Neuronal and astrocytic CB1R signaling differentially modulates goal-directed behavior and working memory by distinct temporal mechanisms

Shang, Huiping; Li, Peijun; Lin, Xiangxiang; Cai, Qionghui; Li, Zhihui; Deng, Lu; Song, Yue; Chen, Jiang‐Fan

doi:10.1038/s41386-023-01533-3

Cited by 4 publications

(4 citation statements)

References 60 publications

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“…In hippocampal neurons, CB1R agonists induce extracellular signal-regulated kinase 1/2 (ERK1/2) activation in a Gi/o-protein-dependent manner, independently of adenylyl cyclase inhibition. This activation of ERK1/2 has been reported in various neuronal cell types, highlighting its physiological relevance in the nervous system [35,36].…”

Section: Cannabinoid Receptor 1 (Cb1r) In Neuroprotection: Mitigating...supporting

confidence: 61%

Neuroprotection and Beyond: The Central Role of CB1 and CB2 Receptors in Stroke Recovery

Bietar,

Tanner,

Lehmann

2023

IJMS

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The endocannabinoid system, with its intricate presence in numerous cells, tissues, and organs, offers a compelling avenue for therapeutic interventions. Central to this system are the cannabinoid receptors 1 and 2 (CB1R and CB2R), whose ubiquity can introduce complexities in targeted treatments due to their wide-ranging physiological influence. Injuries to the central nervous system (CNS), including strokes and traumatic brain injuries, induce localized pro-inflammatory immune responses, termed neuroinflammation. Research has shown that compensatory immunodepression usually follows, and these mechanisms might influence immunity, potentially affecting infection risks in patients. As traditional preventive treatments like antibiotics face challenges, the exploration of immunomodulatory therapies offers a promising alternative. This review delves into the potential neuroprotective roles of the cannabinoid receptors: CB1R’s involvement in mitigating excitotoxicity and CB2R’s dual role in promoting cell survival and anti-inflammatory responses. However, the potential of cannabinoids to reduce neuroinflammation must be weighed against the risk of exacerbating immunodepression. Though the endocannabinoid system promises numerous therapeutic benefits, understanding its multifaceted signaling mechanisms and outcomes remains a challenge.

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Section: Cannabinoid Receptor 1 (Cb1r) In Neuroprotection: Mitigating...supporting

confidence: 61%

Neuroprotection and Beyond: The Central Role of CB1 and CB2 Receptors in Stroke Recovery

Bietar,

Tanner,

Lehmann

2023

IJMS

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“…CB1Rs promote extracellular signal-regulated kinase 1/2 (ERK1/2) activation [ 45 , 46 , 47 ]. This pathway regulates microglia’s inflammatory gene expression and immune responses and has been linked to neuroinflammation and neurodegenerative diseases [ 48 , 49 ].…”

Section: Cannabinoid Receptors and Immunomodulationmentioning

confidence: 99%

“…This contributes to its neuroprotective activity. Indeed, in an in vitro model of HD, activation of CB1Rs protects cells from death, mediated by phosphorylation of ERK [ 46 ].…”

Section: Cannabinoid Receptors and Immunomodulationmentioning

confidence: 99%

Cannabinoids’ Role in Modulating Central and Peripheral Immunity in Neurodegenerative Diseases

Sharon,

Yarmolinsky,

Khalfin

et al. 2024

IJMS

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Cannabinoids (the endocannabinoids, the synthetic cannabinoids, and the phytocannabinoids) are well known for their various pharmacological properties, including neuroprotective and anti-inflammatory features, which are fundamentally important for the treatment of neurodegenerative diseases. The aging of the global population is causing an increase in these diseases that require the development of effective drugs to be even more urgent. Taking into account the unavailability of effective drugs for neurodegenerative diseases, it seems appropriate to consider the role of cannabinoids in the treatment of these diseases. To our knowledge, few reviews are devoted to cannabinoids’ impact on modulating central and peripheral immunity in neurodegenerative diseases. The objective of this review is to provide the best possible information about the cannabinoid receptors and immuno-modulation features, peripheral immune modulation by cannabinoids, cannabinoid-based therapies for the treatment of neurological disorders, and the future development prospects of making cannabinoids versatile tools in the pursuit of effective drugs.

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“…Astrocytes, one of the cell types in the nervous system, are involved several cognitive and brain functions, such as working memory [1][2][3], goal directed behaviors [3,4], control of motor and social behaviors [5,6], regulation of synaptic plasticity [2,7] and neural synchronization [8,9]. As neuron, astrocytes are also active cell, responding to glutamate, dopamine, and noradrenaline released by neurons [8,[10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Diverse Calcium Signaling in Astrocytes: Insights from a Computational Model

Bezerra,

Roque

2024

Preprint

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Astrocytes are complex cells that influence a variety of brain functions and behaviors. They are active cells that show a sharp increase in intracellular Ca2+concentration in response to neurotransmitters (events called Ca2+signals). The main source of intracellular Ca2+is the stores in endoplasmic reticulum (ER), released by the activation of IP3 receptor channels on the ER membrane. As neurons, astrocytes from different brain regions show distinct Ca2+signals. In addition, astrocytes can also show different patterns of Ca2+responses. It is not yet clear how the diversity of astrocyte response emerge from the same mech-anisms. Here we present a two variable astrocyte compartmental model for the Ca2+and IP3 dynamics. We show that Ca2+signals with different characteristics can emerge from changing the parameters associated with the Ca2+and IP3 dynamics and the transmembrane current. We also show that global Ca2+signals are required for the model to trigger different patterns of Ca2+responses. The model present here can be used to simulate astrocytes from different brain regions and with distinct types of response.

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Neuronal and astrocytic CB1R signaling differentially modulates goal-directed behavior and working memory by distinct temporal mechanisms

Cited by 4 publications

References 60 publications

Neuroprotection and Beyond: The Central Role of CB1 and CB2 Receptors in Stroke Recovery

Neuroprotection and Beyond: The Central Role of CB1 and CB2 Receptors in Stroke Recovery

Cannabinoids’ Role in Modulating Central and Peripheral Immunity in Neurodegenerative Diseases

Diverse Calcium Signaling in Astrocytes: Insights from a Computational Model

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