Tiziana Bisogno

Tiziana Bisogno
Italian National Research Council | CNR · Endocannabinoid Research Group, Istituto di Chimica Biomolecolare,

About

174
Publications
20,870
Reads
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22,865
Citations
Additional affiliations
November 2018 - present
Italian National Research Council
Position
  • Researcher
January 2013 - January 2019
Università Campus Bio-Medico di Roma
Position
  • Professor
March 1995 - November 2018
Italian National Research Council
Position
  • Researcher

Publications

Publications (174)
Article
Full-text available
In this study, a novel approach was developed to quantify endocannabinoids (eCBs), and was based on the liquid biosensor BIONOTE. This device is composed of a probe that can be immersed in a solution, and an electronic interface that can record a current related to the oxy-reductive reactions occurring in the sample. The two most representative mem...
Article
Full-text available
Although the primordial concept of lipids is associated with the role they play as key components of the cell membrane, growing research in the field of bioactive lipids and lipidomic technologies proves the prominent role of these molecules in other biological functions [...]
Article
Increased circulating sclerostin and accumulation of advanced glycation end‐products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Whether the expression of the sclerostin‐encoding SOST gene is altered in T2D, and whether it is associated with AGEs accumulation or regulation o...
Article
Full-text available
The lipid signal is becoming increasingly crowded as increasingly fatty acid amide derivatives are being identified and considered relevant therapeutic targets. The identification of N-arachidonoyl-ethanolamine as endogenous ligand of cannabinoid type-1 and type-2 receptors as well as the development of different –omics technologies have the merit...
Article
Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from act...
Article
Full-text available
There is robust evidence indicating that enhancing the endocannabinoid (eCB) tone has therapeutic potential in several brain disorders. The inhibition of eCBs degradation by fatty acid amide hydrolase (FAAH) blockade, is the best-known option to increase N-acyl-ethanolamines-(NAEs)-mediated signaling. Here, we investigated the hypothesis that intra...
Article
Objective: Despite the growing knowledge on the functional relationship between an altered endocannabinoid (eCB) system and development of anorexia nervosa (AN), to date no studies have investigated the central eCB tone in the activity-based anorexia (ABA) model that reproduces key aspects of human AN. Method: We measured levels of two major eCB...
Article
Full-text available
In the present work, mice overexpressing mutant amyloid precursor protein (Tg2576), a transgenic model of Alzheimer's disease, were used to investigate a specific lipid profile over the course of disease progression. Using a targeted a lipidomic approach, we measured plasma levels of N‐acylethanolamines with different length and unsaturation at pre...
Article
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Growing evidence suggests that endocannabinoid levels are modulated during pathological conditions affecting both central and peripheral nervous system. In the present study, a novel approach (patent pending) based on an innovative liquid biosensor has been used to analyze two relevant endocannabinoid molecules with calibration purposes: N-arachido...
Article
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Objective: Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and its pathogenesis has not yet been completely clarified. Patients with SLE show a deranged lipid metabolism, which can contribute to the immunopathogenesis of the disease and to the accelerated atherosclerosis. Resolvin D1 (RvD1), a product of the metabolism of the...
Article
The endocannabinoid (eCB) system plays a key role in many physiological and pathological conditions and its dysregulation has been described in several rheumatological and autoimmune diseases. Yet, its possible alteration in systemic lupus erythematosus (SLE) has never been investigated. Here, we aimed filling this gap in plasma and peripheral bloo...
Article
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Emerging evidence suggest an impaired endocannabinoid activity in the pathophysiology of binge eating disorder (BED). Herein, we investigated whether endocannabinoid tone could be modified as a consequence of dietary-induced binge eating in female rats. For this purpose, brain levels of the endocannabinoids anandamide (AEA) and 2-arachidonoyl glyce...
Article
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Significance: Under physiological conditions, neurons and glia are in a healthy, redox-balanced environment; when injury perturbs this equilibrium, a neuroinflammatory state is established by activated microglia that triggers pro-inflammatory responses and alters the oxidant/antioxidant balance, thus leading to neuronal loss and neurodegeneration....
Article
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Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet, and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system app...
Article
Evidence has been produced that macrophages can actively generate endocannabinoids (eCBs) in response to inflammatory stimuli. As eCBs are involved in the control of several physiological processes, including reproduction, here, we explored whether seminal levels of the eCBs, N-arachidonoylethanolamine (AEA), and 2-arachidonoylglycerol (2-AG), were...
Presentation
29th ECNP Congress, 17-20 September 2016, Vienna (Austria). S.12: Junior Scientist symposium ─ Emerging targets for improved control of psychiatric disorders Fixed symposia, scheduled in the translational research track. Eight speakers selected from the poster presenters at the ECNP Workshop for Junior Scientists in Europe, 17-20 March 2016, Nice (...
Article
Introduction: psychoactive substances are associated with the idea of drugs with high addictive liability, affecting mental states, cognition, emotion and motor behavior. However these substances can modify synaptic transmission and help to disclose some mechanisms underlying alterations in brain processing and pathophysiology of motor disease. Hen...
Article
Based on its wide expression in immune cells, type 2 cannabinoid (CB2) receptors were traditionally thought to act as “peripheral receptors” with an almost exclusively immunomodulatory function. However, their recent identification in mammalian brain areas, as well as in distinct neuronal cells, has opened the way to a re-consideration of CB2 signa...
Chapter
The endocannabinoid 2-arachidonoylglycerol (2-AG) exerts its physiological action by binding to and functionally activating type-1 (CB1) and type-2 (CB2) cannabinoid receptors. It is thought to be produced through the action of sn-1 selective diacylglycerol lipase (DAGL) that catalyzes 2-AG biosynthesis from sn-2-arachidonate-containing diacylglyce...
Article
Background Endocannabinoid (eCB) system comprises endogenous lipid mediators (eCBs) like N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), along with their specific G protein-coupled type-1 (CB1) and type-2 (CB2) cannabinoid receptors, and the proteins responsible for eCB biosynthesis, inactivation, transport, and accu...
Article
Full-text available
Diet plays a central role in maintaining health throughout life and a controlled food intake is associated to a reduced risk of certain diseases. A proper diet should include vitamins, minerals, carbohydrates, proteins, and fats that have to be optimally balanced in order to exert their physiological functions. The endogenous ligands of type-1 and...
Article
Full-text available
The cannabinoid CB2 receptor, which is activated by the endocannabinoid 2-arachidonoyl-glycerol (2-AG), protects striatal neurons from apoptotic death caused by the local administration of malonate, a rat model of Huntington's disease (HD). In the present study, we investigated whether endocannabinoids provide tonic neuroprotection in this HD model...
Chapter
The two most studied endocannabinoids (eCB) are anandamide and 2-arachidonoyl-glycerol (2-AG), for which metabolic routes and enzymes were identified. CB1 receptors are often expressed on presynaptic axon terminals in the brain and participate in the retrograde control of neurotransmitter release and of both short- and long-term synaptic plasticity...
Article
Background: It has been previously shown that CB1 cannabinoid receptor agonism using cannabis extracts alleviates spasticity in both a mouse experimental autoimmune encephalomyelitis (EAE) model and multiple sclerosis (MS) in humans. However, this action can be associated with dose-limiting side effects. Objective: We hypothesised that blockade...
Article
Full-text available
Introduction: Fatty acid amide hydrolase (FAAH) is the major catabolic enzyme of the endocannabinoid N-arachidonoylethanolamine (anandamide) that, with different degrees of efficiency, also hydrolyzes other endogenous fatty acid ethanolamides. FAAH is increasingly being considered a relevant therapeutic target, especially in models of inflammatory...
Article
Background and purpose: The development of potent and selective inhibitors of the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) via DAG lipases (DAGL) α and β is just starting to be considered as a novel and promising source of pharmaceuticals for the treatment of disorders that might benefit from a reduction in endocannabinoid...
Article
Dipyrone is a common antipyretic drug and the most popular non-opioid analgesic in many countries. In spite of its long and widespread use, molecular details of its fate in the body are not fully known. We administered dipyrone orally to mice. Two unknown metabolites were found, viz. the arachidonoyl amides of the known major dipyrone metabolites,...
Article
Full-text available
Omega-3 polyunsaturated fatty acids (ω-3-PUFA) are known to ameliorate several metabolic risk factors for cardiovascular disease, and an association between elevated peripheral levels of endogenous ligands of cannabinoid receptors (endocannabinoids) and the metabolic syndrome has been reported. We investigated the dose-dependent effects of dietary...
Article
Full-text available
The identity and subcellular sources of endocannabinoids (eCBs) will shape their ability to affect synaptic transmission and, ultimately, behavior. Recent discoveries support the conclusion that 2-arachidonoyl glycerol, 2-AG, is the major signaling eCB, however, some important issues remain open. 2-AG can be synthesized by a mechanism that is stric...
Article
Cannabidiol (CBD) and Δ(9) -tetrahydrocannabinol (THC) interact with transient receptor potential (TRP) channels and enzymes of the endocannabinoid system. The effects of 11 pure cannabinoids and botanical extracts [botanical drug substance (BDS)] from Cannabis varieties selected to contain a more abundant cannabinoid, on TRPV1, TRPV2, TRPM8, TRPA1...
Article
In agreement with the highly lipophilic nature of (-)-delta9-tetrahydrocannabinol, all the endogenous ligands of cannabinoid receptors identified so far are derivatives of long chain fatty acids. N- Arachidonoylethanolamine (anandamide) and some of its polyunsaturated congeners have been found in mammalian brain and shown to activate the CB1 and, w...
Article
Full-text available
The G-protein coupled receptors for Δ⁹-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB₁) and 2 (CB₂) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB₁ receptors are mostly expressed in neurons, where they regulate ne...
Article
Evidence suggests that dietary long chain polyunsaturated fatty acids (LCPUFAs), and particularly those belonging to the n-3 family, may influence the brain fatty acid profile and, thereby, the biosynthesis of endocannabinoids in rodents. However, the doses used are usually quite high and not comparable with human intake. Recently, we have shown th...
Article
Full-text available
Endocannabinoids control hippocampal inhibitory synaptic transmission through activation of presynaptic CB(1) receptors. During depolarization-induced suppression of inhibition (DSI), endocannabinoids are synthesized upon postsynaptic depolarization. The endocannabinoid 2-arachidonoylglycerol (2-AG) may mediate hippocampal DSI. Currently, the best...
Article
N-Acylethanolamines, including N-palmitoyl-ethanolamine (PEA), are hydrolyzed to the corresponding fatty acids and ethanolamine by fatty acid amide hydrolase (FAAH). Recently, N-acylethanolamine-hydrolyzing acid amidase (NAAA) was identified as being able to specifically hydrolyze PEA. In order to find selective and effective inhibitors of this enz...
Article
Full-text available
Palmitoylethanolamide (PEA) is an anti-inflammatory mediator that enhances the activation by anandamide (AEA) of cannabinoid receptors and transient receptor potential vanilloid type-1 (TRPV1) channels, and directly activates peroxisome proliferator-activated receptor-alpha (PPAR-alpha). In mice, 2,4-dinitrofluorobenzene (DNFB)-induced contact alle...
Article
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During transit through the epididymis, spermatozoa are normally kept immotile and do not attain the ability to become motile until they reach the caudal epididymis. This study was undertaken to determine whether endocannabinoids play a role in the epididymis and in particular in suppressing the ability of spermatozoa to become motile. We show that...
Article
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The exact role of the endocannabinoid system (ECS) during spermatogenesis has not been clarified. We used purified germ cell fractions representative of all phases of spermatogenesis and primary cultures of spermatogonia. This approach allowed the precise quantification of the cannabinoid receptor ligands, anandamide and 2-arachidonoylglycerol, and...
Article
Full-text available
Dietary (n-3) long-chain PUFA [(n-3) LCPUFA] ameliorate several metabolic risk factors for cardiovascular diseases, although the mechanisms of these beneficial effects are not fully understood. In this study, we compared the effects of dietary (n-3) LCPUFA, in the form of either fish oil (FO) or krill oil (KO) balanced for eicosapentaenoic acid (EP...
Article
N-arachidonoyl dopamine (NADA) is an endogenous ligand that activates the cannabinoid type 1 receptor and the transient receptor potential vanilloid type 1 channel. Two potential biosynthetic pathways for NADA have been proposed, though no conclusive evidence exists for either. The first is the direct conjugation of arachidonic acid with dopamine a...
Article
Biosynthesis Inhibition: O-5596, a new inhibitor of the biosynthesis of the endocannabinoid, 2-arachidonoylglycerol, was synthesized and found to be potent (IC(50)=100 nM) and selective versus other proteins and enzymes of the endocannabinoid system in vitro and active in vivo at reducing food intake in mice.
Article
We have studied the effect of cannabinoid agonists (CP 55,940 and cannabinol) on intestinal motility in a model of intestinal inflammation (induced by oral croton oil in mice) and measured cannabinoid receptor expression, endocannabinoids (anandamide and 2-arachidonylglycerol) and anandamide amidohydrolase activity both in physiological and pathoph...
Article
The identification of the endogenous ligands of the cannabinoid CB1 and CB2 receptors (endocannabinoids) as lipids nominally derived from arachidonic acid was a further demonstration that lipid molecules can be endowed with important signaling functions. This discovery was paralleled by the development of ever more sophisticated technologies for th...
Article
Full-text available
In the CNS, endocannabinoids are identified mainly as two endogenous lipids: anandamide, the ethanolamide of arachidonic acid, and 2-arachidonoylglycerol (2-AG). Endocannabinoids are known to inhibit transmitter release from presynaptic terminals; however we have recently demonstrated that they are also involved in slow self-inhibition (SSI) of lay...
Article
Full-text available
The fungal pathogen Candida albicans transforms arachidonic acid (AA) into 3-hydroxyarachidonic acid [3R-HETE], and we investigated if its nonpathogenic and 3R-HETE-producing close relative, Dipodascopsis uninucleata, could similarly transform the endocannabinoid/endovanilloid anandamide into 3-hydroxyanandamide (3-HAEA). We found that D. uninuclea...
Article
Although inhibitors of the enzymatic hydrolysis of the endocannabinoid 2-arachidonoylglycerol are available, they are either rather weak in vitro (IC(50)>30 microM) or their selectivity towards other proteins of the endocannabinoid system has not been tested. Here we describe the synthesis and activity in vitro and in vivo of a tetrahydrolipstatin...
Article
A series of 21 analogues of tetrahydrolipstatin (THL, 1) were synthesized and tested as inhibitors of the formation or hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Three of the novel compounds, i.e., 11, 13, and 15, inhibited 2-AG formation via the diacylglycerol lipase alpha (DAGLalpha) with IC 50 values lower than 50 nM (IC 50...
Article
Endocannabinoids are lipid mediators with protective effects in many diseases of the nervous system. We have studied the modulation of the endocannabinoid system after a spinal cord contusion in rats. In early stages, lesion induced increases of anandamide and palmitoylethanolamide (PEA) levels, an upregulation of the synthesizing enzyme NAPE-phosp...
Article
In the present study, 11 novel N-(3,3-diphenyl)propyl-2,2-diphenylacetamide derivatives (4a-d and 9a-g) and six triphenylacetamides (10a-c and 11a-c) were synthesized and tested as ligands of cannabinoid CB(1) and CB(2) receptors. All compounds exhibited affinity for CB(1) and CB(2) receptors. Four compounds (4b, 9a, 9b, and 11a) showed selectivity...
Article
The finding of specific binding sites for Delta(9)-tetrahydrocannabinol, the psychoactive component of Cannabis sativa, has led to the discovery of the endocannabinoid system and has emphasised the physiological and pathological relevance of endocannabidoid lipid signalling. Subsequently, an increasing number of papers have been published on the bi...
Article
Full-text available
Unlike other neuroinflammatory disorders, like Parkinson's disease, Huntington's disease and multiple sclerosis, little is still known of the role of the endocannabinoid system in Alzheimer's disease (AD). This is partly due to the poor availability of animal models that are really relevant to the human disease, and to the complexity of AD as compa...
Article
Previous studies have shown an impairment of the endocannabinoid system in experimental models of Huntington's disease. In transgenic R6/2 mice, created by inserting exon 1 of the human IT15 mutant gene into the mouse, and exhibiting 150 CAG repeats as well as signs of HD, a progressive decline of CB(1) receptor expression and an abnormal sensitivi...
Article
Full-text available
In this study, we investigated the mechanism of S100B neurotoxicity and the effect of cannabinoids, in C6 cells treated with 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) and co-cultured with differentiated PC12 cells. MPTP concentration- and time-dependently increased S100B density in C6 cells. This effect was followed by increased C6 cell p...
Article
The activity of the endocannabinoid system, in terms of the levels of the endocannabinoids and of cannabinoid receptors, or of the functional coupling of the latter to a biological response, undergoes to remodelling during pathological conditions. In the CNS, these changes, depending also on the nature of the disorder, can be transient or long-last...
Article
Biphenylic ester derivatives, designed by using a 'soft-drug' approach, proved to possess good binding properties toward cannabinoid CB(1) and CB(2) receptors and, at the same time, their metabolically labile ester portion would promote a rapid systemic inactivation. This may constitute a possible solution to the psychotropic side effects encounter...
Article
In our ongoing program aimed at the design, synthesis, and biological evaluation of novel cannabinoid receptor ligands derived from olivetol and hexyl-resorcinol, we have designed a structural model for new derivatives on the basis of a previous study. Here we report the synthesis, binding, and molecular modeling studies of new potent compounds wit...
Article
Cannabis sativa has been known, used, and misused by mankind for centuries, and yet only over the last two decades has research stemming from the chemical constituents specific to this plant, the cannabinoids, started to provide fundamental insights into animal physiology and pathology, resulting in the development of new therapeutics. The discover...
Article
Recent studies have shown that activation of the cannabinoid CB(1) receptor by synthetic agonists, and pharmacological elevation of endocannabinoid levels, suppress hyperalgesia and allodynia in animal models of neuropathic pain. However, the concentrations of endocannabinoids in the nervous tissues involved in pain transmission during neuropathic...
Article
Endocannabinoids acting on CB(1) cannabinoid receptors are involved in short- and long-term depression of synaptic transmission. The aim of the present study was to determine which endocannabinoid, anandamide or 2-arachidonoylglycerol (2-AG), is involved in depolarization-induced suppression of inhibition (DSI) in the cerebellar cortex, which is th...
Article
We have previously reported the development of CB-25 and CB-52, two ligands of CB1 and CB2 cannabinoid receptors. We assessed here their functional activity. The effect of the two compounds on forskolin-induced cAMP formation in intact cells or GTP-gamma-S binding to cell membranes, and their action on nociception in vivo was determined. CB-25 enha...
Article
Endocannabinoids act as neuroprotective molecules promptly released in response to pathological stimuli. Hence, they may represent one component of protection and/or repair mechanisms mobilized by dopamine (DA) neurons under ischemia. Here, we show that the endocannabinoid 2-arachidonoyl-glycerol (2-AG) plays a key role in protecting DA neurons fro...
Article
Full-text available
The interplay between fear expression and fear extinction provides an important prerequisite for adequate coping with aversive encounters. Current models propose that extinction of conditioned fear is mediated by associative safety learning. Here, we demonstrate that the cannabinoid CB1 receptor, which is crucially involved in fear extinction, is d...
Article
Full-text available
Endocannabinoids were first defined in 1995 as 'endogenous substances capable of binding to and functionally activating the cannabinoid receptors'. To date, two well-established endocannabinoids, N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), as well as a few other putative ligands, all derived from long-chain polyunsatu...