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Liqing Chen, Yan Yan, Tinggui Chen, Liwei Zhang, Xiaoxia Gao, Chenhui Du, Huizhi Du
In the study, the neuroprotectivities of forsythiaside, a main constituent of Forsythia suspensa (Thunb.) Vahl (F. suspensa, Lianqiao in Chinese), were investigated in the hippocampal slices. Forsythiaside suppressed the overexpression of cyclooxygenase-2 (COX-2) and monoacylglycerol lipase (MAGL) proteins induced by β-amyloid (Aβ25-35 ) to upregulate the levels of 2-arachidonoylglycerol (2-AG), an endogenous endocannabinoids. Then the inhibition of forsythiaside on COX-2 was deeply studied by the molecular docking...
February 12, 2019: Neurochemistry International
Hasan Gençoğlu, Kazim Şahin, Peter M Jones
Background/aim: The polypeptide hormone insulin is essential for the maintenance of whole-body fuel homeostasis, and defects in insulin secretion and/or action are associated with the development of type 1 and type 2 diabetes. The aim of this study was to assess the role of some G-protein coupled receptors (GPCRs), GPR54, GPR56, and GPR75, and cannabinoid receptors CB1R and CB2R, in the regulation of pancreatic β-cell function. Materials and methods: Insulin secretion from mouse insulinoma β-cell line (MIN6) monolayers was assessed via insulin radioimmu-noassay (RIA)...
February 11, 2019: Turkish Journal of Medical Sciences
Liliang Li, Xiaoru Dong, Chunyan Tu, Xiaoqing Li, Zhao Peng, Yiling Zhou, Dingang Zhang, Jieqing Jiang, Allen Burke, Ziqin Zhao, Li Jin, Yan Jiang
BACKGROUND AND PURPOSE: Clozapine is an atypical antipsychotic drug that is very efficacious in treating psychosis but the risk of severe cardiotoxicity limits its clinical use. The present study investigated the myocardial injury effects of clozapine and assessed the involvement of cannabinoid receptors in clozapine cardiotoxicity. EXPERIMENTAL APPROACH: The clozapine alone or in combination with selective cannabinoid receptor antagonists or agonists were used to treat mice and cardiomyocytes...
February 1, 2019: British Journal of Pharmacology
Omayma Alshaarawy, Emily Kurjan, Nguyen Truong, L Karl Olson
OBJECTIVE: Evidence suggests that cannabinoid-1 receptor (CB1R) activation is associated with increased food intake and body weight gain. Human epidemiological studies, however, show decreased prevalence of obesity in cannabis users. Given the overlapping and complementary functions of the cannabinoid receptors (CB1R and CB2R), mice lacking CB2R and mice lacking both CB1R and CB2R were studied. METHODS: A high-fat diet was used to study metabolic changes in male mice lacking CB2R (CB2-/- ) or lacking both CB1R and CB2R (double-knockout [CB-DKO]) compared with wild-type mice...
January 30, 2019: Obesity
Alba Navarro-Romero, Anna Vázquez-Oliver, Maria Gomis-González, Carlos Garzón-Montesinos, Rafael Falcón-Moya, Antoni Pastor, Elena Martín-García, Nieves Pizarro, Arnau Busquets-Garcia, Jean-Michel Revest, Pier-Vincenzo Piazza, Fátima Bosch, Mara Dierssen, Rafael de la Torre, Antonio Rodríguez-Moreno, Rafael Maldonado, Andrés Ozaita
Intellectual disability is the most limiting hallmark of Down syndrome, for which there is no gold-standard clinical treatment yet. The endocannabinoid system is a widespread neuromodulatory system involved in multiple functions including learning and memory processes. Alterations of this system contribute to the pathogenesis of several neurological and neurodevelopmental disorders. However, the involvement of the endocannabinoid system in the pathogenesis of Down syndrome has not been explored before. We used the best-characterized preclinical model of Down syndrome, the segmentally trisomic Ts65Dn model...
January 25, 2019: Neurobiology of Disease
Ewelina Wawryk-Gawda, Katarzyna Chłapek, Michał K Zarobkiewicz, Marta Lis-Sochocka, Patrycja Chylińska-Wrzos, Anna Boguszewska-Czubara, Mirosław A Sławiński, Anna Franczak, Barbara Jodłowska-Jędrych, Grażyna Biała
INTRODUCTION: Nicotine stimulates fibroblast proliferation while increasing inflammation and fibrosis of tissues. The cannabinoid receptor 1 (CB1R) is mainly located in the CNS, while cannabinoid receptor 2 (CB2R) is located in the immune cells within the body. CB2R regulates inflammatory processes and fibroblast function. PURPOSE: We investigated the impact of CB2R agonist, JWH 133 and the antagonist, AM630 on lung tissue, applied directly before nicotine application...
January 24, 2019: Experimental Lung Research
Reza Fartootzadeh, Fatemeh Azizi, Hojjatallah Alaei, Parham Reisi
In the present study, we have evaluated the existence of functional interaction between orexin-2 receptor (OX2R) and cannabinoid-1 receptor (CB1R) in the nucleus accumbens core (NAcc), in nicotine-induced conditioned place preference (CPP) of Wistar male rat. Nicotine (0.5 mg/kg; s.c.) in the course of conditioning, produced a significant place preference, without any effect on the locomotor activity. Intra-NAcc administration of ineffective and effective doses of TCS-OX2-29 (2 and 6 ng/rat), a selective OX2R antagonist and AM251 (10 and 50 ng/rat), a selective CB1R antagonist, showed a significant interaction between OX2R and CB1R in the acquisition of nicotine-induced CPP (p < 0...
January 16, 2019: Neuroscience Letters
Balapal S Basavarajappa, Shivakumar Subbanna
The chief psychoactive constituent of many bioactive phytocannabinoids (Δ⁸-tetrahydrocannabinol, Δ⁸-THC) found in hemp, cannabis or marijuana plants are scientifically denoted by the Latin term, Cannabis sativa , acts on cell surface receptors. These receptors are ubiquitously expressed. To date, two cannabinoid receptors have been cloned and characterized. Cannabinoid receptor type 1 (CB1R) is found to serve as the archetype for cannabinoid action in the brain. They have attracted wide interest as the mediator of all psychoactive properties of exogenous and endogenous cannabinoids and they are abundantly expressed on most inhibitory and excitatory neurons...
January 16, 2019: Brain Sciences
Oswald Boa-Amponsem, Chengjin Zhang, Somnath Mukhopadhyay, Iman Ardrey, Gregory J Cole
BACKGROUND: Recent work suggests that endocannabinoids (eCBs) may signal through the sonic hedgehog signaling pathway. We therefore hypothesized that combined ethanol and eCB exposure during defined stages of zebrafish embryogenesis will produce deficits comparable to human fetal alcohol spectrum disorder (FASD). METHODS: Zebrafish embryos were exposed to ethanol or cannabinoid agonists alone or in combination at defined developmental stages and assessed for changes in brain morphology or expression of marker genes such as pax6a...
January 16, 2019: Birth Defects Research
E R Hawken, C P Normandeau, J Gardner Gregory, B Cécyre, J-F Bouchard, K Mackie, É C Dumont
Nestled within feeding circuits, the oval (ov) region of the Bed Nucleus of the Stria Terminalis (BNST) may be critical for monitoring energy balance through changes in synaptic strength. Here we report that bidirectional plasticity at ovBNST GABA synapses was tightly linked to the caloric state of male rats, seesawing between long-term potentiation (iLTP, fed) and depression (iLTD, food restricted). L-α-lysophosphatidylinositol (LPI) acting on GPR55 receptors and 2-arachidonoylglycerol (2-AG) through CB1R were respectively responsible for fed (iLTP) and food restricted (iLTD) states...
January 7, 2019: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Chun-Wu Tung, Cheng Ho, Yung-Chien Hsu, Shun-Chen Huang, Ya-Hsueh Shih, Chun-Liang Lin
Diabetic nephropathy often leads to end-stage renal disease and life-threatening morbidities. Simple control of risk factors is insufficient to prevent the progression of diabetic nephropathy, hence the need for discovering new treatments is of paramount importance. Recently, the dysregulation of microRNAs or the cannabinoid signaling pathway has been implicated in the pathogenesis of various renal tubulointerstitial fibrotic damages and thus novel therapeutic targets for chronic kidney diseases have emerged; however, the role of microRNAs or cannabinoid receptors on diabetes-induced glomerular injuries remains to be elucidated...
January 11, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Liad Hinden, Joseph Tam
Diabetic nephropathy (DN), a distinct manifestation of diabetic kidney disease, affects approximately 30% of patients with diabetes. While most attention has been focused on glomerular changes related to DN, there is growing evidence that tubulopathy is a key feature in the pathogenesis of this disease. The renal proximal tubule cells (RPTCs) are particularly sensitive to the deleterious effect of chronic hyperglycemia. However, the cellular changes that control the dysfunction of the RPTCs are not fully understood...
January 11, 2019: Nephron
Maya R Jacobson, Jeremy J Watts, Isabelle Boileau, Junchao Tong, Romina Mizrahi
Cannabis, the most widely used illicit drug worldwide, produces psychoactive effects through its component cannabinoids, which act on the endocannabinoid system. Research on how cannabinoid exposure affects the endocannabinoid system is limited. Substantial evidence indicates cannabis use as a risk factor for psychosis, and the mechanism(s) by which this is occurring is/are currently unknown. Here, we conduct the first review of the effects of exogenous cannabinoids on the endocannabinoid system in humans with and without psychotic disorders...
January 8, 2019: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Ji Hye Han, Hanho Shin, Ju-Young Park, Jun Gi Rho, Dong Hwee Son, Ki Woo Kim, Je Kyung Seong, Sung-Hwa Yoon, Wook Kim
The overactivity of cannabinoid 1 receptor (CB1R) is associated with obesity and type 2 diabetes. First-generation CB1R antagonists, such as rimonabant, offered therapeutic advantages for the control of obesity and related metabolic abnormalities, but their therapeutic potential was limited by undesirable neuropsychiatric side effects. Here, we evaluated AJ5012 as a novel potent peripheral CB1R antagonist and, using this antagonist, investigated the role of peripheral CB1R on adipose tissue inflammation in obese mouse models...
December 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Salar Vaseghi, Vahab Babapour, Mohammad Nasehi, Mohammad-Reza Zarrindast
Lithium, a glycogen synthase kinase-3β (GSK-3β) inhibitor, prevents cannabinoid withdrawal syndrome, but there is limited data exploring the interaction between lithium and cannabinoid system on memory processes. The present study aimed to test the interaction between dorsal hippocampal (CA1 region) cannabinoid system and lithium on spatial memory in rats. Spatial memory was assessed in Morris Water Maze (MWM) apparatus by a single training session of eight trials. The results showed that pre-training intra-CA1 microinjection of ACPA, the cannabinoid type 1 receptor (CB1r) agonist, at doses of 0...
2018: EXCLI Journal
Filipa Fiel Ferreira, Filipa F Ribeiro, Rui S Rodrigues, Ana Maria Sebastião, Sara Xapelli
The adult mammalian brain can produce new neurons in a process called adult neurogenesis, which occurs mainly in the subventricular zone (SVZ) and in the hippocampal dentate gyrus (DG). Brain-derived neurotrophic factor (BDNF) signaling and cannabinoid type 1 and 2 receptors (CB1R and CB2R) have been shown to independently modulate neurogenesis, but how they may interact is unknown. We now used SVZ and DG neurosphere cultures from early (P1-3) postnatal rats to study the CB1R and CB2R crosstalk with BDNF in modulating neurogenesis...
2018: Frontiers in Cellular Neuroscience
Stephanie M Perez, Jennifer J Donegan, Angela M Boley, David D Aguilar, Andrea Giuffrida, Daniel J Lodge
Adolescent cannabis use has been implicated as a risk factor for schizophrenia; however, it is neither necessary nor sufficient. Previous studies examining this association have focused primarily on the role of the cannabinoid receptor 1 (CB1R) with relatively little known about a key regulatory protein, the cannabinoid receptor interacting protein 1 (CNRIP1). CNRIP1 is an intracellular protein that interacts with the C-terminal tail of CB1R and regulates its intrinsic activity. Previous studies have demonstrated aberrant CNRIP1 DNA promoter methylation in post-mortem in human patients with schizophrenia, and we have recently reported decreased methylation of the CNRIP1 DNA promoter in the ventral hippocampus (vHipp) of a rodent model of schizophrenia susceptibility...
December 3, 2018: Schizophrenia Research
Xiangshu Xian, Li Tang, Chengrong Wu, Liuye Huang
Background: Gastric cancer (GC) is the most common malignancy and third leading cause of cancer mortality worldwide. The identification of a sensitive biomarker as well as effective therapeutic targets for the treatment of GC is of critical importance. microRNAs play significant roles in the development of cancer and may serve as promising therapeutic targets. Methods: The mRNA and protein expression of CB1R were studied both in GC cells and tissues. GC cell lines with specific gene overexpression and knockdown vectors were constructed...
2018: OncoTargets and Therapy
Rania A A Salama, Rania M Abdelsalam, O M E Abdel-Salam, Mahmoud M Khattab, Neveen A Salem, Zakaria A El-Khyat, Fatma A Morsy, Ezz-El Din S Eldenshary
The current study aimed to evaluate the role of cannabinoid receptors in the regulation of gastric acid secretion and oxidative stress in gastric mucosa. To fulfill this aim, gastric acid secretion stimulated with histamine (5 mg/kg, subcutaneous [SC]), 2-deoxy- d-glucose (D-G) (200 mg/kg, intravenous) or -carbachol (4 μg/kg, SC) in the 4-hour pylorus-ligated rats. The CB1R agonist ( N-arachidonoyl dopamine, 1 mg/kg, SC) inhibited gastric acid secretion stimulated by D-G and carbachol but not in histamine, reduced pepsin content, and increased mucin secretion...
November 1, 2018: Journal of Biochemical and Molecular Toxicology
Min Jee Kim, Motomasa Tanioka, Sun Woo Um, Seong-Karp Hong, Bae Hwan Lee
The insular cortex is an important region of brain involved in the processing of pain and emotion. Recent studies indicate that lesions in the insular cortex induce pain asymbolia and reverse neuropathic pain. Endogenous cannabinoids (endocannabinoids), which have been shown to attenuate pain, are simultaneously degraded by fatty acid amide hydrolase (FAAH) that halts the mechanisms of action. Selective inhibitor URB597 suppresses FAAH activity by conserving endocannabinoids, which reduces pain. The present study examined the analgesic effects of URB597 treatment in the insular cortex of an animal model of neuropathic pain...
January 2018: Molecular Pain
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