Tag Archives: endocannabinoid system

Endocannabinoids drive the acquisition of an alternative phenotype in microglia.

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“The ability of microglia to acquire diverse states of activation, or phenotypes, reflects different features that are determinant for their contribution to homeostasis in the adult CNS, and their activity in neuroinflammation, repair or immunomodulation.

Despite the widely reported immunomodulatory effects of cannabinoids in both the peripheral immune system and the CNS, less is known about how the endocannabinoid signaling system (eCBSS) influence the microglial phenotype.

The general aim of the present study was to investigate the role of endocannabinoids in microglia polarization by using microglia cell cultures.

We show that alternative microglia (M2a) and acquired deactivated microglia (M2c) exhibit changes in the eCB machinery that favor the selective synthesis of 2-AG and AEA, respectively.

Once released, these eCBs might be able to act through CB1 and/or CB2 receptors in order to influence the acquisition of an M2 phenotype.

We present three lines of evidence that the eCBSS is critical for the acquisition of the M2 phenotype: (i) M2 polarization occurs on exposure to the two main endocannabinoids 2-AG and AEA in microglia cultures; (ii)cannabinoid receptor antagonists block M2 polarization; and, (iii) M2 polarization is dampened in microglia from CB2 receptor knockout mice.

Taken together, these results indicate the interest of eCBSS for the regulation of microglial activation in normal and pathological conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/26086345

Role of the Endocannabinoid System in Diabetes and Diabetic Complications.

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“Increasing evidence suggests that an overactive endocannabinoid system (ECS) may contribute to the development of diabetes by promoting energy intake and storage, impairing both glucose and lipid metabolism, and by exerting pro-apoptotic effects in pancreatic β cells, and by facilitating inflammation in pancreatic islets.

Furthermore, hyperglycemia associated with diabetes has also been implicated in triggering perturbations of the ECS amplifying the above mentioned pathological processes, eventually culminating in a vicious circle.

Compelling evidence from preclinical studies indicates that the ECS also influences diabetes-induced oxidative stress, inflammation, fibrosis, and subsequent tissue injury in target organs for diabetic complications.

In this review, we provide an update on the contribution of the ECS to the pathogenesis of diabetes and diabetic microvascular (retinopathy, nephropathy, and neuropathy) and cardiovascular complications. The therapeutic potential of targeting the ECS is also discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/26076890#

http://www.thctotalhealthcare.com/category/diabetes/

Neurobiological Interactions Between Stress and the Endocannabinoid System.

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“Stress affects a constellation of physiological systems in the body and evokes a rapid shift in many neurobehavioral processes.

A growing body of work indicates that the endocannabinoid (eCB) system is an integral regulator of the stress response.

In the current review, we discuss the evidence to date that demonstrates stress-induced regulation of eCB signaling and the consequential role changes in eCB signaling play with respect to many of the effects of stress.

Across a wide array of stress paradigms, studies have generally shown that stress evokes bidirectional changes in the two eCB molecules, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), with stress exposure reducing AEA levels and increasing 2-AG levels.

Additionally, in almost every brain region examined, exposure to chronic stress reliably causes a down-regulation or loss of cannabinoid type 1 (CB1) receptors.

With respect to the functional role of changes in eCB signaling during stress, studies have demonstrated that the decline in AEA appears to contribute to the manifestation of the stress response, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and increases in anxiety behavior, while the increased 2-AG signaling contributes to termination and adaptation of the HPA axis, as well as potentially contributing to changes in pain perception and synaptic plasticity.

More so, translational studies have shown that eCB signaling in humans regulates many of the same domains and appears to be a critical component of stress regulation, and impairments in this system may be involved in the vulnerability to stress-related psychiatric conditions, such as depression and post-traumatic stress disorder.

Collectively, these data create a compelling argument that eCB signaling is an important regulatory system in the brain that largely functions to buffer against many of the effects of stress and that dynamic changes in this system contribute to different aspects of the stress response.”

http://www.ncbi.nlm.nih.gov/pubmed/26068727

In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe.

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“Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases…

Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care.

The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe…

The combined evidence indicates that NIR760-mbc94 is a promising inflammation imaging probe. Moreover, in vivo CB2R-targeted fluorescence imaging may have potential in the study of inflammation-related diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26069858

Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain.

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“The levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol.

In this study, we investigated the role of the endocannabinoid system (ECS) in the emotional and cognitive alterations associated with osteoarthritis pain.

Changes found in these biomarkers of the ECS correlated with pain, affective and cognitive symptoms in these patients.

The ECS plays a crucial role in osteoarthritis and represents an interesting pharmacological target and biomarker of this disease.”

http://www.ncbi.nlm.nih.gov/pubmed/26067584

http://www.thctotalhealthcare.com/category/osteoarthritis/

New horizons for newborn brain protection: enhancing endogenous neuroprotection.

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“Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE).

The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised.

Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear.

It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.

There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE.

In this review, we focus on strategies that can augment the body’s own endogenous neuroprotection.

We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult.

Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential.

Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade.”

http://www.ncbi.nlm.nih.gov/pubmed/26063194

[Over-expression of cannabinoid receptor 2 induces the apoptosis of cervical carcinoma Caski cells].

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“Objective: To construct a eukaryotic expression vector containing human cannabinoid receptor 2 (hCB2R) gene and investigate its expression, location and the influence on the apoptosis of cervical cancer Caski cells.

Conclusion: The up-regulated expression of hCB2R could induce cell apoptosis by enhancing the expressions of Bax, Bad and suppressing the expression of Bcl-2 in Caski cells.”

http://www.ncbi.nlm.nih.gov/pubmed/26062417

http://www.thctotalhealthcare.com/category/cervical-cancer/

Medical Marijuana in Pediatric Neurological Disorders.

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“Marijuana and marijuana-based products have been used to treat medical disease.

Recently, derivatives of the plant have been separated or synthesized to treat various neurological disorders, many of them affecting children.

Unfortunately, data are sparse in regard to treating children with neurologic illness. Therefore, formal conclusions about the potential efficacy, benefit, and adverse effects for these products cannot be made at this time.

Further robust research using strong scientific methodology is desperately needed to formally evaluate the role of these products in children.”

http://www.ncbi.nlm.nih.gov/pubmed/26060306

“The endocannabinoid-CB receptor system: Importance for development and in pediatric disease.”  http://www.ncbi.nlm.nih.gov/pubmed/15159678

Localization of an endocannabinoid system in the hypophysial pars tuberalis and pars distalis of man.

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“The hypophysial pars tuberalis (PT) acts as an important interface between neuroendocrine brain centers (hypothalamus, pineal organ) and the pars distalis (PD) of the hypophysis.

Recently, we have identified an endocannabinoid system in the PT of hamsters and provided evidence that 2-arachidonoylglycerol is a messenger molecule that appears to play an essential role in seasonal reproduction and prolactin release by acting on the cannabinoid receptors in the PD.”

“An endocannabinoid system is localized to the hypophysial pars tuberalis of Syrian hamsters and responds to photoperiodic changes.”  http://www.ncbi.nlm.nih.gov/pubmed/20165884

“We now demonstrate the enzymes involved in endocannabinoid synthesis and degradation, namely sn-1-selective diacylglycerol lipase α, N-acylphosphatidylethanolamine-specific phospholipase D, and monoacylglycerol lipase, in the PT of man by means of immunohistochemistry.

High-performance liquid chromatography coupled with tandem mass spectrometry revealed 2-arachidonoylglycerol and other endocannabinoids in the human PT.

Furthermore, we detected the expression of the cannabinoid receptor 1 (CB1), a primary receptor for endocannabinoids, in the PD.

Our data thus indicate that the human PT comprises an endocannabinoid system, and that corticotrophs and FS-cells are the main target cells for endocannabinoids.

The functional significance of this newly discovered pathway remains to be elucidated in man; it might be related to the control of stress responses and/or reflect a remnant seasonal control of hypophysial hormonal secretion.”

http://www.ncbi.nlm.nih.gov/pubmed/20957495

The rat pineal gland comprises an endocannabinoid system.

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“In the mammalian pineal gland, the rhythm in melatonin biosynthesis depends on the norepinephrine (NE)-driven regulation of arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme of melatonin biosynthesis.

A recent study showed that phytocannabinoids like tetrahydrocannabinol reduce AANAT activity and attenuate NE-induced melatonin biosynthesis in rat pineal glands, raising the possibility that an endocannabinoid system is present in the pineal gland…

In summary, the pineal gland comprises indispensable compounds of the endocannabinoid system indicating that endocannabinoids may be involved in the control of pineal physiology.”

http://www.ncbi.nlm.nih.gov/pubmed/18554250