The Protective Effects of GPR55 Against Hippocampal Neuroinflammation and Neurogenic Damage in CSDS Mice

2021 ◽  
Author(s):  
Shiyu Shen ◽  
Rui Yu ◽  
Wei Li ◽  
Ling-Feng Liang ◽  
Qiuqin Han ◽  
...  
Keyword(s):  
Protein Level ◽  
Cannabinoid Receptor ◽  
Neuroprotective Effect ◽  
Hippocampal Neurogenesis ◽  
Mental Illnesses ◽  
Antidepressant Effect ◽  
Independent Experiment ◽  
Protective Effects ◽  
Depression And Anxiety ◽  
Animal Model Of Depression

Abstract BackgroundDepression is one of the most prevalent mental illnesses in the world today, the onset of depression is usually accompanied by neuroinflammation and neurogenic damage. Recently, G protein coupled receptor 55 (GPR55) has been associated with mood regulation as a third kind of cannabinoid receptor, and the activation of GPR55 was demonstrated recently to have a neuroprotective effect on hippocampal neurogenesis against inflammatory insult. However, its role in regulating depression and anxiety remains poorly understood.Methods10-day chronic social defeat stress (CSDS) was utilized as an animal model of depression to explore the potential antidepressant effect of GPR55 agonist and electroacupuncture (EA), a common therapy for depression in China. Several behavioral tests i.e. forced swimming test, open field test and elevated plus maze were performed to evaluate the depression- and anxiety-like behaviors in mice. Expression of GPR55, hippocampal neuroinflammation, and neurogenesis were detected using immunohistochemistry, western blot and RT-PCR. Then, the effect of a GPR55 agonist, O-1602 on depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis was examined. Furthermore, the potential antidepressant effect of 3-week EA treatment was also evaluated in another independent experiment. In the experiment, the behaviors and hippocampal neuroinflammation and neurogenesis were also subsequently examined.ResultsAfter CSDS, the protein level of GPR55 was decreased only in susceptible mice but the mRNA expression was not significantly different in all CSDS mice. Additionally, depression- and anxiety-like behaviors are accompanied by neuroinflammation and reduced neurogenesis in the hippocampus. And the activation of GPR55 during the process of CSDS prevented the development of depression- and anxiety- like behaviors, as well as hippocampal neuroinflammation and neurogenetic damage. Similarly, EA alleviated the depression- and anxiety-like behaviors, hippocampal neuroinflammation, and neurogenetic damage as well as decreased protein level of GPR55 in hippocampus induced by CSDS.ConclusionsOur research demonstrated that activation of hippocampal GPR55 could rescue depression and anxiety phenotypes, reduce hippocampal neuroinflammation, and enhance hippocampal neurogenesis. Moreover, GPR55 might be involved in the beneficial effect of EA on depression.

scholarly journals Rifaximin-Mediated Gut Microbiota Regulation Modulates the Polarization of Microglia During CUMS in Rat

2021 ◽  
Author(s):  
Haonan Li ◽  
Yujiao Xiang ◽  
Zemeng Zhu ◽  
Wei Wang ◽  
Zhijun Jiang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiome ◽  
Neuroprotective Effect ◽  
Short Chain Fatty Acids ◽  
Hippocampal Neurogenesis ◽  
Short Chain ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Fecal Microbiome ◽  
Chain Fatty Acids

Abstract Background: Chronic unpredictable mild stress (CUMS) can not only lead to depression-like behavior but also change the composition of the gut microbiome. Regulating the gut microbiome can have an antidepressant effect, but the mechanism by which it improves depressive symptoms is not clear. Short-chain fatty acids (SCFAs) are small molecular compounds produced by the fermentation of non-digestible carbohydrates. SFCAs are ubiquitous in intestinal endocrine and immune cells, making them important mediators of gut microbiome-regulated body functions. Activated M1 microglia can cause pro-inflammatory and neurotoxic effects, while M2 microglia serve anti-inflammatory and neuroprotective functions. The balance between the two phenotypes of microglia plays an important role in the occurrence and treatment of depression caused by chronic stress. We hypothesized that rifaximin exerts an antidepressant effect by changing the abundance of fecal SFCA metabolites and transforming the microglial phenotype. Methods: We administered 150 mg/kg rifaximin intragastrically to rats exposed to CUMS for 4 weeks and investigated the composition of the fecal microbiome, the content of short-chain fatty acids in the serum and brain, microglial phenotypic profiles and hippocampal neurogenesis. Results: Our results show that rifaximin ameliorated depressive-like behavior induced by CUMS, as reflected by sucrose preference, the open field test and the Morris water maze. Rifaximin increased the relative abundance of Ruminococcaceae, which were significantly positively correlated with high levels of butyrate in the brain. Rifaximin also increased the transformation of M1 microglia into the M2 type in the hippocampal dentate gyrus (DG) and ameliorated neurogenic abnormalities and functional deficits caused by CUMS.Conclusions: These results suggest that rifaximin can enhance the neuroprotective effect of microglia to some extent by regulating the gut microbiome and one of its metabolites, butyrate.

Neuroprotective and Antioxidant Effects of Riparin I in a Model of Depression Induced by Corticosterone in Female Mice

2021 ◽  
pp. 1-11
Author(s):  
Iris Cristina Maia Oliveira ◽  
Auriana Serra Vasconcelos Mallmann ◽  
Francisco Adelvane de Paula Rodrigues ◽  
Laura Maria Teodorio Vidal ◽  
Iardja Stéfane Lopes Sales ◽  
...  
Keyword(s):  
New Drugs ◽  
Antidepressant Effect ◽  
Therapeutic Drug ◽  
Female Mice ◽  
Potential Source ◽  
Treatment Of Depression ◽  
Animal Model Of Depression ◽  
Strong Candidate ◽  
Antioxidant Mechanisms ◽  
Antioxidant Effects

<b><i>Background:</i></b> Depression is a common, chronic, and often recurrent serious mood disorder. Conventional antidepressants present limitations that stimulate the search for new drugs. Antioxidant and neuroprotective substances are potential antidepressant agents. In this context, riparin I (RIP I) has presented promising results, emerging as a potential source of a new therapeutic drug. In this study, the antidepressant effect of RIP I was evaluated in an animal model of depression induced by corticosterone (CORT). The involvement of neuroprotective and antioxidant mechanisms in the generation of this effect was also assessed. <b><i>Methods:</i></b> Female mice were submitted to CORT for 21 days and treated with RIP I in the last 7 days. Behavioral and neurochemical analyses were performed. <b><i>Results:</i></b> The administration of RIP I reversed the depressive and psychotic-like behavior, as well as the cognitive impairment caused by CORT, in addition to regulating oxidative stress parameters and BDNF levels in depression-related brain areas. <b><i>Conclusion:</i></b> These findings suggest that RIP I can be a strong candidate for drugs in the treatment of depression.

scholarly journals Prevalence of Anxiety and Depression in Patients with Inflammatory Bowel Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Glynis Byrne ◽  
Greg Rosenfeld ◽  
Yvette Leung ◽  
Hong Qian ◽  
Julia Raudzus ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Multivariable Analysis ◽  
Significant Proportion ◽  
Mental Illnesses ◽  
Self Report ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Psychiatric Interview ◽  
Inflammatory Bowel

Background. Inflammatory bowel disease (IBD) patients are not routinely screened for depression and anxiety despite knowledge of an increased prevalence in people with chronic disease and negative effects on quality of life. Methods. Prevalence of anxiety and depression was assessed in IBD outpatients through retrospective chart review. The presence of anxiety and/or depression was determined using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 self-report questionnaires or by diagnosis through psychiatric interview. Patient demographics, disease characteristics, and medication information were also collected. Multivariable analysis was used to determine associations between patient factors and depression and anxiety. Results. 327 patient charts were reviewed. Rates of depression and anxiety were found to be 25.8% and 21.2%, with 30.3% of patients suffering from depression and/or anxiety. Disease activity was found to be significantly associated with depression and/or anxiety (p=0.01). Females were more likely to have anxiety (p=0.01). Conclusion. A significant proportion of IBD patients suffer from depression and/or anxiety. The rates of these mental illnesses would justify screening and referral for psychiatric treatment in clinics treating this population. Patients with active disease are particularly at risk for anxiety and depression.

scholarly journals Isorhynchophylline Protects PC12 Cells Against Beta-Amyloid-Induced Apoptosis via PI3K/Akt Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yan-Fang Xian ◽  
Zhi-Xiu Lin ◽  
Qing-Qiu Mao ◽  
Jian-Nan Chen ◽  
Zi-Ren Su ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Neuroprotective Effect ◽  
Protective Action ◽  
Protective Effects ◽  
Phosphorylated Akt ◽  
Induced Apoptosis

The neurotoxicity of amyloid-β(Aβ) has been implicated as a critical cause of Alzheimer’s disease. Isorhynchophylline (IRN), an oxindole alkaloid isolated fromUncaria rhynchophylla,exerts neuroprotective effect againstAβ25–35-induced neurotoxicityin vitro. However, the exact mechanism for its neuroprotective effect is not well understood. The present study aimed to investigate the molecular mechanisms underlying the protective action of IRN againstAβ25–35-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Pretreatment with IRN significantly increased the cell viability, inhibited the release of lactate dehydrogenase and the extent of DNA fragmentation inAβ25–35-treated cells. IRN treatment was able to enhance the protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3β(p-GSK-3β). Lithium chloride blockedAβ25–35-induced cellular apoptosis in a similar manner as IRN, suggesting that GSK-3βinhibition was involved in neuroprotective action of IRN. Pretreatment with LY294002 completely abolished the protective effects of IRN. Furthermore, IRN reversedAβ25–35-induced attenuation in the level of phosphorylated cyclic AMP response element binding protein (p-CREB) and the effect of IRN could be blocked by the PI3K inhibitor. These experimental findings unambiguously suggested that the protective effect of IRN againstAβ25–35-induced apoptosis in PC12 cells was associated with the enhancement of p-CREB expression via PI3K/Akt/GSK-3βsignaling pathway.

Effects of hyperbaric oxygen pretreatment on brain antioxidant capacity in rats with decompression sickness

2021 ◽  
pp. 287-295
Author(s):  
Ya Li ◽  
◽  
Xiaona Xu ◽  
Junxiang Bao Bao ◽  
Wenlan Wang ◽  
...  
Keyword(s):  
Hyperbaric Oxygen ◽  
Decompression Sickness ◽  
Neuroprotective Effect ◽  
Male Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Rat Models ◽  
Metal Elements ◽  
Flame Atomic Absorption ◽  
Brain Tissues

Objective: Decompression sickness (DCS) causes serious brain hypoxic-ischemic injury. This experiment was designed to observe whether hyperbaric oxygen (HBO2) pretreatment played a neuroprotective effect in decompression sickness rat models and to explore the mechanism of protective effects. Methods: Sprague-Dawley (SD) male rats were pretreated with HBO2 and then underwent decompression to establish the DCS rat model. Antioxidant capacities were evaluated by detecting peroxides (GPx), superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in brains. The levels of metal elements manganese (Mn), zinc (Zn), iron (Fe) and magnesium (Mg) in brain tissues were assessed by flame atomic absorption spectrometry. Necrosis and apoptosis of neurons were assessed by H-E staining and immunohistochemical staining. Results: HBO2 pretreatment reduced the degree of necrosis and apoptosis in brain tissues of decompression sickness rat models. In addition, HBO2 pretreatment increased GPx, SOD and CAT activities and reduced MDA accumulation. It also increased the content of Mn, Zn, Fe and Mg in brain tissue, which are all related to free radical metabolism. Conclusion: These results suggested that HBO2 pretreatment has protective effects on brain injury of rats with decompression sickness. The mechanism of the protective effects may be related to reducing oxidative damage by affecting metal elements in vivo.

scholarly journals Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice

2014 ◽  
Vol 22 (5) ◽  
pp. 453-459 ◽  
Author(s):  
Yang-Hee Jung ◽  
Sa-Ik Hong ◽  
Shi-Xun Ma ◽  
Ji-Young Hwang ◽  
Jun-Sup Kim ◽  
...  
Keyword(s):  
Animal Model ◽  
Strain Differences ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Depression And Anxiety ◽  
Animal Model Of Depression

scholarly journals Can Physical Activity Support the Endocannabinoid System in the Preventive and Therapeutic Approach to Neurological Disorders?

2020 ◽  
Vol 21 (12) ◽  
pp. 4221
Author(s):  
Tomasz Charytoniuk ◽  
Hubert Zywno ◽  
Karolina Konstantynowicz-Nowicka ◽  
Klaudia Berk ◽  
Wiktor Bzdega ◽  
...  
Keyword(s):  
Physical Activity ◽  
Neurodegenerative Disorders ◽  
Therapeutic Approach ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoids ◽  
Endocannabinoid System ◽  
Antidepressant Effect ◽  
Brain Physiology ◽  
Current State ◽  
Neurological Effects

The worldwide prevalence of neurological and neurodegenerative disorders, such as depression or Alzheimer’s disease, has spread extensively throughout the last decades, becoming an enormous health issue. Numerous data indicate a distinct correlation between the altered endocannabinoid signaling and different aspects of brain physiology, such as memory or neurogenesis. Moreover, the endocannabinoid system is widely regarded as a crucial factor in the development of neuropathologies. Thus, targeting those disorders via synthetic cannabinoids, as well as phytocannabinoids, becomes a widespread research issue. Over the last decade, the endocannabinoid system has been extensively studied for its correlation with physical activity. Recent data showed that physical activity correlates with elevated endocannabinoid serum concentrations and increased cannabinoid receptor type 1 (CB1R) expression in the brain, which results in positive neurological effects including antidepressant effect, ameliorated memory, neuroplasticity development, and reduced neuroinflammation. However, none of the prior reviews presented a comprehensive correlation between physical activity, the endocannabinoid system, and neuropathologies. Thus, our review provides a current state of knowledge of the endocannabinoid system, its action in physical activity, as well as neuropathologies and a possible correlation between all those fields. We believe that this might contribute to finding a new preventive and therapeutic approach to both neurological and neurodegenerative disorders.

scholarly journals Ketamine—New Possibilities in the Treatment of Depression: A Narrative Review

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1186
Author(s):  
Mateusz Kowalczyk ◽  
Edward Kowalczyk ◽  
Paweł Kwiatkowski ◽  
Łukasz Łopusiewicz ◽  
Monika Sienkiewicz ◽  
...  
Keyword(s):  
Antidepressant Effect ◽  
Depression Symptoms ◽  
Drug Resistant ◽  
Depression And Anxiety ◽  
Psychoactive Substances ◽  
Worldwide Population ◽  
Treatment Of Depression ◽  
Resistant Depression ◽  
Depressive Episodes ◽  
Rapid Treatment

The SARS-CoV-2 coronavirus epidemic has led to an increase in the number of people with depression. Symptoms related to the mental sphere (mainly depression and anxiety) may be experienced by one third of the worldwide population. This entails the need for the effective and rapid treatment of depressive episodes. An effective drug seems to be s-ketamine, which was accepted in March 2019 by the Food and Drug Administration (FDA) for the treatment of drug-resistant depression. This drug provides a quick antidepressant effect with maximum effectiveness achieved after 24 h. It also appears to reduce the occurrence of suicidal thoughts. However, research into undesirable effects, especially in groups of people susceptible to psychotic episodes or those who use alcohol or psychoactive substances, is necessary.

scholarly journals Effect of curcumin in the acute phase of ischemia in chronic cerebral hypoperfusion in rats

2018 ◽  
Vol 17 (1) ◽  
pp. 69-73
Author(s):  
N. S. Shcherbak ◽  
M. A. Popovetskiy ◽  
G. Yu. Yukina ◽  
M. M. Galagudza
Keyword(s):  
Brain Injury ◽  
Acute Phase ◽  
Wistar Rats ◽  
Neuroprotective Effect ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Ischemic Brain Injury ◽  
Protective Effects ◽  
Single Application ◽  
Ischemic Brain

Curcumin presents antioxidant and anti-inflammatory properties and can be considered as a neuroprotector. Data on doses and duration of application of curcumin to achieve protective effects in various types of ischemic brain injury is controversial. The purpose was to study the neuroprotective properties of curcumin in the acute phase of ischemia in chronic cerebral hypoperfusion in rats. It is shown that a single application of curcumin (300 mg/kg, i.p.) is not has neuroprotective effect in the acute phase of ischemia in chronic hypoperfusion in Wistar rats. The results allow to conclude that the neuroprotective effect of a single application of curcumin.

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