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endocannabinoid regulates the efficacy of vestibular inhibitory synapses contributing to the expression of gravity-detection behavior in developing rats

Endocannabinoid regulates the efficacy of vestibular inhibit...

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中国神经科学学会第十届全国学术会议

作者： Wei SHI Chun-Wai MA Daisy Kwok-Yan SHUM Ying-Shing CHAN Departments of Physiology Li Ka Shing Faculty of MedicineThe University of Hong Kong Departments of Biochemistry Li Ka Shing Faculty of MedicineThe University of Hong Kong

Long-term depression of inhibitory responses(iLTD),as mediated by endocannabinoid(eCB),plays an important role on presynaptic plasticity in the mammalian ***,the involvement of eCB on the developmental plasticity of the vestibular system remains *** hypothesize that eCB regulates the efficacy of GABAergic synapses in the vestibular nucleus(VN) via the modulation of iLTD,thereby contributing to spatial *** the use of whole-cell patch-clamp experiments,GABA receptor-mediated evoked-IPSCs were recorded on brainstem slice of postnatal *** normal P5-7 rats,iLTD was induced in 70%of the neurons in the medial VN but was reduced to 20%in P8-17 *** proportion of neurons showing iLTD at P5-7 decreased to 40%with bath application of AM251(antagonist of CB1 receptor).Similar results were observed in P5-7 rats pre-implanted at P1 with AM251-loaded Elvax slice that allows slow release of the drug into the underlying *** normal P8-10 rats,the proportion of neurons showing iLTD increased to 60%with bath application of WIN55(agonist of CB1R).Similar results were observed in P8-10 rats pre-implanted at P1 with WIN55-loaded Elvax ***,the proportion decreased to 20%in P11-17 rats pretreated with *** determine the receptor that triggers postsynaptic production and release of eCB we applied to the bath antagonist/agonist of either Group Ⅰmetabotropic glutamate receptor(mGluR) or serotonin receptor(5-HTR).Antagonist/agonist of Group Ⅰ mGluR exerted no effect on iLTD ***,5-HTR agonist increased the proportion of neurons expressing iLTD in P8-10 rats while 5-HTR antagonist decreased the proportion in P5-7 rats,suggesting that 5-HTR is involved in triggering eCB *** investigate the effects of eCB in the expression of vestibular behavior,rats pre-implanted at P1 with AM251- or WIN55-loaded Elvax were tested with negative geotaxis,a behavioral indicator of *** rats acquire the re-orienting beha

关键词： endocannabinoid Long-term depression gravity-detection behavior

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Cannabinoids and endocannabinoids as therapeutics for nervous system disorders:preclinical models and clinical studies

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Neural Regeneration Research 2024年第4期19卷 788-799页

作者： R.Scott Duncan Sean M.Riordan Matthew C.Gernon Peter Koulen Department of Ophthalmology School of MedicineUniversity of Missouri Department of Biomedical Sciences School of MedicineUniversity of Missouri

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human *** have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human *** of these include central nervous system(CNS)diseases and dysfunctions such as forms of epilepsy,multiple sclerosis,Parkinson’s disease,pain and neuropsychiatric *** addition,the endogenously produced cannabinoid lipids,endocannabinoids,are critical for normal CNS function,and if controlled or modified,may represent an additional therapeutic avenue for CNS *** review discusses in vitro cellular,ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS *** addition,the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS *** and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

关键词： anandamide cannabidiol cannabinoid endocannabinoid epilepsy multiple sclerosis neurodegeneration neuroprotection tetrahydrocannabinol

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endocannabinoid-mediated presynaptic plasticity regulates postnatal acquisition of spatial naviga-tion

Endocannabinoid-mediated presynaptic plasticity regulates po...

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中国生理学会第24届全国会员代表大会暨生理学学术大会

作者：陈应诚 Daisy Shum 史微 Denny Ma

Long-term depression of inhibitory responses（LTD）,as mediated by endocannabinoid（e CB）,plays an important role on presynaptic plasticity in the mammalian ***,the involvement of e CB on the developmental plasticity of the vestibular system remains *** the use of whole-cell patch-clamp experiments,GABAA receptor-mediated evoked-IPSCs were recorded on brainstem slice of postnatal *** normal P5-8 rats,LTD was induced in 70%of the neurons in the medial VN but was reduced to 20%in P9-17 *** proportion of neurons showing LTD at P5-8 decreased to 30%with bath application of AM251（antagonist of CB1 receptor）and pre-implanted at P1 with AM251-loaded Elvax *** normal P9-11 rats,the proportion of neurons showing LTD increased to 70%with bath application of WIN55（agonist of CB1R）and pre-implanted at P1 with WIN55-loaded Elvax ***,the proportion decreased to 20%in P12-17 rats pretreated with *** determine the receptor that triggers postsynaptic production and release of e CB we applied to the bath antagonist/agonist of either Group I metabotropic glutamate receptor（m Glu R）or serotonin receptor（5-HTR）.Antagonist/agonist of Group I m Glu R exerted no effect on LTD ***,5-HTR agonist increased the proportion of neurons expressing LTD in P9-11 rats while 5-HTR antagonists decreased the proportion in P5-8 rats,suggesting that 5-HTR is involved in triggering e CB *** investigate the effects of e CB in the expression of vestibular behavior,rats pre-implanted at P1 with AM251-or WIN55-loaded Elvax were tested with negative geotaxis,a behavioral indicator of *** rats acquire the re-orienting behavior by *** emergence of this behavior was accelerated to P5 in AM251-treated rats,but was delayed to P9 in WIN55-treated *** the dead-reckoning test,we found that rats pretreated with WIN55at P1（n=6）showed difficulty in finding their way home（*** in head angle and return time）.However,AM25

关键词： endocannabinoid presynaptic plasticity spatial navigation

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Morinda citrifolia(Noni) Fruit Juice Inhibits endocannabinoid Degradation Enzymes

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Journal of Biosciences and Medicines 2019年第7期7卷 22-34页

作者： Brett J. West Shixin Deng C. Jarakae Jensen Research and Development Morinda Inc. American Fork Utah USA

Morinda citrifolia (noni) fruit juice has been shown to have a wide variety of potential health benefits in human clinical trials. It may also influence the endocannabinoid system of the body. Since the main ingredient of the product studied in these clinical trials was juice made from noni fruit puree from French Polynesia, it was evaluated for its ability to inhibit the two major endocannabinoid degradation enzymes in vitro. Noni fruit juice inhibited both fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) in a concentration-dependent manner, suggesting that it may help maintain anandamide and 2-arachidonoylglycerol levels. Samples of the puree were also analyzed for the presence of characteristic phytochemical markers of authentic noni fruit such as scopoletin, rutin, quercetin, deacetylasperulosidic acid and asperulosidic acid, all of which were present. Also present was scandoside, which is reported for the first time as being identified in noni fruit or its juice. Some of these compounds may contribute to the FAAH and MAGL inhibiting activity of noni juice. These results reveal another set of mechanisms by which noni juice possibly supports mental health, maintains joint health, relieves discomfort and modulates the immune system.

关键词： Morinda citrifolia endocannabinoid System Fatty Acid Amide Hydrolase Monoacylglycerol Lipase

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The endocannabinoid, 2-Arachidonoyl Glycerol, Induces Growth Cone Collapse and Neurite Retraction in Growing Peripheral Sensory Neurons

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World Journal of Neuroscience 2015年第1期5卷 1-6页

作者： Chizu Aso Tomonori Takazawa Tatsuo Horiuchi Shigeru Saito Department of Anesthesiology National Hospital Organization Takasaki General Medical Center Takasaki Japan Department of Anesthesiology Gunma University Graduate School of Medicine Maebashi Japan

Cannabis has a detrimental impact on the developing nervous system. Therefore, regular consumption of cannabis by pregnant and lactating woman poses a potential risk to neuronal growth in fetuses and infants. Indeed, endogenous cannabis-like molecules called endocannabinoids regulate many physiological processes, including neurogenesis, axon guidance, and synaptic plasticity through CB1 receptors. To investigate the physiological role of CB1 receptors on peripheral sensory nerve growth, the endocannabinoid 2-arachidonoyl glycerol was added to cultured chick dorsal root ganglion neurons. This compound inhibited neurite elongation and induced growth cone collapse in a dose- and time-dependent manner. These data suggest that caution should be exercised regarding maternal cannabis use during pregnancy. Because ectopic sprouting and abnormal neuronal network connections are considered to be a cause of neuropathic pain, our current data imply an additional role of endocannabinoids as inhibitors of the formation of pain-maintenance networks.

关键词： endocannabinoid CB1 Receptors Dorsal Root Ganglion Neurons Growth Cone

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Function of the endocannabinoid System in Neurodegenerative Diseases and Cancers

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American Journal of Plant Sciences 2019年第10期10卷 1839-1854页

作者： Mario Soliman Shobha Potlakayala Dhimant Desai Hannah Weeden Rabab Husain Nicole Lookfong Thomas Trite John Spagnola Shantu Amin Sairam Rudrabhatla Burrell College of Osteopathic Medicine Las Cruces NM USA Penn State Harrisburg Middletown PA USA Departments of Pharmacology Pennsylvania State University College of Medicine Hershey PA USA PA Options for Wellness Inc. Harrisburg PA USA.

Neurodegenerative diseases are characterized by progressive degeneration and/or death of neuronal cells and results in a wide array of cognitive impairments and other serious neurological defects. The signaling pathways and definite cause underlying the development of neurodegenerative nerve diseases have not been well defined. There is evidence of mechanisms within the endocannabinoid system that may suggest important pathways involved the progression of neurodegenerative diseases as well as some cancers. The endocannabinoid system is an endogenous ubiquitous neuromodulatory system that plays a critical in the development of the central nervous system (CNS), synaptic plasticity, as well as other primary neuronal functions. The recent identification of various cannabinoid receptors and their endogenous lipid ligands has generated an interest and significant increase in research of the endocannabinoid system and its role in human health and diseases. The endocannabinoid system possesses essential endogenous receptors—cannabinoid receptors type 1 (CB1R) and type 2 (CB2R)—which are involved in mechanisms that contribute to the progression of neurodegenerative diseases and some cancers. In this review, we discuss the role of the endocannabinoid system in various neurodegenerative diseases as well as some cancers, and its promise as a targeted pharmacological therapy for patients of neurodegenerative diseases.

关键词： Cannabinoid endocannabinoid System Neurodegenerative Disorders Cancer

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Differential endocannabinoid production in the hippocampus

Differential endocannabinoid production in the hippocampus

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中国神经科学学会第六届学术会议暨学会成立十周年庆祝大会

作者： David A Edwards Andrew Vila Lawrence J Marnett Bradley E Alger University of Maryland. Baltimore 21201 Vanderbilt University Nashville 37232 Vanderbilt University Nashville 37232 University of Maryland. Baltimore 21201

＜正＞The active ingredient of marijuana is the cannabinoid delta-9-THC. It acts in the CNS by binding to the cannabinoid receptor, CB1. Endogenous cannabinoids （eCBs） are also found in the CNS and bind to the CB1 receptor. Anandamide （AEA） and 2-arachidonyl glycerol （2-AG） are the predominant eCBs in the hippocampus where they are produced and released from the CA1 pyramidal cell, travel in a retrograde direction across the synapse, and bind CB1 on pre-synaptic GABAergic terminals. Activation of CB1 suppresses GABA release and as a result CA1 cells become hyper-excitable and susceptible to long-term plasticity. Several different stimuli can cause the release of eCBs, including depolarization of the CA1 cell, activation of group 1 metabotropic glutamate receptors （mGluRs）, and activation of muscarinic acetylcholine receptors. Suppression of IPSCs can be measured postsynaptically as an assay of eCB activation presynaptically;however, it is not clear what eCB is released by each of these stimuli. We attempted to measure directly the eCB released after treating hippocampal slices with a high concentration of potassium, or the group I selective mGluR agonist, DHPG. The levels of 2-AG or AEA were measured by liquid chromatography and mass spectrometrometry. The two treatments produced different patterns of eCB increase, suggesting that more than one pathway exists for eCB synthesis. This work is supported by USPHS, NIH grants to B.E.A. and L.J.M.

关键词： endocannabinoid hippocampus 2-AG AEA

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Drinking during pregnancy: Potential role of endocannabinoid signaling in fetal alcohol effects

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World Journal of Neurology 2017年第1期7卷 1-5页

作者： Basalingappa L Hungund Nathan Kline Institute for Psy-chiatric Research New York State Psychiatric Institute Department of Psychiatry College of Physicians and Surgeons Columbia University

Alcohol is a well-recognized teratogen that can causevariable physical and behavioral effects on the *** use and abuse during pregnancy is one of the major health and societal problems and has been linked to a wide range of birth defects in the offspring collectively termed as fetal alcohol spectrum disorder(FASD). The severity of abnormalities may depend on a number of factors that include the amount, the frequency, the period during gestation and the route of alcohol administration. The current knowledge about the neurobiological basis of FASD is limited. However, recent studies have suggested that the membrane-derived lipids especially bioactive endogenous cannabinoids(eCB)such as arachidonyl ethanolamide and 2-arachidonyl glycerol resulting from alcohol exposure, may play a significant role in modulating neurophysiological and neurobehavioral effects in chronic alcohol exposed adult animals. Based on these findings and on reported studies on the role of eCB signaling in neurodevelopment and behavior, it is speculated that the eC B signaling may play a critical role in fetal alcohol syndrome and FASD-related behavioral effects. The current discussion will touch upon some of the mechanistic explanations about the role of eCB signaling system in FASD and provide further guidance for future direction.

关键词： Lipid Cannabinoids 1 receptor Alcohol γ-aminobutyric acid endocannabinoid Fetal alcohol spectrum disorder

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Cannabinomimetric Lipids:From Natural Extract to Artificial Synthesis

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Natural Products and Bioprospecting 2018年第1期8卷 1-21页

作者： Ya-Ru Gao Yong-Qiang Wang Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education Department of Chemistry&Materials ScienceNorthwest UniversityXi’an 710069People’s Republic of China

endocannabinoid system is related with various physiological and cognitive processes including fertility,pregnancy,during pre-and postnatal development,pain-sensation,mood,appetite,and *** the latest decades,an important milestone concerning the endocannabinoid system was the discovery of the existence of the cannabinoid receptors CB1 and *** was the first reported endogenous metabolite,which adjusted the release of some neurotransmitters through binding to the CB1 or CB2 *** a series of cannabinomimetric lipids were extracted from marine organisms,which possessed similar structure with *** review will provide a short account about cannabi-nomimetric lipids for their extraction and synthesis.

关键词： endocannabinoid Cannabinoid receptors Cannabinomimetric lipids

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Lignans from Morinda citrifolia(Noni) Fruit Inhibit Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase in Vitro

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Journal of Biosciences and Medicines 2020年第3期8卷 143-152页

作者： Brett J. West Shixin Deng Claude Jarakae Jensen Research and Development New Age Beverages. American Fork Utah USA

Morinda citrifolia (noni) fruit juice has exhibited a variety of biological activities in human clinical trials, indicating that it influences multiple systems of the body. Since the 1990s, the endocannabinoid system (ECS) has been found to modulate the activity of other organ systems. To investigate noni’s potential impact on the ECS, extracts from freeze-dried noni fruit were evaluated in fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition assays. The ethyl acetate extract demonstrated the greatest activity against both enzymes. Lignans in this extract also inhibited enzyme activities, with americanin A being the most active in both assays. Americanoic acid and 3,3’-bisdemethylpinoresinol were the next most active compounds. These results suggest that lignans in noni fruit may influence endocannabinoid levels within the body via FAAH and MAGL inhibition. This reveals another set of probable mechanisms of action by which noni juice affects human health.

关键词： Morinda citrifolia Noni endocannabinoid System Fatty Acid Amide Hydrolase Monoacylglycerol Lipase

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