scholarly journals The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eldin Jašarević ◽  
Elizabeth M. Hill ◽  
Patrick J. Kane ◽  
Lindsay Rutt ◽  
Trevonn Gyles ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Microbial Communities ◽  
Relevant Model ◽  
Fetal Mice ◽  
Specific Manner ◽  
Health And Development ◽  
Offspring Health ◽  
The Brain ◽  
Offspring Mortality

AbstractNewborns are colonized by maternal microbiota that is essential for offspring health and development. The composition of these pioneer communities exhibits individual differences, but the importance of this early-life heterogeneity to health outcomes is not understood. Here we validate a human microbiota-associated model in which fetal mice are cesarean delivered and gavaged with defined human vaginal microbial communities. This model replicates the inoculation that occurs during vaginal birth and reveals lasting effects on offspring metabolism, immunity, and the brain in a community-specific manner. This microbial effect is amplified by prior gestation in a maternal obesogenic or vaginal dysbiotic environment where placental and fetal ileum development are altered, and an augmented immune response increases rates of offspring mortality. Collectively, we describe a translationally relevant model to examine the defined role of specific human microbial communities on offspring health outcomes, and demonstrate that the prenatal environment dramatically shapes the postnatal response to inoculation.

scholarly journals Estrogen Receptors Alpha and Beta Mediate Synaptic Transmission in the PFC and Hippocampus of Mice

2021 ◽  
Vol 22 (3) ◽  
pp. 1485
Author(s):  
Mingyue Zhang ◽  
Hannah Weiland ◽  
Michael Schöfbänker ◽  
Weiqi Zhang
Keyword(s):  
Estrogen Receptor ◽  
Synaptic Transmission ◽  
Estrogen Receptors ◽  
Hippocampal Slices ◽  
Physiological Role ◽  
Glutamatergic Transmission ◽  
Postsynaptic Currents ◽  
Specific Manner ◽  
The Brain

Distinct from ovarian estradiol, the steroid hormone 17ß-estradiol (E2) is produced in the brain and is involved in numerous functions, particularly acting as a neurosteroid. However, the physiological role of E2 and the mechanism of its effects are not well known. In hippocampal slices, 17ß-estradiol has been found to cause a modest increase in fast glutamatergic transmission; because some of these effects are rapid and acute, they might be mediated by membrane-associated receptors via nongenomic action. Moreover, activation of membrane estrogen receptors can rapidly modulate neuron function in a sex-specific manner. To further investigate the neurological role of E2, we examined the effect of E2, as an estrogen receptor (ER) agonist, on synaptic transmission in slices of the prefrontal cortex (PFC) and hippocampus in both male and female mice. Whole-cell recordings of spontaneous excitatory postsynaptic currents (sEPSC) in the PFC showed that E2 acts as a neuromodulator in glutamatergic transmission in the PFC in both sexes, but often in a cell-specific manner. The sEPSC amplitude and/or frequency responded to E2 in three ways, namely by significantly increasing, decreasing or having no response. Additional experiments using an agonist selective for ERß, diarylpropionitrile (DPN) showed that in males the sEPSC and spontaneous inhibitory postsynaptic currents sIPSC responses were similar to their E2 responses, but in females the estrogen receptor ß (ERß) agonist DPN did not influence excitatory transmission in the PFC. In contrast, in the hippocampus of both sexes E2 potentiated the gluatmatergic synaptic transmission in a subset of hippocampal cells. These data indicate that activation of E2 targeting probably a estrogen subtypes or different downstream signaling affect synaptic transmission in the brain PFC and hippocampus between males versus females mice.

scholarly journals 838 The role of microbiota in metastatic brain tumors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A879-A879
Author(s):  
Sarah Johnson ◽  
Golnaz Morad ◽  
Nadim Ajami ◽  
Jennifer Wargo ◽  
Matthew Wong ◽  
...  
Keyword(s):  
T Cell ◽  
Brain Metastasis ◽  
Gut Microbiota ◽  
Tumor Growth ◽  
Microbial Communities ◽  
Clinical Studies ◽  
Cell Activity ◽  
The Brain

BackgroundDespite the substantial advances in the treatment of systemic cancer, brain metastases are still responsible for significant morbidity and mortality, necessitating a better understanding of the mechanisms underlying this disease. Microbiota has emerged as a significant hallmark of cancer. Our group and others have demonstrated a prominent role for gut and intratumoral microbiota in tumorigenesis, tumor immunity, and response to treatment. However, the role of microbiota in brain metastasis is poorly understood. We hypothesize that distinct microbial communities can alter the immune microenvironment in the brain and modulate the different steps of brain metastasis formation.MethodsTo explore the role of microbiota in brain metastasis, we evaluated the gut and oral microbial signatures in brain metastasis patients through shotgun metagenomics sequencing. Furthermore, we conducted mechanistic in vivo studies in which the gut microbiota was depleted in conventionally raised mice using a broad-spectrum non-absorbable antibiotic regimen. Subsequently, melanoma tumor cells were injected intracranially to evaluate the effect of gut microbiota depletion and associated immune changes on tumor growth. Tumor growth was measured through in vivo bioluminescent imaging and histology. Peripheral and tumor immune profiling was conducted through flow cytometry and immunohistochemistry.ResultsOur clinical studies demonstrated the enrichment of distinct bacterial and viral taxa within the gut and oral microbiota in brain metastasis patients. Depletion of the gut microbiota in mice decreased tumor growth in the brain. Evaluation of the peripheral and tumor immune profiles suggested the underlying mechanisms to involve alterations in the circulating cytokine profiles and an increase in anti-tumor T cell activity.ConclusionsOur clinical studies suggest the association of distinct microbial communities with brain metastasis. Our pre-clinical findings demonstrate that the absence of gut microbiota can modulate the regulation of T cell activity to induce an anti-tumor response in the brain. Further studies, currently in progress, will determine the mechanistic role of dysbiotic microbiota and distinct microbial communities in this process.AcknowledgementsThis work was supported by the National Institute of Health (1F32CA260769-01).

The Role of Mitochondria in the Genesis of Neuroaxonal Dystrophy in the Brains of Aging Mice

1975 ◽  
Vol 33 ◽  
pp. 372-373
Author(s):  
J.E. Johnson
Keyword(s):  
Electron Microscopy ◽  
Present Report ◽  
Light And Electron Microscopy ◽  
Dorsal Column ◽  
Neuroaxonal Dystrophy ◽  
Nucleus Gracilis ◽  
Dystrophic Axons ◽  
The Brain ◽  
Nucleus Cuneatus

Although neuroaxonal dystrophy (NAD) has been examined by light and electron microscopy for years, the nature of the components in the dystrophic axons is not well understood. The present report examines nucleus gracilis and cuneatus (the dorsal column nuclei) in the brain stem of aging mice.Mice (C57BL/6J) were sacrificed by aldehyde perfusion at ages ranging from 3 months to 23 months. Several brain areas and parts of other organs were processed for electron microscopy.At 3 months of age, very little evidence of NAD can be discerned by light microscopy. At the EM level, a few axons are found to contain dystrophic material. By 23 months of age, the entire nucleus gracilis is filled with dystrophic axons. Much less NAD is seen in nucleus cuneatus by comparison. The most recurrent pattern of NAD is an enlarged profile, in the center of which is a mass of reticulated material (reticulated portion; or RP).

Chronic Pain: Fundamental Scientific Considerations, Specifically for Legal Claims

2013 ◽  
Vol 18 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Robert J. Barth
Keyword(s):  
Health Outcomes ◽  
Pain Perception ◽  
Driving Forces ◽  
Psychological Treatment ◽  
Dominant Role ◽  
Meta Analysis ◽  
General Medicine ◽  
Pain Syndrome ◽  
Problematic Relationship

Abstract Scientific findings have indicated that psychological and social factors are the driving forces behind most chronic benign pain presentations, especially in a claim context, and are relevant to at least three of the AMA Guides publications: AMA Guides to Evaluation of Disease and Injury Causation, AMA Guides to Work Ability and Return to Work, and AMA Guides to the Evaluation of Permanent Impairment. The author reviews and summarizes studies that have identified the dominant role of financial, psychological, and other non–general medicine factors in patients who report low back pain. For example, one meta-analysis found that compensation results in an increase in pain perception and a reduction in the ability to benefit from medical and psychological treatment. Other studies have found a correlation between the level of compensation and health outcomes (greater compensation is associated with worse outcomes), and legal systems that discourage compensation for pain produce better health outcomes. One study found that, among persons with carpal tunnel syndrome, claimants had worse outcomes than nonclaimants despite receiving more treatment; another examined the problematic relationship between complex regional pain syndrome (CRPS) and compensation and found that cases of CRPS are dominated by legal claims, a disparity that highlights the dominant role of compensation. Workers’ compensation claimants are almost never evaluated for personality disorders or mental illness. The article concludes with recommendations that evaluators can consider in individual cases.

Fibrinolytic Activity of Cerebro-Spinal Fluid and the Development of Artificial Cerebral Haematomas in Dogs

1969 ◽  
Vol 21 (02) ◽  
pp. 294-303 ◽  
Author(s):  
H Mihara ◽  
T Fujii ◽  
S Okamoto
Keyword(s):  
Cerebrospinal Fluid ◽  
Carboxylic Acid ◽  
Fibrinolytic Activity ◽  
Clinical Implications ◽  
Trans Form ◽  
Plate Method ◽  
Blood Samples ◽  
Fibrin Plate ◽  
The Brain

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.

Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease

2009 ◽  
Vol 150 (46) ◽  
pp. 2101-2109 ◽  
Author(s):  
Péter Csécsei ◽  
Anita Trauninger ◽  
Sámuel Komoly ◽  
Zsolt Illés
Keyword(s):  
Neuromyelitis Optica ◽  
Water Channel ◽  
Diagnostic Procedures ◽  
Diagnosis And Treatment ◽  
Clinical Settings ◽  
Permanent Disability ◽  
Therapeutic Decisions ◽  
Novel Concept ◽  
The Brain

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

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