Digesting the emerging role for the gut microbiome in central nervous system demyelination

2014 ◽  
Vol 20 (12) ◽  
pp. 1553-1559 ◽  
Author(s):  
Jennifer Joscelyn ◽  
Lloyd H Kasper

The fields of microbiology, immunology, neurology and nutrition are rapidly converging, as advanced sequencing and genomics-based methodologies have enabled the mapping out of the microbial diversity of humans for the first time. Bugs, guts, brains and behavior were once believed to be separate domains of clinical practice and research; however, recent observations in our understanding of the microbiome indicate that the boundaries between domains are becoming permeable. This permeability is multidirectional: Biological systems are operating simultaneously in a vastly complex and interconnected web. Understanding the microbiome-gut-brain axis will entail fleshing out the mechanisms by which transduction across each domain occurs, allowing us ultimately to appreciate the role of commensal organisms in shaping and modulating host immunity. This article will highlight animal and human research to date, as well as highlight directions for future research. We speculate that the gut microbiome is potentially the premier environmental risk factor mediating inflammatory central nervous system demyelination, in particular multiple sclerosis.

Author(s):  
Rohit Joshi ◽  
Rashmi Sipani ◽  
Asif Bakshi

Hox genes have been known for specifying the anterior-posterior axis (AP) in bilaterian body plans. Studies in vertebrates have shown their importance in developing region-specific neural circuitry and diversifying motor neuron pools. In Drosophila, they are instrumental for segment-specific neurogenesis and myogenesis early in development. Their robust expression in differentiated neurons implied their role in assembling region-specific neuromuscular networks. In the last decade, studies in Drosophila have unequivocally established that Hox genes go beyond their conventional functions of generating cellular diversity along the AP axis of the developing central nervous system. These roles range from establishing and maintaining the neuromuscular networks to controlling their function by regulating the motor neuron morphology and neurophysiology, thereby directly impacting the behavior. Here we summarize the limited knowledge on the role of Drosophila Hox genes in the assembly of region-specific neuromuscular networks and their effect on associated behavior.


Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4205-4218 ◽  
Author(s):  
Torsten Bossing ◽  
Andrea H. Brand

Ephrin/Eph signalling is crucial for axonal pathfinding in vertebrates and invertebrates. We identified the Drosophila ephrin orthologue, Dephrin, and describe for the first time the role of ephrin/Eph signalling in the embryonic central nervous system (CNS). Dephrin is a transmembrane ephrin with a unique N terminus and an ephrinB-like cytoplasmic tail. Dephrin binds and interacts with DEph, the Drosophila Eph-like receptor, and Dephrin and DEph are confined to different neuronal compartments. Loss of Dephrin or DEph causes the abberant exit of interneuronal axons from the CNS, whereas ectopic expression of Dephrin halts axonal growth. We propose that the longitudinal tracts in the Drosophila CNS are moulded by a repulsive outer border of Dephrin expression.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yiyang Zheng ◽  
Yanyan Luo ◽  
Xixi Chen ◽  
Huiting Li ◽  
Baojun Huang ◽  
...  

AbstractNeural tumors can generally be divided into central nervous system tumors and peripheral nervous tumors. Because this type of tumor is located in the nerve, even benign tumors are often difficult to remove by surgery. In addition, the majority of neural tumors are malignant, and it is particular the same for the central nervous system tumors. Even treated with the means such as chemotherapy and radiotherapy, they are also difficult to completely cure. In recent years, an increasingly number of studies have focused on the use of mRNA to treat tumors, representing an emerging gene therapy. The use of mRNA can use the expression of some functional proteins for the treatment of genetic disorders or tissue repair, and it can also be applied to immunotherapy through the expression of antigens, antibodies or receptors. Therefore, although these therapies are not fully-fledged enough, they have a broad research prospect. In addition, there are many ways to treat tumors using mRNA vaccines and exosomes carrying mRNA, which have drawn much attention. In this study, we reviewed the current research on the role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors, and examine the future research prospects of mRNA in neural tumors and the opportunities and challenges that will arise in the future application of clinical treatment.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ana Ghenciulescu ◽  
Rebecca J. Park ◽  
Philip W. J. Burnet

The human gut microbiome is emerging as a key modulator of homeostasis, with far-reaching implications for various multifactorial diseases, including anorexia nervosa (AN). Despite significant morbidity and mortality, the underlying mechanisms of this eating disorder are poorly understood, but the classical view defining AN as a purely psychiatric condition is increasingly being challenged. Accumulating evidence from comparative studies of AN and healthy fecal microbial composition reveals considerable low divergence and altered taxonomic abundance of the AN gut microbiome. When integrated with preclinical data, these findings point to a significant role of the gut microbiome in AN pathophysiology, via effects on host energy metabolism, intestinal permeability, immune function, appetite, and behavior. While complex causal relationships between genetic risk factors, dietary patterns and microbiome, and their relevance for AN onset and perpetuation have not been fully elucidated, preliminary clinical studies support the use of microbiome-based interventions such as fecal microbiota transplants and probiotics as adjuvants to standard AN therapies. Future research should aim to move from observational to mechanistic, as dissecting how specific microbial taxa interact with the host to impact the development of AN could help design novel therapeutic approaches that more effectively address the severe comorbidities and high relapse rate of this serious disorder.


2012 ◽  
Vol 12 (3-4) ◽  
pp. 235-248
Author(s):  
Peter Oliver Behan ◽  
Abhijit Chaudhuri ◽  
Simone Hutchinson

An important legal question is the role of acute trauma on the central nervous system with stress in precipitating or worsening multiple sclerosis (MS). At present, the prevailing view in neurology is that there is no relationship. We show here that this opinion needs to be reappraised. Medicolegal decisions for compensation in court have hinged on this question, as do the future research and treatment. A critical analysis of highly important but hitherto neglected articles shows the prevailing view to be gravely mistaken. Modern molecular medicine has shown conclusively that trauma and stress (either alone or together) to the central nervous system cause disruption of the blood–brain barrier (BBB). Disruption of this BBB, a complex molecular process, is the basic pathological feature of MS and is affected in both trauma and stress. Its further study should lead to a rational mode of therapy and resolve the legal quagmire.


2006 ◽  
Vol 168 (5) ◽  
pp. 1464-1473 ◽  
Author(s):  
Paula Maña ◽  
David Liñares ◽  
Sue Fordham ◽  
Maria Staykova ◽  
David Willenborg

1996 ◽  
Vol 1 (1) ◽  
pp. 51-57
Author(s):  
Michael D Boissevan

This article reviews four areas of psychological research in fibromyalgia. First, the literature on depression in fibromyalgia shows that although the preponderance of studies demonstrate that fibromyalgia patients are more depressed than comparable medical patients, rigorous disconfirming evidence exists. Thus the role of depression in fibromyalgia remains unclear because consistent levels of depression are not found either between samples or between subjects. Second, the role of pain perception in fibromyalgia shows that fibromyalgia patients are consistently more responsive to aversive stimulation than other subjects with chronic pain. This pattern of hyper-responsiveness appears to be generalized, rather than localized to tender points. These results are discussed in terms of potential central nervous system mechanisms. Third, original research in clinical cognitive psychology is presented that shows that fibromyalgia patients do not appear to demonstrate cognitive biases which are distinct from myofascial pain. Although extremely preliminary, these results argue against a unique psychological explanation for fibromyalgia symptoms. Fourth, neuropsychological research demonstrates a pattern of generalized inhibition of information processing that emulates that observed in depressive illness, except that fibromyalgia patients tend not to show the compromise in right hemisphere processing seen in depression. This suggests that cognitive abnormalities in fibromyalgia may be distinct from those seen in depression. The psychological research reviewed suggests that central nervous system anomalies may be implicated in the syndrome of fibromyalgia, but the evidence for motivated or affective psychological involvement in the syndrome remains equivocal. Suggestions are provided for future research.


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