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1.
Microglia are the resident immune cells of the brain, and they are under permanent activity to patrol the cerebral microenvironment. A proper inhibitory feedback onto these cells is critical during both intact and injury conditions. In this issue of Neuron, Eljaschewitsch and colleagues report that such feedback is provided by the endogenous cannabinoid anandamine and CB(1/2) receptor signaling, which ultimately leads to mitogen-activated protein kinase phosphatase-1 (MKP-1) induction. MKP-1 interferes with lipopolysaccharide-induced toll-like receptor 4 signaling and limits brain damage due to exaggerated microglial reactivity following acute NMDA injury. 相似文献
2.
Velasco G Carracedo A Blázquez C Lorente M Aguado T Haro A Sánchez C Galve-Roperh I Guzmán M 《Molecular neurobiology》2007,36(1):60-67
Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances—the endocannabinoids—that activate specific cell surface receptors.
Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different
types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways,
mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor
cells and the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds, as they
kill glioma cells, but not their non-transformed astroglial counterparts. On the basis of these preclinical findings, a pilot
clinical study of Δ9-tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has been recently run. The good safety profile
of THC, together with its possible growth-inhibiting action on tumor cells, justifies the setting up of future trials aimed
at evaluating the potential antitumoral activity of cannabinoids. 相似文献
3.
Gardiner SM Bennett T 《American journal of physiology. Heart and circulatory physiology》2005,288(1):H451; author reply H451-H451; author reply H452
4.
Pertwee RG 《Molecular neurobiology》2007,36(1):45-59
This review discusses clinical and preclinical evidence that supports the use of cannabinoid receptor agonists for the management
of multiple sclerosis. In addition, it considers preclinical findings that suggest that as well as ameliorating signs and
symptoms of multiple sclerosis, cannabinoid CB1 and/or CB2 receptor activation may suppress some of the pathological changes that give rise to these signs and symptoms. Evidence that
the endocannabinoid system plays a protective role in multiple sclerosis is also discussed as are potential pharmacological
strategies for enhancing such protection in the clinic. 相似文献
5.
Cannabinoid system is a crucial mechanism in regulating food intake and energy metabolism. It is involved in central and peripheral
mechanisms regulating such behavior, interacting with many other signaling systems with a role in metabolic regulation. Cannabinoid
agonists promote food intake, and soon a cannabinoid antagonist, rimonabant, will be marketed for the treatment of obesity.
It not only causes weight loss, but also alleviates metabolic syndrome. We present a review of current knowledge on this subject,
along with data from our own research: genetic studies on this system in eating disorders and obesity and studies locating
cannabinoid receptors in areas related to food intake. Such studies suggest cannabinoid hyperactivity in obesity, and this
excessive activity may have prognostic implications. 相似文献
6.
Steven P Cohen 《BMJ (Clinical research ed.)》2008,336(7637):167-168
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The discovery of endocannabinoids such as anandamide and the wide spread localization of cannabinoid receptors in the brain and peripheral tissues, suggests that the cannabinoid system represents a previously unrecognized ubiquitous net work in the nervous system, whose physiology and function is unfolding. In this study, we tested the hypothesis that some of the actions of anandamide are independent of a cannabinoid receptor mechanism. This was accomplished by the use of cannabinoid agonist and antagonist interaction in an in-vitro and in-vivo test systems. In-vitro, we used Xenopus laevis oocytes expression system and two-voltage clamp technique in combination with differential display polymerase chain reaction to determine whether the differential display of genes following treatment with anandamide may be linked to AMPA glutamate receptor. The differential expression of genes in vivo after the sub-acute administration of anandamide could not be directly linked with the AMPA glutamate receptor. In the voltage clamp studies we investigated the effects of anandamide on recombinant AMPA GluR3 sub-unit currents generated by kainic acid in oocytes expressing the AMPA glutamate receptor. In the in-vitro studies, we present evidence that anandamide inhibited the kainate activated currents in oocytes expressing AMPA glutamate receptor involves cAMP transduction via a cannabinoid receptor independent mechanism. In the in-vivo studies, SR141716A, the CB1 antagonist, induced anxiolysis, that was dependent on the mouse strain used in the anxiety model and blocked the anxiogenic effects of anandamide or methanandamide whereas SR141716A had no effect on the anandamide inhibition of kainate activated currents in-vitro. 相似文献
9.
NOS knockouts and neuroprotection 总被引:2,自引:0,他引:2
10.
Mitochondria play a key function in cellular metabolism. Additionally to ATP synthesis, mitochondria may buffor cytosolic calcium ions and generate reactive oxygen species. Due to these processes, mitochondria are involved in complex cytoprotective phenomena. Neuroprotection is very often based on changes in the integrity of mitochondrial membranes. In this report potential neuroprotective role of mitochondrial ion channels is discussed. 相似文献
11.
Cannabinoids, hippocampal function and memory. 总被引:12,自引:0,他引:12
Prior studies from this laboratory have shown that the psychoactive ingredient in marijuana, delta9-tetrahydrocannabinol (THC), interferes with short-term memory (1-3) in both delayed match and nonmatch to sample tasks (DMS/DNMS). Recent experiments have shown that other cannabinoids such as the potent CB1 receptor agonist, WIN 55,212-2 produces a delay-dependent deficit in the DNMS task at a dose range (0.10-0.50 mg/kg) well below that of delta9-THC which was blocked by the CB11 receptor antagonist SR141716A (Sanofi Inc). The effects of WIN 55,212-2 at low doses were similar to those of isolated lesions of the hippocampus, whereas high doses (0.50 mg/kg, i.p.) produced effects similar to lesions of both hippocampus and surrounding retrohippocampal areas. The low dose effect was delay-dependent while the high dose introduced an additional deficit at short delays that was sensitive to both SR141716A and the GABA(B) receptor antagonist, phaclofen. Comparison of lesion vs. cannabinoid effects on DNMS performance suggests that CB1 receptors on hippocampal neurons interfere with the processing of DNMS task-specific information within a trial. CB1 receptors on hippocampal GABAergic interneurons and in retrohippocampal areas appear to influence the ability to maintain segregation of information between trials in the task. 相似文献
12.
Sagredo O García-Arencibia M de Lago E Finetti S Decio A Fernández-Ruiz J 《Molecular neurobiology》2007,36(1):82-91
Cannabinoids have been proposed as clinically promising neuroprotective molecules, as they are capable to reduce excitotoxicity,
calcium influx, and oxidative injury. They are also able to decrease inflammation by acting on glial processes that regulate
neuronal survival and to restore blood supply to injured area by reducing the vasoconstriction produced by several endothelium-derived
factors. Through one or more of these processes, cannabinoids may provide neuroprotection in different neurodegenerative disorders
including Parkinson’s disease and Huntington’s chorea, two chronic diseases that are originated as a consequence of the degeneration
of specific nuclei of basal ganglia, resulting in a deterioration of the control of movement. Both diseases have been still
scarcely explored at the clinical level for a possible application of cannabinoids to delay the progressive degeneration of
the basal ganglia. However, the preclinical evidence seems to be solid and promising. There are two key mechanisms involved
in the neuroprotection by cannabinoids in experimental models of these two disorders: first, a cannabinoid receptor-independent
mechanism aimed at producing a decrease in the oxidative injury and second, an induction/upregulation of cannabinoid CB2 receptors,
mainly in reactive microglia, that is capable to regulate the influence of these glial cells on neuronal homeostasis. Considering
the relevance of these preclinical data and the lack of efficient neuroprotective strategies in both disorders, we urge the
development of further studies that allow that the promising expectatives generated for these molecules progress from the
present preclinical evidence till a real clinical application. 相似文献
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Cannabinoids and brain injury: therapeutic implications 总被引:6,自引:0,他引:6
Mounting in vitro and in vivo data suggest that the endocannabinoids anandamide and 2-arachidonoyl glycerol, as well as some plant and synthetic cannabinoids, have neuroprotective effects following brain injury. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission and reduce the production of tumour necrosis factor-alpha and reactive oxygen intermediates, which are factors in causing neuronal damage. The formation of the endocannabinoids anandamide and 2-arachidonoyl glycerol is strongly enhanced after brain injury, and there is evidence that these compounds reduce the secondary damage incurred. Some plant and synthetic cannabinoids, which do not bind to the cannabinoid receptors, have also been shown to be neuroprotective, possibly through their direct effect on the excitatory glutamate system and/or as antioxidants. 相似文献
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Cannabinoids, the active components of Cannabis sativa (marijuana) and their endogenous counterparts, exert their effects by binding to specific G-protein-coupled receptors that modulate adenylyl cyclase and ion channels. Recent research has shown that the CB1 cannabinoid receptor is also coupled to the generation of the lipid second messenger ceramide via two different pathways: sphingomyelin hydrolysis and ceramide synthesis de novo. Sustained ceramide accumulation in tumor cells mediates cannabinoid-induced apoptosis, as evidenced by in vitro and in vivo studies. This effect seems to be due to the impact of ceramide on key cell signalling systems such as the extracellular signal-regulated kinase cascade and the Akt pathway. These findings provide a new conceptual view on how cannabinoids act, and raise interesting physiological and therapeutic questions. 相似文献
17.
E Pop 《Current opinion in chemical biology》1999,3(4):418-425
The investigation of natural and synthetic cannabinoid ligands, including (-)-Delta(9)-tetrahydrocannabinol, cannabinol, cannabidiol, HU-210, HU-211, CT3, CP 55, 940, WIN 55, 212-2, SR 14, 1716A, anandamide, 2-arachidonoylglycerol, and numerous novel analogs, has led to important findings that have contributed to a better understanding of the role of these compounds in physiological processes. Their potential use for medicinal purposes is also better understood as a result. 相似文献
18.
Alsasua del Valle A 《Cellular and molecular neurobiology》2006,26(4-6):577-589
SUMMARY 1. Preparations from Cannabis sativa (marijuana) have been used for many centuries both medicinally and recreationally.2. Recent advances in the knowledge of its pharmacological and chemical properties in the organism, mainly due to Δ9-tetrahydrocannabinol, and the physiological roles played by the endocannabinoids have opened up new strategies in the treatment of neurological and psychiatric diseases.3. Potential therapeutic uses of cannabinoid receptor agonists include the management of spasticity and tremor in multiple sclerosis/spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, cancer, and vasodilation that accompanies advanced cirrhosis. CB1 receptor antagonists have therapeutic potential in Parkinson's disease.4. Dr. Julius Axelrod also contributed in studies on the neuroprotective actions of cannabinoids. 相似文献
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20.
Cannabinoids as potential new analgesics. 总被引:4,自引:0,他引:4
Among other pharmacological properties analgesia is one of the important features of cannabinoids with therapeutical prospects. Cannabinoids have been shown to produce antinociception in experimental animals and humans. Recently a new system of neuromodulation based upon the existence of cannabinoid receptors and their endogenous agonists has emerged. This has been proposed as another of the endogenous pain control systems. Current evidence indicate an interaction between cannabinoid and opioid systems, the latter being of known relevance in nociception. The fact that either exogenous or endogenous opioids enhanced cannabinoid-induced antinociception suggests simultaneous activation of both opioid and cannabinoid receptors by drugs as a new analgesic strategy. 相似文献