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ObjectiveTo investigate the mechanism of Akkermansia muciniphila （A. muciniphila） regulating the visceral hypersensitivity in irritable bowel syndrome （IBS） rats induced by neonatal maternal separation （MS） and water avoidance stress （WAS）. MethodsNeonatal male Sprague-Dawley rats were randomly divided into sham WAS group （blank group）， MS+WAS group （IBS model group） and A. muciniphila group. IBS model was established by MS combined with WAS in both IBS model group and A. muciniphila group. Meanwhile， the rats in the A. muciniphila group were given 1 mL 1×109 CFU/mL A. muciniphila by gavage daily for 10 days. Visceral pain responses were detected by behavioral observations and abdominal withdrawal reflex scores. ResultsCompared with IBS model group， A. muciniphila group exhibited significant increase of body weight and visceral pain threshold， significantly decreased numbers of fecal particles and proportions of unformed stools， significantly higher expression levels of cannabinoid receptor type 2 （CB2R） mRNA in colon tissues. ConclusionA. muciniphila may alleviate the visceral hypersensitivity in IBS rats by regulating the expression of CB2R mRNA in colonic tissues.
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Cannabinoid receptor type 2( CB2 R),a member of the G protein-coupled receptor( GPCR) superfamily,has a variety of biological activities,such as regulating pain response,resisting inflammation and fibrosis,and mediating bone metabolism. Some CB2 R regulators exhibit a good regulatory effect on bone metabolism. Cannabinoids in Cannabis sativa can cause psychoactive effects despite various pharmacological actions they exerted by targeting CB2 R. Therefore,it is of great significance to discover CB2 R regulators in non-Cannabis plants for finding new lead compounds without psychoactive effects and elucidating the action mechanism of plant drugs. The present study clarifies the discovery,structure,and physiological functions of CB2 R,especially its regulatory effects on bone metabolism,summarized CB2 R regulators extracted from non-Cannabis plants,and systematically analyzes the regulatory effects of CB2 R regulators on bone metabolism in animals,osteoblasts,and osteoclasts,to provide a scientific basis for the discovery of new CB2 R regulators and the development of anti-osteoporotic drugs.
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Animals , Cannabinoids/pharmacology , Cannabis , Osteoblasts , Osteoclasts , Receptors, CannabinoidABSTRACT
BACKGROUND: Astrocyte proliferation is an important morphological change in epilepsy. Proliferated glial cells can produce cytokines, and in turn activates JAK/STAT signal transduction to promote glial cell proliferation, which affects the occurrence and recurrence of epilepsy. Astrocytes and signal transduction pathways interact with each other to play a role in the pathogenesis of epilepsy. OBJECTIVE: To investigate the effect of cannabinoid receptor type 2 (CB2R) on the activation of ERK, p38, and JNK proteins in astrocytes and MAPK pathways in juvenile rats with persistent epilepsy. METHODS: Forty healthy male Sprague-Dawley rats (18-21 days old) were randomly divided into four groups: normal control group, epilepsy model group, CB2R agonist JWH133 group, CB2R antagonist AM630 group. The normal control group was given only normal saline. In the other groups, rats were intraperitoneally injected with lithium chloride and pilocarpine to establish epilepsy models, and different interventions were performed. Twenty-four hours after the onset of epilepsy, brain tissues were taken. Co-expression of GFAP and p-ERK, p-p38, and p-JNK in hippocampal tissue was detected by immunofluorescence. Real-time PCR was used to detect the expression of GFAP mRNA in hippocampal tissue. RESULTS AND CONCLUSION: The co-expression of GFAP/p-ERK and GFAP/p-p38 was significantly higher in the epilepsy model group than the normal control group (P < 0.05), significantly lower in the JWH133 group than the epilepsy model group (P < 0.05), and significantly higher in the AM630 group than the JWH133 group (P < 0.05). The co-expression of GFAP/p-JNK was significantly lower in the epilepsy model group than in normal control group (P < 0.05), significantly higher in the JWH133 group than the epilepsy model group (P < 0.05), and significantly lower in the AM630 group than the JWH133 group (P < 0.05). The mRNA expression of GFAP was significantly decreased in the epilepsy model group compared with the normal control group (P < 0.05), significantly increased in the JWH133 group compared with the epilepsy model group (P < 0.05), and significantly reduced in the AM630 group compared with the JWH133 group (P < 0.05). Therefore, CB2R can regulate the expression of ERK, p38, JNK proteins in the MAPK pathway, thereby affecting astrocytes in the hippocampus of juvenile rats with persistent epilepsy.
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Objective To explore effect of cannabinoid receptor type 2(CB2R)on the expression of autophagy-related proteins LC3 and Beclin-1 in the hippocampal CA1 region of rats with status epilepticus ( SE). Methods SE model was established by treating lithium chloride-pilocarpine intraperitoneally injection in Sprague-Dawley(SD) rats. All the rats were randomly divided into four groups including Control group, Epilepsy group,Epilepsy + JWH-133 group and Epilepsy + AM630 group. JWH-133, AM630, and DMSO were injected 60 min before pilocarpine injection by intracerebroventricular injection ( Control group and Epilepsy group with DMSO,Epilepsy+JWH-133 group with JWH-133 and Epilepsy+AM630 group with AM630). At 24 h after SE,the epileptic symptoms were observed. HE staining was performed to observe the number changes of neurons in the hippocampal CA1 region. The spatiotemporal expressions of LC3 and Beclin-1 in the hippocampal CA1 region were observed using Double-label immunofluorescence and Western blot. Results Epileptic symptoms showed that rats in the control group had no obvious epileptic seizures. Those in Epilepsy group presented seizures about (13. 50 ± 0. 61)min after treated with pilocarpine and racine scale was (4. 33 ± 0. 47) scores. The latency period in Epilepsy+JWH-133 group was(19. 33 ± 0. 42) min and longer than that in the Epilepsy group(P<0. 05);Racine scale in Epilepsy+JWH-133 group was 3. 33 ± 0. 59 and less than the Epilepsy group( P<0. 05). The opposite effect was observed in Epilepsy+AM630 group. HE staining showed that compared with the Epilepsy group,the number of the hippocampal CA1 neu-rons increased in Epilepsy+JWH-133 group and decreased in Epilepsy+AM630 group. Immunofluorescence and Western blot showed that LC3 and Beclin-1 were mainly expressed in neurons,and the expression of LC3 and Beclin-1 in Epilepsy group were up-regulated dynamically than that in the control group at 24 h after SE (P<0. 05). Furthermore compared with the Epilepsy group,the expression of LC3 and Beclin-1 in Epilepsy+JWH-133 group were higher but lowered in Epilepsy+AM630 group. Conclusion We demonstrate that CB2R may play a role in autophagy of the hippocampal neurons at the early stage of pilocarpine-induced SE and hinted CB2R may become a treatment target for epilepsy.
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Objective The expression and correlation between cannabinoid receptor type 2 ( CB2R) and autophagy-related protein microtubule-associated protein 1 light chain 3 (LC3) in the hippocampal CA1 re-gion of developing rats with status epilepticus ( SE) were investigated. Methods SE model was established u-sing lithium chloride-pilocarpine intraperitoneally in Sprague-Dawley ( SD) rats and all the rats were randomly divided into four groups ( control group and 3h, 24h, 3d groups after SE). The expressions of CB2R and LC3 in the hippocampal CA1 region at different times were observed using double-label immunofluorescence and Western blotting. Spearman correlational analysis was used to compare the relationship between the two factors. Results Immunofluorescence showed that the expression of CB2R was up-regulated dynamically and peaked at 24h and presented parabolic changes over time. The expression of LC3 changed in accordance with CB2R and e-ven co-expressed with CB2R partly, especially on neurons. Western blotting results furtherly showed the simi-larity of the expression of CB2R and LC3, and finally Spearman correlational analysis presented the significant correlation between these two factors (r=0. 7161, P<0. 05). Conclusion Significant correlation exists be-tween the expression of CB2R and LC3 in the hippocampal CA1 neurons of developing rats with SE, indicating the essential role of CB2R in autophagy regulation of hippocampal CA1 neurons.
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The endocannabinoid system is composed of endocannabinoids,enzymes for the biosynthesis and degradation of endocannabinoids,and specific cannabinoid receptors (cannabinoid receptor type 1,CB1R;cannabinoid receptor type 2,CB2R).The previous view is that CB1Rs are mainly expressed in the central neurons,whereas CB2Rs are predominantly expressed in peripheral immune cells.However,there is emerging strong evidence that CB2Rs are moderately expressed and function in specific brain areas.CB2Rs in the central nervous system (CNS) takes part in occurrence and progression of Alzheimer's disease,traumatic brain injury,intracranial hemorrhage and epilepsy.This review summarizes the CB2Rs and the effect in central nervous system disorders.