A Role for the Cannabinoid 1 Receptor in Neuronal Differentiation of Adult Spinal Cord Progenitors in vitro is Revealed through Pharmacological Inhibition and Genetic Deletion

Sideris, Alexandra; Bekker, Tatiana; Chan, Wai Si; Montoya-Gacharna, Jose V.; Blanck, Thomas J. J.; Recio-Pinto, Esperanza

doi:10.3389/fnins.2012.00004

Cited by 7 publications

(5 citation statements)

References 52 publications

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“…In the SVZ, NSCs may secrete the endocannabinoid anandamide [32]. The effects of cannabinoids may be dependent on the region from where NPCs are obtained, since NSCs from the spinal cord show neuronal differentiation after genetic or pharmacological inhibition of CB 1 receptors, whereas cannabinoid agonists increase the expression of immature markers such as nestin [33].…”

Section: Cannabinoid Signalling and Neurogenesismentioning

confidence: 99%

Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling

Garcı́a-Ovejero

Arévalo-Martı́n

Navarro-Galve

et al. 2013

Biochemical Society Transactions

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Neuroimmune networks and the brain endocannabinoid system contribute to the maintenance of neurogenesis. Activation of cannabinoid receptors suppresses chronic inflammatory responses through the attenuation of pro-inflammatory mediators. Moreover, the endocannabinoid system directs cell fate specification of NSCs (neural stem cells) in the CNS (central nervous system). The aim of our work is to understand better the relationship between the endocannabinoid and the IL-1β (interleukin-1β) associated signalling pathways and NSC biology, in order to develop therapeutical strategies on CNS diseases that may facilitate brain repair. NSCs express functional CB1 and CB2 cannabinoid receptors, DAGLα (diacylglycerol lipase α) and the NSC markers SOX-2 and nestin. We have investigated the role of CB1 and CB2 cannabinoid receptors in the control of NSC proliferation and in the release of immunomodulators [IL-1β and IL-1Ra (IL-1 receptor antagonist)] that control NSC fate decisions. Pharmacological blockade of CB1 and/or CB2 cannabinoid receptors abolish or decrease NSC proliferation, indicating a critical role for both CB1 and CB2 receptors in the proliferation of NSC via IL-1 signalling pathways. Thus the endocannabinoid system, which has neuroprotective and immunomodulatory actions mediated by IL-1 signalling cascades in the brain, could assist the process of proliferation and differentiation of embryonic or adult NSCs, and this may be of therapeutic interest in the emerging field of brain repair.

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Section: Cannabinoid Signalling and Neurogenesismentioning

confidence: 99%

Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling

Garcı́a-Ovejero

Arévalo-Martı́n

Navarro-Galve

et al. 2013

Biochemical Society Transactions

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“…Interestingly, a recent study indicates that, in vitro, a 4-day treatment of AEA promotes glial differentiation, whereas a 7-day treatment promotes neuronal differentiation [82]. By studying adult spinal cord progenitors in primary cultures and in vitro slices, the knock-down of CB1Rs and treatment with the antagonist AM-251 resulted in enhanced neuronal differentiation [83]. …”

Section: Ecb Signaling Modulates Progenitor Cells Migration and Diffementioning

confidence: 99%

Type-1 Cannabinoid Receptor Signaling in Neuronal Development

Gaffuri

Ladarre

Lenkei³

2012

Pharmacology

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The type-1 cannabinoid receptor (CB1R) was initially identified as the neuronal target of Δ⁹-tetrahydrocannabinol (THC), the major psychoactive substance of marijuana. This receptor is one of the most abundant G-protein-coupled receptors in the adult brain, the target of endocannabinoid ligands and a well-characterized retrograde synaptic regulator. However, CB1Rs are also highly and often transiently expressed in neuronal populations in the embryonic and early postnatal brain, even before the formation of synapses. This suggests important physiological roles for CB1Rs during neuronal development. Several recent reviews have summarized our knowledge about the role of the endocannabinoid (eCB) system in neurodevelopment and neurotransmission by focusing on the metabolism of endocannabinoid molecules. Here, we review current knowledge about the effects of the modulation of CB1R signaling during the different phases of brain development. More precisely, we focus on reports that directly implicate CB1Rs during progenitor cell migration and differentiation, neurite outgrowth, axonal pathfinding and synaptogenesis. Based on theoretical considerations and on the reviewed experimental data, we propose a new model to explain the diversity of experimental findings on eCB signaling on neurite growth and axonal pathfinding. In our model, cell-autonomus and paracrine eCBs acting on CB1Rs are part of a global inhibitory network of cytoskeletal effectors, which act in concert with positive-feedback local-excitation loops, to ultimately yield highly polarized neurons.

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“…Genotypes were confirmed with PCR as previously described. 26 Adult male mice (8–12 weeks old) were used for experiments. Food and water were available ad libitum.…”

Section: Methodsmentioning

confidence: 99%

Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity

et al. 2016

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BackgroundThe function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R−/−) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor.ResultsAt baseline, CB1R−/− mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R−/− mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R−/− mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/−) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R−/− mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different among genotypes.ConclusionCold allodynia and significant recovery from spared-nerve injury-induced mechanical hypersensitivity are two novel phenotypes which characterize the global CB1R−/− mice. An increase in transient receptor potential channel of melastatin 8 channel function in DRG neurons may underlie the cold phenotype. Recovery of mechanical thresholds in the CB1R knockouts was independent of motor function. These results indicate that CB1R expression contributes to the development of persistent mechanical hypersensitivity, protects against the development of robust cold allodynia but is not involved in motor impairment following spared-nerve injury in mice.

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A Role for the Cannabinoid 1 Receptor in Neuronal Differentiation of Adult Spinal Cord Progenitors in vitro is Revealed through Pharmacological Inhibition and Genetic Deletion

Cited by 7 publications

References 52 publications

Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling

Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling

Type-1 Cannabinoid Receptor Signaling in Neuronal Development

Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity

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