either fatty acid or form potentially hundreds lipids. More than 70 been identified in nature. We ongoing studies aimed isolating characterizing additional members both central...
Journal Article Experimental colitis in mice is attenuated by changes the levels of endocannabinoid metabolites induced selective inhibition fatty acid amide hydrolase (FAAH) Get access M. Sałaga, Sałaga aDepartment Biomolecular Chemistry, Faculty Medicine, Medical University Lodz, Poland Search for other works this author on: Oxford Academic PubMed Google Scholar A. Mokrowiecka, Mokrowiecka bDepartment Digestive Tract Diseases, P.K. Zakrzewski, Zakrzewski cDepartment Cytobiochemistry,...
There are currently more than 15 million preterm births each year. We propose that gene-environment interaction is a major contributor to birth. To address this experimentally, we generated mouse model with uterine deletion of Trp53, which exhibits approximately 50% incidence spontaneous birth due premature decidual senescence increased mTORC1 activity and COX2 signaling. Here provide evidence predisposition provoked in 100% females exposed mild inflammatory insult LPS, revealing the high...
Inflammation and oxidative stress are known risk factors for preterm birth (PTB); however, the mechanisms pathways that influence this condition not fully described. Previously, we showed mTORC1 signaling is increased in mice harboring a uterine-specific deletion of transformation-related protein 53 (p53d/d mice), which exhibit premature decidual senescence triggers spontaneous inflammation-induced PTB. Treatment with inhibitor rapamycin reduced incidence PTB p53d/d mice. Decidual heightened...
Purpose: It has been known for nearly 50 years that cannabis and the psychoactive constituent Δ9-tetrahydrocannabinol (THC) reduce intraocular pressure (IOP). Elevated IOP remains chief hallmark therapeutic target glaucoma, a major cause of blindness. THC likely acts via one cannabinoid-related receptors (CB1, CB2, GPR18, GPR119, GPR55) but this never determined explicitly. Cannabidiol (CBD) is second found to be without effect on in most studies. Methods: Effects topically applied CBD were...
For many G-protein-coupled receptors (GPCRs), including cannabinoid receptor 1 (CB R), desensitization has been proposed as a principal mechanism driving initial tolerance to agonists. GPCR typically requires phosphorylation by kinase (GRK) and interaction of the phosphorylated with an arrestin. In simple model systems, CB R is desensitized GRK at two serine residues (S426 S430). However, role these in dependence for cannabinoids vivo was unclear. Therefore, we generated mice where S426 S430...
Fatty-acid amide hydrolase (FAAH) is the major enzyme responsible for degradation of anandamide, an endocannabinoid. Pharmacological inhibition or genetic deletion FAAH (FAAH KO) produces antinociception in preclinical pain models that largely attributed to anandamide-induced activation cannabinoid receptors. However, metabolizes a wide range structurally related, biologically active lipid signaling molecules whose functions remain unknown. Some these endogenous lipids, including anandamide...
Muscle wasting, anorexia, and metabolic dysregulation are common side-effects of cytotoxic chemotherapy, having a dose-limiting effect on treatment efficacy, compromising quality life mortality. Extracts Cannabis sativa, analogues the major phytocannabinoid Δ9-tetrahydrocannabinol, have been used to ameliorate chemotherapy-induced appetite loss nausea for decades. However, psychoactive limit their clinical utility, they little efficacy against weight loss. We recently established that...
Introduction: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are bioactive cannabinoids. We recently showed that acute THC administration drives region-dependent changes in the mouse brain lipidome. This study tested hypothesis cell lines representing types present central nervous system (CNS), neurons (N18 cells), astrocytes (C6 glioma microglia (BV2 cells) would respond differently to THC, CBD, or their combination. experimental strategy also allowed us test CBD metabolized if...
Purpose: The diurnal cycling of intraocular pressure (IOP) was first described in humans more than a century ago. This is preserved other species. physiologic underpinning this variation IOP remains mystery, even though elevated indicated most forms glaucoma, common cause blindness. Once identified, the system that underlies would represent natural target for therapeutic intervention. Methods: Using normotensive mice, we measured regulation ocular lipid species by enzymes fatty acid amide...
The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced schizophrenia (SZ), particularly to 40 Hz stimulation. gamma frequency ASSR deficit has been attributed N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether NMDAR antagonist, phencyclidine (PCP), produced similar deficits rats. EEG was recorded from awake rats via intracranial electrodes overlaying auditory cortex and at vertex of skull. ASSRs click trains were 10, 20, 30, 40, 50,...
Background and Purpose Neuropathic pain is commonly treated with GABA analogues, steroids or non‐steroidal anti‐inflammatory drugs ( NSAIDs ). inhibit one more COX isozymes but chronic inhibition paradoxically increases gastrointestinal inflammation risk of unwanted cardiovascular events. The cannabinoids also have analgesic properties reduce neuropathic in animal models. present study investigated the effects inhibiting both monoacylglycerol lipase MAGL ) enzymes, using low doses...
Cannabinoids, such as Δ9-THC, act through an endogenous signaling system in the vertebrate eye that reduces IOP via CB1 receptors. Endogenous cannabinoid (eCB) ligand, 2-arachidonoyl glycerol (2-AG), likewise activates and is metabolized by monoacylglycerol lipase (MAGL). We investigated ocular 2-AG its regulation MAGL therapeutic potential of harnessing eCBs to lower IOP.We tested effect topical application blockers normotensive mice examined changes eCB-related lipid species eyes spinal...
Derived from arachidonic acid (AA), the endogenous cannabinoid (eCB) 2-arachidonoyl glycerol (2-AG) is a substrate for αβ-hydrolase domain 12 (ABHD12). Loss-of-function mutations of ABHD12 are associated with neurodegenerative disorder polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC). knockout (KO) mice show PHARC-like behaviors in older adulthood. Here, we test hypothesis that deletion age-dependently regulates bioactive lipids CNS. Lipidomics analysis...