Microglial Cells as a Link between Cannabinoids and the Immune Hypothesis of Psychiatric Disorders

Lisboa, Sabrina F.; Gomes, Felipe V.; Guimarães, Francisco Silveira; Campos, Alline C.

doi:10.3389/fneur.2016.00005

Cited by 55 publications

(39 citation statements)

References 141 publications

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“…Indeed, microglial cells are cells of immunity at the cerebral level, and their link with psychiatric manifestations have already been established (Lisboa et al . ).…”

Section: Discussionmentioning

confidence: 97%

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Cannabidiol affects circadian clock core complex and its regulation in microglia cells

et al. 2018

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Cannabis is often used by consumers for sleep disorders. Studies show that circadian rhythm could be affected by a misuse of cannabis. Recent research has connected the role of microglial cells with psychiatric disorders such as substance abuse. The aim was to show the effect of two major components of cannabis on circadian genes regulation in microglial cells. In BV-2 microglial cells, cannabidiol (CBD) induces a deregulation of circadian genes with (P-value = 0.039) or without (P-value = 0.0015) lipopolisaccharides stimulation. CBD up regulated Arntl (P = 9.72E-5) and down regulated Clock (P = 0.0034) in BV-2 cells. Temporal expression of Arntl (light and dark P = 0.0054) and Clock (light and dark P = 0.047) was confirmed to have 24 hours light and dark rhythmic regulation in dissected suprachiasmatic nucleus as well as of Cb1 cannabinoid receptor (light and dark P = 0.019). In BV-2 microglia cells, CBD also up regulated CRY2 (P = 0.0473) and PER1 (P = 0.0131). Other nuclear molecules show a deregulation of circadian rhythm in microglial cells by CBD, such as RORA, RevErbα, RORB, CREBBP, AFT4, AFT5 and NFIL3. Our study suggests that circadian rhythm in microglial cells is deregulated by CBD but not by THC. It is consistent with clinical observations of the use of therapeutic cannabis to treat insomnia.

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“…Indeed, microglial cells are cells of immunity at the cerebral level, and their link with psychiatric manifestations have already been established (Lisboa et al . ).…”

Section: Discussionmentioning

confidence: 97%

“…Moreover, it is known that the endocannabinoid system may be sensitive to changes in the physiology of the microglial cell (Lisboa et al . ). Indeed, during microglial activation, by a stress or an inflammatory state, the CB2 receptors are more expressed (Walter et al .…”

Section: Introductionmentioning

confidence: 97%

Cannabidiol affects circadian clock core complex and its regulation in microglia cells

et al. 2018

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“…It is suggested that some similar brain pathology may be shared by the two psychiatric disorders. In the past decades, a body of literature has supported the implication of immune alterations in MDD and schizophrenia 35. Our previous work indicated that CFH plays a major role in the development of MDD 14.…”

Section: Discussionmentioning

confidence: 97%

Influence of <em>CFH</em> gene on symptom severity of schizophrenia

Zhang¹,

Lv²,

Fan³

et al. 2017

NDT

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ObjectiveRecent advances have provided compelling evidence for the role of excessive complement activity in the pathophysiology of schizophrenia. In this study, we aimed to detect the association of the gene encoding complement factor H (CFH), a regulator in complement activation, with schizophrenia.Materials and methodsA sample of 1783 individuals with or without schizophrenia was recruited for genetic analysis. Genomic DNA samples were extracted from peripheral blood cells using multiplex polymerase chain reaction and the SNaPshot assay. A Database for Schizophrenia Genetic Research (SZDB) was used to detect the association of brain CFH expression with schizophrenia. Next, we performed a genotype–phenotype analysis to identify the relationship between CFH Y402H polymorphism and clinical features of schizophrenia.ResultsThere was a significant association of hippocampal CFH expression with schizophrenia (P=0.017), whereas this significance did not survive after adjusting for false discovery rate (P=0.105). Comparing the genotype and allele frequencies of the genotyped single-nucleotide polymorphisms between case and control groups showed no significant difference. There were significant differences in the scores of negative symptoms and delayed memory between the patients with C allele and those without C allele (P<0.01 and P=0.04 after Bonferroni correction, respectively). Furthermore, we observed a marginally significant association between the Y402H polymorphism and CFH expression in the hippocampus (P=0.051); however, this significance was lost after multiple testing correction (P=0.51, after Bonferroni correction).ConclusionOur findings provide suggestive evidence for the role of CFH in the development of negative symptoms and cognitive dysfunction in schizophrenia.

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“…It is well known that the endocannabinoid system is an important neuromodulatory system that mediates a broad range of physiological processes [ 1 , 2 ]. Endogenous cannabinoids and its receptors can regulate some biological processes, such as nervous system development, immune homeostasis, and the response to multiple endogenous and environmental insults.…”

Section: Introductionmentioning

confidence: 99%

Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats

Niu

Huang

Zhou

et al. 2017

J Neuroinflammation

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BackgroundMore evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats.MethodsChronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain. The paw withdrawal latency (PWL) was used to evaluate thermal hyperalgesia in neuropathic rats. The expression of P2Y12 and P2Y13 receptors, p-p38MAPK, and NF-kappaBp65 was detected with RT-PCR and western blotting analysis.ResultsTreatment with AM1241 produces a pronounced inhibition of CCI-induced thermal hyperalgesia and significantly inhibited the increased expression of P2Y12 and P2Y13 receptors at the mRNA and protein levels, which open up the possibility that P2Y12 and P2Y13 receptor expression are downregulated by CB2 receptor agonist AM1241 in CCI rats. Western blot analysis demonstrated that AM1241 reduced the elevated expression of p-p38MAPK and NF-κBp65 in the dorsal spinal cord induced by CCI. After administration with either SB203580 (p38MAPK inhibitor) or PDTC (NF-kappaB inhibitor), the levels of P2Y13 receptor expression in the dorsal spinal cord were lower than those in the CCI group. However, in CCI rats, the increased expression of P2Y12 receptor was prevented by intrathecal administration of PDTC but not by SB203580. In addition, minocycline significantly decreased the increased expression of P2Y12 and P2Y13 receptors. The similar results can be observed in ADPbetaS-treated rats. Intrathecal injection of ADPbataS causes thermal hyperalgesia and increased expression of P2Y12 and P2Y13 receptors in the dorsal spinal cord of naive rats. Moreover, intrathecal injection of AM1241 alleviates pain response and reduces the elevated expression of P2Y12 and P2Y13 receptors, p-p38MAPK, and NF-κBp65 in the dorsal spinal cord of ADPbetaS-treated rats. Intrathecal injection of SB203580 significantly inhibited the ADPbetaS-induced P2Y13 receptor expression, without affecting P2Y12 receptor expression. However, treatment with either SB203580 or PDTC effectively inhibited P2Y13 receptor expression compared to ADPbetaS-treated rats.ConclusionsIn CCI- and ADPbetaS-treated rats, AM1241 pretreatment could efficiently activate CB2 receptor, while inhibiting p38MAPK and NF-kappaB activation in the dorsal spinal cord. CB2 receptor stimulation decreased P2Y13 receptor expression via p38MAPK/NF-kappaB signaling. On the other hand, CB2 receptor activation decreased P2Y12 receptor expression via p38MAPK-independent NF-kappaB signaling pathway.

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Microglial Cells as a Link between Cannabinoids and the Immune Hypothesis of Psychiatric Disorders

Cited by 55 publications

References 141 publications

Cannabidiol affects circadian clock core complex and its regulation in microglia cells

Cannabidiol affects circadian clock core complex and its regulation in microglia cells

Influence of <em>CFH</em> gene on symptom severity of schizophrenia

Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats

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