Endocannabinoid system and adult neurogenesis: a focused review

Oddi, Sergio; Scipioni, Lucia; Maccarrone, Mauro

doi:10.1016/j.coph.2019.11.002

Cited by 47 publications

(35 citation statements)

References 32 publications

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“…107,108 The role of the ECS in adult neurogenesis is well documented, as reviewed in detail elsewhere. [110][111][112] Experiments performed in mice under home-cage conditions without behavioral challenges revealed that ubiquitous gene deficiency of CB 1 receptor 38 and impaired 2-AG signaling in mice with deficiency of the 2-AG synthesizing enzyme diacylglycerol lipase-α (DAGLα) 113,114 lead to decreased NSC proliferation. On the contrary, under basal conditions, ubiquitous CB 2 receptor deficiency did not lead to impairments in NSC proliferation.…”

Section: Generation Of New Neuronsmentioning

confidence: 99%

“…110 In vitro experiments suggest the involvement of phosphoinositide 3-kinase/protein kinase B (PI3K/PKB), ERK, and mTOR complex 1 (mTORC) pathways in eCB-dependent stimulation of proliferation of NSCs. 110,112,116 For the CB 2 receptor, it has emerged that this receptor is mainly important under pathophysiological conditions, whereby reduction in neurogenesis induced by damaging conditions (epilepsy, alcohol, stroke, neurodegenerative processes) can be alleviated by CB 2 receptor activation. 112 It has to be recognized that the neurogenic niches are embedded into an environment that strongly affects proliferation and that also contains a functional ECS.…”

Section: Neurobiology Of Cannabinoid Receptor Signaling -Lutzmentioning

confidence: 99%

“…110,112,116 For the CB 2 receptor, it has emerged that this receptor is mainly important under pathophysiological conditions, whereby reduction in neurogenesis induced by damaging conditions (epilepsy, alcohol, stroke, neurodegenerative processes) can be alleviated by CB 2 receptor activation. 112 It has to be recognized that the neurogenic niches are embedded into an environment that strongly affects proliferation and that also contains a functional ECS. Therefore, phenotypic outcomes after modulation of ECS activity depend on the cellular and temporal specificity of the targeting of the respective ECS components.…”

Section: Neurobiology Of Cannabinoid Receptor Signaling -Lutzmentioning

confidence: 99%

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Neurobiology of cannabinoid receptor signaling

Lutz

2020

Dialogues in Clinical Neuroscience

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The endocannabinoid system (ECS) is a highly versatile signaling system within the nervous system. Despite its widespread localization, its functions within the context of distinct neural processes are very well discernable and specific. This is remarkable, and the question remains as to how such specificity is achieved. One key player in the ECS is the cannabinoid type 1 receptor (CB1), a G protein–coupled receptor characterized by the complexity of its cell-specific expression, cellular and subcellular localization, and its adaptable regulation of intracellular signaling cascades. CB1 receptors are involved in different synaptic and cellular plasticity processes and in the brain’s bioenergetics in a context-specific manner. CB2 receptors are also important in several processes in neurons, glial cells, and immune cells of the brain. As polymorphisms in ECS components, as well as external impacts such as stress and metabolic challenges, can both lead to dysregulated ECS activity and subsequently to possible neuropsychiatric disorders, pharmacological intervention targeting the ECS is a promising therapeutic approach. Understanding the neurobiology of cannabinoid receptor signaling in depth will aid optimal design of therapeutic interventions, minimizing unwanted side effects.

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Section: Generation Of New Neuronsmentioning

confidence: 99%

Section: Neurobiology Of Cannabinoid Receptor Signaling -Lutzmentioning

confidence: 99%

Section: Neurobiology Of Cannabinoid Receptor Signaling -Lutzmentioning

confidence: 99%

See 1 more Smart Citation

Neurobiology of cannabinoid receptor signaling

Lutz

2020

Dialogues in Clinical Neuroscience

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“…In pathological conditions, where neurogenesis has been found to be disrupted, such as epilepsy, Alzheimer’s, or Parkinson’s Diseases, disturbances associated with ECS homeostasis were also found [ 203 , 237 , 238 , 239 , 240 , 241 ] (reviewed in References [ 113 , 242 , 243 , 244 ]). Thus, it may be proposed that an interplay between the rise of symptomatology of these disorders may be originated from a combined early impairment in neural development or aberrant adult neurogenesis with deficiencies in the ECS.…”

Section: Cannabinoids and The Endocannabinoid Systemmentioning

confidence: 99%

Neural Stem Cells and Cannabinoids in the Spotlight as Potential Therapy for Epilepsy

Lourenço

Ribeiro-Rodrigues

Sebastião

et al. 2020

IJMS

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Epilepsy is one of the most common brain diseases worldwide, having a huge burden in society. The main hallmark of epilepsy is the occurrence of spontaneous recurrent seizures, having a tremendous impact on the lives of the patients and of their relatives. Currently, the therapeutic strategies are mostly based on the use of antiepileptic drugs, and because several types of epilepsies are of unknown origin, a high percentage of patients are resistant to the available pharmacotherapy, continuing to experience seizures overtime. Therefore, the search for new drugs and therapeutic targets is highly important. One key aspect to be targeted is the aberrant adult hippocampal neurogenesis (AHN) derived from Neural Stem Cells (NSCs). Indeed, targeting seizure-induced AHN may reduce recurrent seizures and shed some light on the mechanisms of disease. The endocannabinoid system is a known modulator of AHN, and due to the known endogenous antiepileptic properties, it is an interesting candidate for the generation of new antiepileptic drugs. However, further studies and clinical trials are required to investigate the putative mechanisms by which cannabinoids can be used to treat epilepsy. In this manuscript, we will review how cannabinoid-induced modulation of NSCs may promote neural plasticity and whether these drugs can be used as putative antiepileptic treatment.

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“…In addition, eCBs also play a role in glial cells and in intracellular organelles 5–9 . In the brain, eCBs participate in the short-term and long-term synaptic plasticity of glutamatergic and gamma-aminobutyric acid (GABA)-ergic synapses in a variety of regions, including the cerebral cortex, hippocampus, striatum, ventral tegmental area, amygdala and cerebellum 4,10 , playing an important role in a wide range of physiological processes such as development, emotional state, pain, the sleep/wake cycle, energy metabolism, reward, and learning and memory 11–15 . Given the broad distribution and variety of functions of eCBs, dysregulation of the eCB system has been associated with a plethora of disorders, including neuropsychiatric and neurodegenerative diseases, epilepsy, cancer, and others 16–18 .…”

mentioning

confidence: 99%

A fluorescent sensor for spatiotemporally resolved endocannabinoid dynamicsin vitroandin vivo

Dong

Dudok

et al. 2020

Preprint

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Endocannabinoids (eCBs) are retrograde lipid neuromodulators involved in many physiologically important processes. However, their release and dynamics in the brain remain largely unknown, in part due to lack of probes capable of reporting real-time eCBs with sufficient spatiotemporal resolution. Here, we developed a new G protein-coupled receptor Activation Based eCB sensor GRABeCB2.0 using the human CB1 cannabinoid receptor and a circular-permutated EGFP. GRABeCB2.0 exhibited proper cell membrane trafficking, ~seconds kinetics, high specificity and robust fluorescence response to eCBs at physiological concentrations. Using GRABeCB2.0, we detected evoked eCB dynamics in both cultured neurons and acute brain slices. Interestingly, we also observed spontaneous compartmental eCB transients that spread ~11 μm in cultured neurons, suggesting locally-restricted eCB signaling. By expressing GRABeCB2.0in vivo, we readily observed foot-shock elicited and running triggered eCB transients in mouse amygdala and hippocampus, respectively. Lastly, using GRABeCB2.0 in an epilepsy model, we observed a spreading eCB wave following a calcium wave in mouse hippocampus. In summary, GRABeCB2.0 is a powerful new probe to resolve eCB release and dynamics under both physiological and pathological conditions.

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Endocannabinoid system and adult neurogenesis: a focused review

Cited by 47 publications

References 32 publications

Neurobiology of cannabinoid receptor signaling

Neurobiology of cannabinoid receptor signaling

Neural Stem Cells and Cannabinoids in the Spotlight as Potential Therapy for Epilepsy

A fluorescent sensor for spatiotemporally resolved endocannabinoid dynamicsin vitroandin vivo

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