(R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: A role of gut–microbiota–brain axis

Wang, Xingming; Chang, Lijia; Wan, Xiayun; Tan, Yunfei; Qu, Youge; Shan, Jiajing; Yang, Yong; Ma, Li; Hashimoto, Kenji

doi:10.1016/j.nbd.2022.105635

Cited by 47 publications

(27 citation statements)

References 76 publications

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“…In most cases, histological and ultrastructural readouts are performed to evaluate the effectiveness of novel treatment strategies. Luxol-fast blue stains and immunohistochemistry using antibodies directed against major myelin proteins such as anti-proteolipid protein (PLP) or anti-myelin basic protein (MBP), for example, are frequently applied to estimate the myelination levels of the region of interest [ 36 , 37 , 38 ]. Ultrastructural studies using electron microscopy can verify the histological results and analyze the axonal myelin diameter ratio, also called “G-ratio”, which is believed to be a sensitive marker for remyelinated axons [ 39 ].…”

Section: Preclinical Ms Modelsmentioning

confidence: 99%

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

Lubrich

Giesler

Kipp

2022

IJMS

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Multiple Sclerosis (MS) is a neuroinflammatory disorder, which is histopathologically characterized by multifocal inflammatory demyelinating lesions affecting both the central nervous system’s white and grey matter. Especially during the progressive phases of the disease, immunomodulatory treatment strategies lose their effectiveness. To develop novel progressive MS treatment options, pre-clinical animal models are indispensable. Among the various different models, the cuprizone de- and remyelination model is frequently used. While most studies determine tissue damage and repair at the histological and ultrastructural level, functional readouts are less commonly applied. Among the various overt functional deficits, gait and coordination abnormalities are commonly observed in MS patients. Motor behavior is mediated by a complex neural network that originates in the cortex and terminates in the skeletal muscles. Several methods exist to determine gait abnormalities in small rodents, including the rotarod testing paradigm. In this review article, we provide an overview of the validity and characteristics of the rotarod test in cuprizone-intoxicated mice.

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Section: Preclinical Ms Modelsmentioning

confidence: 99%

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

Lubrich

Giesler

Kipp

2022

IJMS

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“…This may explain why (R)-ketamine has a greater and longer-lasting potency than (S)-ketamine. Other studies have shown that (R)-ketamine-mediated changes in GM are associated with the activation of microglia and bone mineral density, which is also inextricably linked to depression Wang et al, 2022). Other first-line nervous systems drugs, such as sertraline, imipramine, and chlorpromazine, have also shown regulatory potential in these pathways in the GM.…”

Section: Classic Antidepressantsmentioning

confidence: 99%

Reviewing the role of gut microbiota in the pathogenesis of depression and exploring new therapeutic options

Han

Wang²,

Han³

et al. 2022

Front. Neurosci.

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The relationship between gut microbiota (GM) and mental health is one of the focuses of psychobiology research. In recent years, the microbial-gut-brain axis (MGBA) concept has gradually formed about this bidirectional communication between gut and brain. But how the GM is involved in regulating brain function and how they affect emotional disorders these mechanisms are tenuous and limited to animal research, and often controversial. Therefore, in this review, we attempt to summarize and categorize the latest advances in current research on the mechanisms of GM and depression to provide valid information for future diagnoses and therapy of mental disorders. Finally, we introduced some antidepressant regimens that can help restore gut dysbiosis, including classic antidepressants, Chinese materia medica (CMM), diet, and exogenous strains. These studies provide further insight into GM’s role and potential pathways in emotion-related diseases, which holds essential possible clinical outcomes for people with depression or related psychiatric disorders. Future research should focus on clarifying the causal role of GM in disease and developing microbial targets, applying these findings to the prevention and treatment of depression.

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Section: Strategies For Improving the Pathophysiology Of Msmentioning

confidence: 99%

“…Another promising evidence arrives from the data, obtained by Chinese researchers ( 146 ), about the treatment with antidepressant (R)-ketamine in cuprizone (CPZ)-treated mice and remyelination after CPZ withdrawal. Precisely, they have recently demonstrated that the repeated treatment with (R)-ketamine (10 mg/kg/day, twice weekly, for 6 weeks) significantly ameliorated demyelination and activated microglia in the brain compared with saline-treated mice ( 146 ). In addition, it has been shown that the pretreatment with a TrkB antagonist, the ANA-12, significantly inhibited the beneficial effects of (R)-ketamine on the demyelination and activated microglia in the brain of CPZ-treated mice.…”

Section: Strategies For Improving the Pathophysiology Of Msmentioning

confidence: 99%

“…Accordingly, significant correlations between the demyelination (or microglial activation) in the brain and the relative quantity of several microbiomes were detected, suggesting a close relationship between gut microbiota and brain. These relevant results have led the Dr. X Wang group to suggest that (R)-ketamine could likely be a new therapeutic drug for MS ( 146 ).…”

Section: Strategies For Improving the Pathophysiology Of Msmentioning

confidence: 99%

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A Brief Overview on BDNF-Trk Pathway in the Nervous System: A Potential Biomarker or Possible Target in Treatment of Multiple Sclerosis?

et al. 2022

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The growing incidence of neurodegenerative disorders in our populations is leading the research to identify potential biomarkers and targets for facilitating their early management and treatments. Biomarkers represent the crucial indicators of both physiological and pathological processes. Specific changes in molecular and cellular mechanisms of physiological processes result in biochemical alterations at systemic level, which can give us comprehensive information regarding the nature of any disease. In addition, any disease biomarker should be specific and reliable, able to consent of distinguishing the physiological condition of a tissue, organ, or system from disease, and be diverse among the various diseases, or subgroups or phenotypes of them. Accordingly, biomarkers can predict chances for diseases, facilitate their early diagnosis, and set guidelines for the development of new therapies for treating diseases and disease-making process. Here, we focus our attention on brain neurotrophic factor (BDNF)–tropomyosin receptor kinase (Trk) pathway, describing its multiple roles in the maintenance of central nervous system (CNS) health, as well as its implication in the pathogenesis of multiple sclerosis (MS). In addition, we also evidence the features of such pathway, which make of it a potential MS biomarker and therapeutic target.

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(R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: A role of gut–microbiota–brain axis

Cited by 47 publications

References 76 publications

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

Reviewing the role of gut microbiota in the pathogenesis of depression and exploring new therapeutic options

A Brief Overview on BDNF-Trk Pathway in the Nervous System: A Potential Biomarker or Possible Target in Treatment of Multiple Sclerosis?

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