Cannabinoid receptor 2 activation mitigates lipopolysaccharide-induced neuroinflammation and sickness behavior in mice

Sahu, Puspita; Mudgal, Jayesh; Arora, Devinder; Kinra, Manas; Mallik, Sanchari Basu; Chamallamudi, Mallikarjuna Rao; Pai, K. S. R.; Nampoothiri, Madhavan

doi:10.1007/s00213-019-5166-y

Cited by 42 publications

(20 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CB 2 receptor agonism has been shown to decrease brain levels of pro-inflammatory cytokines induced by LPS application [ 187 ], intracerebral hemorrhages [ 188 ], or surgery [ 189 ] as well as in a model of PD [ 190 ]. At the same time the CB 1 receptor inverse agonist SR141716A (rimonabant) and the CB 2 receptor antagonist SR144528 significantly reduced LPS-induced IL-1β production in the brain [ 191 ] whereas SR141716A was also shown to increase pro-inflammatory cytokines in an EAE model [ 192 ].…”

Section: Neuroinflammation-induced Synaptopathy and Neurodegenerative Diseasesmentioning

confidence: 99%

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

Kasatkina

Rittchen

Sturm

2021

IJMS

View full text Add to dashboard Cite

Endocannabinoids (eCBs) are lipid-based retrograde messengers with a relatively short half-life that are produced endogenously and, upon binding to the primary cannabinoid receptors CB1/2, mediate multiple mechanisms of intercellular communication within the body. Endocannabinoid signaling is implicated in brain development, memory formation, learning, mood, anxiety, depression, feeding behavior, analgesia, and drug addiction. It is now recognized that the endocannabinoid system mediates not only neuronal communications but also governs the crosstalk between neurons, glia, and immune cells, and thus represents an important player within the neuroimmune interface. Generation of primary endocannabinoids is accompanied by the production of their congeners, the N-acylethanolamines (NAEs), which together with N-acylneurotransmitters, lipoamino acids and primary fatty acid amides comprise expanded endocannabinoid/endovanilloid signaling systems. Most of these compounds do not bind CB1/2, but signal via several other pathways involving the transient receptor potential cation channel subfamily V member 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)-α and non-cannabinoid G-protein coupled receptors (GPRs) to mediate anti-inflammatory, immunomodulatory and neuroprotective activities. In vivo generation of the cannabinoid compounds is triggered by physiological and pathological stimuli and, specifically in the brain, mediates fine regulation of synaptic strength, neuroprotection, and resolution of neuroinflammation. Here, we review the role of the endocannabinoid system in intrinsic neuroprotective mechanisms and its therapeutic potential for the treatment of neuroinflammation and associated synaptopathy.

show abstract

Section: Neuroinflammation-induced Synaptopathy and Neurodegenerative Diseasesmentioning

confidence: 99%

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

Kasatkina

Rittchen

Sturm

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In the antigen-presenting cells (APC), HCQ inhibits the antigen processing and presentation of autoantigen mediated by the major histocompatibility complex (MHC) class II to T cells. Due to this, the levels of activated T cells decline, causing a reduction in the production of cytokines generated by T cells and the B cells [46,47]. The changes in pH caused by HCQ also affects the toll-like receptor (TLR) functioning.…”

Section: Inhibition Through Prevention Of Cytokine Stormmentioning

confidence: 99%

Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2

et al. 2020

Self Cite

View full text Add to dashboard Cite

Purpose of Review The rapid spread of virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has turned out to be a global emergency. Symptoms of this viral infection, coronavirus disease 2019 (COVID-19), include mild infections of the upper respiratory tract, viral pneumonia, respiratory failure, multiple organ failure and death. Till date, no drugs have been discovered to treat COVID-19 patients, and therefore, a considerable amount of interest has been shown in repurposing the existing drugs. Recent Findings Out of these drugs, chloroquine (CQ) and hydroxychloroquine (HCQ) have demonstrated positive results indicating a potential antiviral role against SARS-CoV-2. Its mechanism of action (MOA) includes the interference in the endocytic pathway, blockade of sialic acid receptors, restriction of pH mediated spike (S) protein cleavage at the angiotensin-converting enzyme 2 (ACE2) binding site and prevention of cytokine storm. Unfortunately, its adverse effects like gastrointestinal complications, retinopathy and QT interval prolongation are evident in treated COVID-19 patients. Yet, multiple clinical trials have been employed in several countries to evaluate its ability in turning into a needed drug in this pandemic. Summary This review attempts to summarize the MOA of CQ/HCQ and its side effects. The existing literature hints that till date, the role of CQ/HCQ in COVID-19 may be sceptical, and further studies are warranted for obtaining a therapeutic option that could be effectively used across the world to rise out from this pandemic.

show abstract

“…Cannabinoids, both endogenous and exogenous, have been demonstrated to have anti-inflammatory, anti-oxidant, and neuroprotective effects in the CNS [ 309 , 310 , 311 , 312 , 313 ]. Glial cells, both astrocytes and microglia, are well-known to have potent immunomodulatory roles in the brain [ 314 , 315 , 316 ].…”

Section: Biological Role Of the Cannabinoid Receptorsmentioning

confidence: 99%

Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

Haspula

Clark

2020

IJMS

View full text Add to dashboard Cite

The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

show abstract

Cannabinoid receptor 2 activation mitigates lipopolysaccharide-induced neuroinflammation and sickness behavior in mice

Cited by 42 publications

References 34 publications

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2

Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

Contact Info

Product

Resources

About