Stool Glial Fibrillary Acidic Protein Is Elevated in Progressive Multiple Sclerosis.

Objectives: The gut microbiota and altered intestinal physiology have been implicated in multiple sclerosis (MS). Enteric glial cells regulate enteric nervous and immune function and express glial fibrillary acidic protein (GFAP) and S100β. Serum GFAP and neurofilament light chain can predict disease worsening; however, no clear markers differentiate relapsing from progressive disease.

Faecal mucoprotein MUC2 is decreased in multiple sclerosis and is associated with mucin degrading bacteria.

Background: The gut microbiome is altered in MS and may contribute to disease by disrupting the intestinal barrier. The colonic mucus barrier, which is primarily composed of mucin protein 2 (MUC2), plays a crucial role in providing a barrier between colonic epithelial cells and the microbiome. Disruption of intestinal epithelial and mucus barriers has been reported in inflammatory bowel disease (IBD) and Parkinson's disease (PD) but has not been studied in the context of the microbiome in multiple sclerosis (MS).

Gut neuropeptide involvement in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder affecting over 10 million people. A key pathological feature of PD is the accumulation of misfolded α-synuclein (aSyn) protein in the substantia nigra pars compacta. Aggregation of aSyn can form Lewy bodies that contribute to dopaminergic neuron degeneration and motor symptoms, such as tremor, rigidity, and bradykinesia.

Sex Specific Effects of Environmental Toxin-Derived Alpha Synuclein on Enteric Neuronal-Epithelial Interactions.

Background: Parkinson's Disease (PD) is a neurodegenerative disorder with prodromal gastrointestinal (GI) issues often emerging decades before motor symptoms. Pathologically, PD can be driven by the accumulation of misfolded alpha synuclein (aSyn) protein in the brain and periphery, including the GI tract. Disease epidemiology differs by sex, with men twice as likely to develop PD.

Gut microbiota and metabolites are linked to disease progression in multiple sclerosis.

Progressive multiple sclerosis (MS) is a neurological disease with limited understanding of the biology associated with transition from relapsing to progressive disease. Intestinal microbes and metabolites are altered in MS, but relation to disease progression is largely unknown. We investigate microbiota and metabolites in subjects with stable MS, those who worsened, and in those with relapsing MS who became progressive over 2 years.

Akkermansia mono-colonization modulates microglia and astrocytes in a strain specific manner.

Microglia and astrocytes are the primary glial cells in the central nervous system (CNS) and their function is shaped by multiple factors. Regulation of CNS glia by the microbiota have been reported, although the role of specific bacteria has not been identified. We colonized germ-free mice with the type strain Akkermansia muciniphila (Am) and a novel A.

Maternal immune activation by toll-like receptor 7 agonist during mid-gestation increases susceptibility to blood-brain barrier leakage after puberty.

Maternal immune activation (MIA), a maternal stressor, increases risk for neuropsychiatric diseases, such as Major Depressive Disorder in offspring. MIA of toll-like receptor 7 (TLR7) initiates an immune response in mother and fetuses in a sex-selective manner. The paraventricular nucleus of the hypothalamus (PVN), a brain region that is sexually dimorphic and regulates hypothalamic-pituitary-adrenal (HPA) stress responses, have been tied to stress-related behaviors (i.

Sex specific effects of environmental toxin-derived alpha synuclein on enteric neuronal-epithelial interactions.

Background: Parkinson's Disease (PD) is a neurodegenerative disorder with prodromal gastrointestinal (GI) issues often emerging decades before motor symptoms. Pathologically, PD can be driven by accumulation of misfolded alpha synuclein (aSyn) protein in the brain and periphery, including the GI tract. Disease epidemiology differs by sex, with men twice as likely to develop PD.

Unraveling the physiology of the autonomic nervous system: An unlikely collaboration between Arturo Rosenblueth and Walter Cannon.

This article details the collaboration between Dr Walter B. Cannon (1871-1945) and Dr Arturo Rosenblueth (1900-1970) at the Department of Physiology at Harvard Medical School (HMS) in the 1930s-1940s. Cannon was a renowned physiologist whose Department of Physiology was home to scientists from around the globe.

H-NMR Profiling of Short-Chain Fatty Acid Content from a Physiologically Accurate Gut-on-a-Chip Device.

It has been shown that short-chain fatty acids (SCFAs) produced by the gut microbiome are of importance to host tissue health; however, measuring such compounds in biological samples is often limited to using hours to days old fecal and blood plasma samples. Organ-on-a-chip models have been created to simplify the complexity but struggle to reproduce the full biology of the gut specifically. We recently reported a tissue-in-a-chip gut model that incorporates gut explanted tissue into a microfluidic device.

Sex differences in anatomic plasticity of gut neuronal-mast cell interactions.

The gut wall houses mast cells that are anatomically situated near enteric neuronal fibers. Roles of specific neuropeptides in modulating function of immune components like mast cells in response to challenge with bacterial components are relatively unknown. Investigating such interactions requires models that include diverse cellular elements in native anatomic arrangements.

Vasoactive intestinal peptide regulates ileal goblet cell production in mice.

Innervation of the intestinal mucosa has gained more attention with demonstrations of tuft and enteroendocrine cell innervation. However, the role(s) these fibers play in maintaining the epithelial and mucus barriers are still poorly understood. This study therefore examines the proximity of mouse ileal goblet cells to neuronal fibers, and the regulation of goblet cell production by vasoactive intestinal peptide (VIP).

Human colon function ex vivo: Dependence on oxygen and sensitivity to antibiotic.

Background: Human intestines contain a heterogeneous collection of cells that include immune, neural and epithelial elements interacting in a highly complex physiology that is challenging to maintain ex vivo. There is an extreme oxygen gradient across the intestinal wall due in part to microbiota in the lumen and close to the gut wall, which complicates the design of tissue culture systems. The current study established the use of an organotypic slice model of human intestinal tissue derived from colonoscopy biopsies to study host-microbial interactions after antibiotic treatment, and the influence of oxygen concentration on gut wall function.

From organotypic culture to body-on-a-chip: A neuroendocrine perspective.

The methods used to study neuroendocrinology have been as diverse as the discoveries to come out of the field. Maintaining live neurones outside of a body in vitro was important from the beginning, building on methods that dated back to at least the first decade of the 20th Century. Neurosecretion defines an essential foundation of neuroendocrinology based on work that began in the 1920s and 1930s.

Powering ex vivo tissue models in microfluidic systems.

This Frontiers review analyzes the rapidly growing microfluidic strategies that have been employed in attempts to create physio relevant 'organ-on-chip' models using primary tissue removed from a body (human or animal). Tissue harvested immediately from an organism, and cultured under artificial conditions is referred to as ex vivo tissue. The use of primary (organotypic) tissue offers unique benefits over traditional cell culture experiments, and microfluidic technology can be used to further exploit these advantages.

An organotypic slice model for ex vivo study of neural, immune, and microbial interactions of mouse intestine.

Organotypic tissue slices provide seminatural, three-dimensional microenvironments for use in ex vivo study of specific organs and have advanced investigative capabilities compared with isolated cell cultures. Several characteristics of the gastrointestinal tract have made in vitro models for studying the intestine challenging, such as maintaining the intricate structure of microvilli, the intrinsic enteric nervous system, Peyer's patches, the microbiome, and the active contraction of gut muscles. In the present study, an organotypic intestinal slice model was developed that allows for functional investigation across regions of the intestine.