Regulation of a Neuronal Form of Focal Adhesion Kinase by Anandamide

Derkinderen, Pascal; Toutant, Madeleine; Burgaya, Ferràn; Bert, Marc Le; Siciliano, Julio C.; Franciscis, Vittorio de; Gelman, Michèle; Girault, Jean‐Antoine

doi:10.1126/science.273.5282.1719

Cited by 169 publications

(166 citation statements)

References 27 publications

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“…Cannabinoids regulate gap-junction permeability, thereby controlling intercellular communication in astrocytes as well as neuron-glial interaction, for example by preventing the recruitment of subpopulations of astrocytes and the subsequent activation of contacting groups of neurons (Venance et al 1995). In addition, regulation of a neuronal form of focal adhesion kinase by cannabinoids has been described, indicating that these compounds play a role in synaptic plasticity (Derkinderen et al 1996).…”

Section: Resultsmentioning

confidence: 99%

Specific attentional dysfunction in adults following early start of cannabis use

et al. 1999

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Rationale and objective:The present study tested the hypothesis that chronic interference by cannabis with endogenous cannabinoid systems during peripubertal development causes specific and persistent brain alterations in humans. As an index of cannabinoid action, visual scanning, along with other attentional functions, was chosen. Visual scanning undergoes a major maturation process around age 12-15 years and, in addition, the visual system is known to react specifically and sensitively to cannabinoids. Methods: From 250 individuals consuming cannabis regularly, 99 healthy pure cannabis users were selected. They were free of any other past or present drug abuse, or history of neuropsychiatric disease. After an interview, physical examination, analysis of routine laboratory parameters, plasma / urine analyses for drugs, and MMPI testing, users and respective controls were subjected to a computer-assisted attention test battery comprising visual scanning, alertness, divided attention, flexibility, and working memory. Results: Of the potential predictors of test performance within the user group, including present age, age of onset of cannabis use, degree of acute intoxication (THC+THCOH plasma levels), and cumulative toxicity (estimated total life dose), an early age of onset turned out to be the only predictor, predicting impaired reaction times exclusively in visual scanning. Early-onset users (onset before age 16; n = 48) showed a significant impairment in reaction times in this function, whereas late-onset users (onset after age 16; n = 51) did not differ from controls (n = 49). Conclusions: These data suggest that beginning cannabis use during early adolescence may lead to enduring effects on specific attentional functions in adulthood. Apparently, vulnerable periods during brain development exist that are subject to persistent alterations by interfering exogenous cannabinoids.

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Section: Resultsmentioning

confidence: 99%

Specific attentional dysfunction in adults following early start of cannabis use

et al. 1999

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“…Thus, the phosphorylation of focal adhesion kinase (FAK) was modulated by THC and the endocannabinoids AEA and 2-AG in a CB1R-dependent manner [114,115]. Interestingly, FAK is critically involved in the regulation of integrins and their association with the actin cytoskeleton, a key regulator of synaptic plasticity [116].…”

Section: (D) Cellular and Subcellular Localization Of Cb1r And Its Immentioning

confidence: 99%

Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids

Puighermanal

Busquets-García

Maldonado

et al. 2012

Phil. Trans. R. Soc. B

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Exogenous cannabinoids, such as delta9-tetrahydrocannabinol (THC), as well as the modulation of endogenous cannabinoids, affect cognitive function through the activation of cannabinoid receptors. Indeed, these compounds modulate a number of signalling pathways critically implicated in the deleterious effect of cannabinoids on learning and memory. Thus, the involvement of the mammalian target of rapamycin pathway and extracellular signal-regulated kinases, together with their consequent regulation of cellular processes such as protein translation, play a critical role in the amnesic-like effects of cannabinoids. In this study, we summarize the cellular and molecular mechanisms reported in the modulation of cognitive function by the endocannabinoid system.

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“…In various non-neuronal cells, cAMP prevents the activation of ERK by mitogens, whereas in neuronal cells such as PC12, an increase in the intracellular concentration of cAMP activates the ERK pathway. Because we had demonstrated previously that cAMP was involved in the effects of endocannabinoids on protein tyrosine phosphorylation in hippocampal slices (Derkinderen et al, 1996(Derkinderen et al, , 2001b, we examined its role in ERK regulation. We treated hippocampal slices with 8-Bromo (Br)-cAMP, a cell-permeant analog of cAMP, or forskolin, a stimulator of adenylyl cyclase, for different periods of time.…”

Section: Role Of Camp In the Control Of Erk Activation By Cannabinoidmentioning

confidence: 99%

“…Intraperitoneal injection of cannabinoid agonists increases the expression of IEGs, products including Zif268, c-Fos, and c-Jun, in rat forebrain (Mailleux et al, 1994;Glass and Dragunow, 1995), but the mechanism of these responses is not known. We have shown previously that cannabinoids augment tyrosine phosphorylation of the neuronal splice isoform of focal adhesion kinase (FAK) (Derkinderen et al, 1996(Derkinderen et al, , 2001bBurgaya et al, 1997) and its association with the Src family tyrosine kinase Fyn (Derkinderen et al, 2001b). Cannabinoids also activate p38-MAPK, but not c-Jun N-terminal kinase, in hippocampal slices (Derkinderen et al, 2001a).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Extracellular Signal-Regulated Kinase by Cannabinoids in Hippocampus

et al. 2003

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Endocannabinoids form a novel class of intercellular messengers, the functions of which include retrograde signaling in the brain and mediation or modulation of several types of synaptic plasticity. Yet, the signaling mechanisms and long-term effects of the stimulation of CB1 cannabinoid receptors (CB1-R) are poorly understood. We show that anandamide, 2-arachidonoyl-glycerol, and ⌬9-tetrahydrocannabinol (THC) activated extracellular signal-regulated kinase (ERK) in hippocampal slices. In living mice, THC activated ERK in hippocampal neurons and induced its accumulation in the nuclei of pyramidal cells in CA1 and CA3. Both effects were attributable to stimulation of CB1-R and activation of MAP kinase/ERK kinase (MEK). In hippocampal slices, the stimulation of ERK was independent of phosphatidyl-inositol-3-kinase but was regulated by cAMP. The endocannabinoid-induced stimulation of ERK was lost in Fyn knockout mice, in slices and in vivo, although it was insensitive to inhibitors of Src-family tyrosine kinases in vitro, suggesting a noncatalytic role of Fyn. Finally, the effects of cannabinoids on ERK activation were dependent on the activity of glutamate NMDA receptors in vivo, but not in hippocampal slices, indicating the existence of several pathways linking CB1-R to the ERK cascade. In vivo THC induced the expression of immediate-early genes products (c-Fos protein, Zif268, and BDNF mRNAs), and this induction was prevented by an inhibitor of MEK. The strong potential of cannabinoids for inducing long-term alterations in hippocampal neurons through the activation of the ERK pathway may be important for the physiological control of synaptic plasticity and for the general effects of THC in the context of drug abuse.

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Regulation of a Neuronal Form of Focal Adhesion Kinase by Anandamide

Cited by 169 publications

References 27 publications

Specific attentional dysfunction in adults following early start of cannabis use

Specific attentional dysfunction in adults following early start of cannabis use

Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids

Regulation of Extracellular Signal-Regulated Kinase by Cannabinoids in Hippocampus

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