scholarly journals Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals

2021 ◽  
Vol 22 (22) ◽  
pp. 12551
Author(s):  
Silvia Diviccaro ◽  
Valentina Caputi ◽  
Lucia Cioffi ◽  
Silvia Giatti ◽  
Joshua M. Lyte ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Steroid Hormones ◽  
Endocrine System ◽  
Neuroactive Steroids ◽  
Brain Functioning ◽  
Germ Free ◽  
Liquid Chromatography Tandem Mass ◽  
Nervous Function ◽  
The Impact ◽  
The Brain

Steroid hormones are essential biomolecules for human physiology as they modulate the endocrine system, nervous function and behaviour. Recent studies have shown that the gut microbiota is directly involved in the production and metabolism of steroid hormones in the periphery. However, the influence of the gut microbiota on levels of steroids acting and present in the brain (i.e., neuroactive steroids) is not fully understood. Therefore, using liquid chromatography–tandem mass spectrometry, we assessed the levels of several neuroactive steroids in various brain areas and the plasma of germ-free (GF) male mice and conventionally colonized controls. The data obtained indicate an increase in allopregnanolone levels associated with a decrease in those of 5α-androstane-3α, 17β-diol (3α-diol) in the plasma of GF mice. Moreover, an increase of dihydroprogesterone and isoallopregnanolone in the hippocampus, cerebellum, and cerebral cortex was also reported. Changes in dihydrotestosterone and 3α-diol levels were also observed in the hippocampus of GF mice. In addition, an increase in dehydroepiandrosterone was associated with a decrease in testosterone levels in the hypothalamus of GF mice. Our findings suggest that the absence of microbes affects the neuroactive steroids in the periphery and the brain, supporting the evidence of a microbiota-mediated modulation of neuroendocrine pathways involved in preserving host brain functioning.

scholarly journals DDRE-14. HEMP DERIVED EXTRACELLULAR VESICLES (EVS): A POTENTIAL ANTI-GLIOMA THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii64-ii64
Author(s):  
Hassan Azari ◽  
Nasser Nassiri Koopaei ◽  
Mohammad-Zaman Nouri ◽  
Jesse D Hall ◽  
Nancy D Denslow ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Extracellular Vesicles ◽  
Chromatography Tandem Mass Spectrometry ◽  
Anti Cancer ◽  
Liquid Chromatography Tandem Mass ◽  
Median Diameter ◽  
The Impact ◽  
The Brain ◽  
Plant Sources

Abstract INTRODUCTION Extracellular vesicles (EVs) have been harvested from many plant sources, some of which have anti-cancer effects and some could be used as therapeutic nanodelivery vectors. Hemp plant is a natural source of cannabinoids, of which delta 9-tetrahydroxicannabinol (THC) and cannabidiol (CBD) have proven anti-cancer proprieties. HYPOTHESIS We hypothesized that hemp EVs are enriched in cannabinoids and their application will reduce glioblastoma (GBM) tumor progression. APPROACH EVs were isolated from the hemp plant using ultracentrifugation. Nanotracking analysis, electron microscopy and liquid chromatography tandem mass spectrometry (LC-MS/MS) were utilized to characterize EVs. GBM cell lines were cultured in the neuropshere assay to evaluate hemp EVs anti-glioma effects. Fluorescent-labelled EVs were used to evaluate their brain tissue distribution in orthotopic patient-derived GBM xenografts. RESULTS Hemp EVs have a median diameter of 112.6nm with a typical lipid-bilayer structure. LC-MS/MS have shown that while cannabidiolic, cannabigerolic, and tetrahydroxicannabinolic acids represent 69.1 ± 2.1%, 19.1 ± 1.6%, 6.5 ± 0.54% of the total cannabinoids in hemp EVs, CBD and THC only make 4.75 ± 0.26%, and 0.5 ± 0.3%. Hemp EVs are potent anti-glioma agents with a 7-day LD-50 of 1.04µM and 2.4µM [based on EVs total cannabinoid content] for KR-158 and L0 GBM lines, respectively. Compared to the vehicle, overnight incubation of L0 cells with 1µM hemp EVs significantly reduced GBM cell migration (630.3 ± 61.43 vs 143.7 ± 8.7). Intranasal administration of hemp EVs led to a widespread distribution in tumor bearing brain including GBM tumor core. CONCLUSION Based on these results, hemp EVs with enriched cannabinoid content exert antiglioma effect in-vitro and when delivered intranasally, are widely distributed throughout the brain and within the tumor of PDX animals. Further experiments are ongoing to address the impact of nasally-delivered hemp EVs on tumor progression and compare to the application of purified acidic cannabinoids.

scholarly journals Current Paradigms to Explore the Gut Microbiota Linkage to Neurological Disorders

EMJ Neurology ◽  
2020 ◽  
pp. 68-79
Author(s):  
Varruchi Sharma ◽  
Atul Sankhyan ◽  
Anshika Varshney ◽  
Renuka Choudhary ◽  
Anil K. Sharma
Keyword(s):  
Gut Microbiota ◽  
Neurological Disorders ◽  
Brain Function ◽  
Intervention Strategy ◽  
Neurological Complications ◽  
Communication Link ◽  
Brain Functions ◽  
Current Review ◽  
The Impact ◽  
The Brain

It has been suggested that an intricate communication link exists between the gut microbiota and the brain and its ability to modulate behaviour of an individual governing homeostasis. Metabolic activity of the microbiota is considered to be relatively constant in healthy individuals, despite differences in the composition of microbiota. The metabolites produced by gut microbiota and their homeostatic balance is often perturbed as a result of neurological complications. Therefore, it is of paramount importance to explore the link between gut microbiota and brain function and behaviour through neural, endocrine, and immune pathways. This current review focusses on the impact of altered gut microbiota on brain functions and how microbiome modulation by use of probiotics, prebiotics, and synbiotics might prove beneficial in the prevention and/or treatment of neurological disorders. It is important to carefully understand the complex mechanisms underlying the gut–brain axis so as to use the gut microbiota as a therapeutic intervention strategy for neurological disorders.

Gut Microbiota and Alzheimer’s Disease: Experimental Evidence and Clinical Reality

2021 ◽  
Vol 18 ◽  
Author(s):  
Sarama Saha ◽  
Sukhpal Singh ◽  
Suvarna Prasad ◽  
Amit Mittal ◽  
Anil Kumar Sharma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Experimental Evidence ◽  
Molecular Mechanisms ◽  
Bacterial Flora ◽  
Experimental Studies ◽  
The Elderly ◽  
The Impact ◽  
The Brain

: Alzheimer’s disease (AD) is characterized by progressive death of neuronal cells in the regions of the brain concerned with memory and cognition, and is the major cause of dementia in the elderly population. Various molecular mechanisms, metabolic risk factors and environmental triggers contributing to the genesis and progression of AD are under intense investigations. The present review has dealt with the impact of a highly discussed topic of gut microbiota affecting the neurodegeneration in the AD brain. A detailed description of the composition of gut bacterial flora and its interaction with the host has been presented, followed by an analysis of key concepts of bi- directional communication between gut microbiota and the brain. The substantial experimental evidence of gut microbiota affecting the neurodegenerative process in experimental AD models has been described next in this review, and finally, the limitations of such experimental studies vis-a- vis the actual disease and the paucity of clinical data on this topic have also been mentioned.

scholarly journals Endobolome, a New Concept for Determining the Influence of Microbiota Disrupting Chemicals (MDC) in Relation to Specific Endocrine Pathogenesis

2020 ◽  
Vol 11 ◽  
Author(s):  
Margarita Aguilera ◽  
Yolanda Gálvez-Ontiveros ◽  
Ana Rivas
Keyword(s):  
Gut Microbiota ◽  
Steroid Hormones ◽  
Endocrine Disrupting Chemicals ◽  
Epidemiological Studies ◽  
Host Susceptibility ◽  
Research Strategies ◽  
Microbial Composition ◽  
Endocrine Disrupting ◽  
The Impact

Endogenous steroid hormones and Endocrine Disrupting Chemicals (EDC) interact with gut microbiota through different pathways. We suggest the use of the term “endobolome” when referring to the group of gut microbiota genes and pathways involved in the metabolism of steroid hormones and EDC. States of dysbiosis and reduced diversity of the gut microbiota may impact and modify the endobolome resulting at long-term in the development of certain pathophysiological conditions. The endobolome might play a central role in the gut microbiota as seen by the amount of potentially endobolome-mediated diseases and thereby it can be considered an useful diagnostic tool and therapeutic target for future functional research strategies that envisage the use of next generation of probiotics. In addition, we propose that EDC and other xenobiotics that alter the gut microbial composition and its metabolic capacities should be categorized into a subgroup termed “microbiota disrupting chemicals” (MDC). This will help to distinguish the role of contaminants from other microbiota natural modifiers such as those contained or released from diet, environment, physical activity and stress. These MDC might have the ability to promote specific changes in the microbiota that can ultimately result in common intestinal and chronic or long-term systemic diseases in the host. The risk of developing certain disorders associated with gut microbiota changes should be established by determining both the effects of the MDC on gut microbiota and the impact of microbiota changes on chemicals metabolism and host susceptibility. In any case, further animal controlled experiments, clinical trials and large epidemiological studies are required in order to establish the concatenated impact of the MDC-microbiota-host health axis.

scholarly journals Protective Actions of 17β-Estradiol and Progesterone on Oxidative Neuronal Injury Induced by Organometallic Compounds

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Yasuhiro Ishihara ◽  
Takuya Takemoto ◽  
Atsuhiko Ishida ◽  
Takeshi Yamazaki
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Steroid Hormones ◽  
Endocrine System ◽  
Organometallic Compounds ◽  
Neuronal Injury ◽  
Neuroactive Steroids ◽  
The Central Nervous System ◽  
Neuroprotective Actions ◽  
Pass Through

Steroid hormones synthesized in and secreted from peripheral endocrine glands pass through the blood-brain barrier and play a role in the central nervous system. In addition, the brain possesses an inherent endocrine system and synthesizes steroid hormones known as neurosteroids. Increasing evidence shows that neuroactive steroids protect the central nervous system from various harmful stimuli. Reports show that the neuroprotective actions of steroid hormones attenuate oxidative stress. In this review, we summarize the antioxidative effects of neuroactive steroids, especially 17β-estradiol and progesterone, on neuronal injury in the central nervous system under various pathological conditions, and then describe our recent findings concerning the neuroprotective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds, tributyltin, and methylmercury.

scholarly journals Gut-derived Metabolites Influence Neurodevelopmental Gene Expression and Wnt Signalling Events in a Germ-free Zebrafish Model

2022 ◽  
Author(s):  
Terry Van Raay ◽  
Victoria Rea ◽  
Ian Bell
Keyword(s):  
Gene Expression ◽  
Neural Development ◽  
Morphological Changes ◽  
Wnt Signalling ◽  
Gene Ontology Analysis ◽  
Rna Seq ◽  
Zebrafish Model ◽  
Germ Free ◽  
The Impact ◽  
The Brain

Abstract Background : Small molecule metabolites produced by the microbiome are known to be neuroactive and are capable of directly impacting the brain and central nervous system, yet there is little data on the contribution of these metabolites to the earliest stages of neural development and neural gene expression. Here, we explore the impact of deriving zebrafish embryos in the absence of microbes on early neural development as well as investigate whether any potential changes can be rescued with treatment of metabolites derived from the zebrafish gut microbiota. Results : Overall, we did not observe any gross morphological changes between treatments but did observe a significant decrease in neural gene expression in embryos raised germ-free, which was rescued with the addition of zebrafish metabolites. Specifically, we identified 354 genes significantly down regulated in germ-free embryos compared to conventionally raised embryos via RNA-Seq analysis. Of these, 42 were rescued with a single treatment of zebrafish gut-derived metabolites to germ-free embryos. Gene ontology analysis revealed that these genes are involved in prominent neurodevelopmental pathways including transcriptional regulation and Wnt signalling. Consistent with the ontology analysis, we found alterations in the development of Wnt dependent events which was rescued in the germ-free embryos treated with metabolites. Conclusions : These findings demonstrate that gut-derived metabolites are in part responsible for regulating critical signalling pathways in the brain, especially during neural development.

scholarly journals Modulation of the gut microbiota-adipose tissue-muscle interactions by prebiotics

2021 ◽  
Author(s):  
Julie Rodriguez ◽  
Nathalie M Delzenne
Keyword(s):  
Adipose Tissue ◽  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Metabolic Functions ◽  
Promising Strategy ◽  
Gut Hormone ◽  
Intestinal Functions ◽  
Host Metabolism ◽  
The Impact ◽  
The Brain

The gut microbiota is now widely recognized as an important factor contributing to the regulation of host metabolic functions. Numerous studies describe an imbalance in the gut microbial ecosystem in response to an energy-dense diet that drives the development of metabolic disorders. In this context, the manipulation of the gut microbiota by food components acting as prebiotics appears as a promising strategy. Several studies have already investigated the beneficial potency of prebiotics, mostly inulin type fructans, on host metabolism and key intestinal functions including gut hormone release. For the last 20 years, several non-digestible compounds present in food have been shown to modulate the gut microbiota and influence host metabolism in essential organs involved in the control of energy homeostasis. To date, numerous reviews summarize the impact of prebiotics on the liver or the brain. Here we propose to describe the mechanisms by which prebiotics, through modulation of the gut microbiota and endocrine functions, modulates the metabolic cross-talk communication between the gut, the adipose tissue and skeletal muscles.

scholarly journals Gut-derived metabolites influence neurodevelopmental gene expression and Wnt signalling events in a germ-free zebrafish model

2021 ◽  
Author(s):  
Victoria Rea ◽  
Ian Bell ◽  
Terence J Van Raay
Keyword(s):  
Gene Expression ◽  
Neural Development ◽  
Morphological Changes ◽  
Wnt Signalling ◽  
Gene Ontology Analysis ◽  
Rna Seq ◽  
Zebrafish Model ◽  
Germ Free ◽  
The Impact ◽  
The Brain

Small molecule metabolites produced by the microbiome are known to be neuroactive and are capable of directly impacting the brain and central nervous system, yet there is little data on the contribution of these metabolites to the earliest stages of neural development and neural gene expression. Here, we explore the impact of rearing zebrafish embryos in the absence of microbes on early neural development as well as investigate whether any potential changes can be rescued with treatment of metabolites derived from the zebrafish gut microbiota. Overall, we did not observe any gross morphological changes between treatments but did observe a significant decrease in neural gene expression in embryos raised germ-free, which was rescued with the addition of zebrafish metabolites. Specifically, we identified 361 genes significantly down regulated in GF embryos compared to conventionally raised embryos via RNA-Seq analysis. Of these, 42 were rescued with the treatment of zebrafish gut-derived metabolites to GF embryos. Gene ontology analysis revealed that these genes are involved in prominent neurodevelopmental pathways including transcriptional regulation and Wnt signalling. Consistent with the ontology analysis, we found alterations in the development of Wnt dependent events which is rescued in the GF embryos treated with metabolites.

Using Creative Arts in Trauma Therapy: The Neuroscience of Healing

2019 ◽  
Vol 41 (1) ◽  
pp. 80-94 ◽  
Author(s):  
Kristi Perryman ◽  
Paul Blisard ◽  
Rochelle Moss
Keyword(s):  
Traumatic Event ◽  
Emotional Experience ◽  
Body Movement ◽  
Creative Arts ◽  
Brain Functioning ◽  
Corrective Emotional Experience ◽  
Assessment And Treatment ◽  
Corrective Experience ◽  
The Impact ◽  
The Brain

Knowledge about the brain and the impact of trauma has increased significantly in recent years. Counselors must understand brain functioning and the effects of trauma in order to choose the most effective methods for working with clients. Creative arts therapies offer a nonthreatening way for clients to access and express their trauma, creating a corrective experience in the brain. Activities that incorporate body movement can be particularly helpful by providing a corrective emotional experience for those clients with an immobilized response to a traumatic event. This article offers a model for the assessment and treatment of trauma through the use of creative arts.

scholarly journals Using a Model of Germ-Free Animals to Study the Impact of Gut Microbiome in Research: A Step by Step Sterility Setting and Management

2020 ◽  
Vol 3 (1) ◽  
pp. 18
Author(s):  
Odile Gabay ◽  
Jonathan Vicenty ◽  
Dylan Smith ◽  
Linda Tiffany ◽  
Jill Ascher ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immunological Response ◽  
Disease Status ◽  
Germ Free ◽  
Therapeutic Modalities ◽  
Current Therapies ◽  
Patient Responses ◽  
Unique Composition ◽  
And Control ◽  
The Impact

The particularly unique composition of the gut microbiota has the potential to influence the health or disease status of animal and human hosts. Altering the homeostasis of the host-bacteria could lead to changes in gut flora that result in disease or activation of a specific immunological response, which could explain the variations observed in patient responses to current therapies. A standardized model is crucial for studying the influence of the gut microbiota on therapeutic modalities. A step by step mouse model and sterility management system that compares a control strain of C57BL/6 mice to the established C57BL/6 germ-free (GF) strain has been developed. The GF BL/6 mouse phenotype is well established, and the anatomical differences between the GF and control mice were evident in this model. This method could be applied to research studies investigating the microbiome impact, the response to various therapies, or disease transfer via fecal transplants. A standardized sterility maintenance method is crucial in this context.

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