Retinotectal plasticity induced by monocular enucleation during the critical period is dependent of A2a adenosine receptor: A possible role of astrocytes.

The retinotectal topography of rats develops within the first three postnatal weeks during the critical period. Previous studies have shown that monocular enucleation results in plasticity of the intact retinotectal pathway in a time-dependent manner. Glial fibrillary acidic protein (GFAP), an astrocyte marker, is up-regulated after central nervous system injury. Adenosine is a neuromodulator involved in the development and plasticity of the visual system acting through the inhibitory A1 and excitatory A2a receptor activities. Herein, we examined whether adenosine receptors and astrocytes are crucial for monocular enucleation (ME)-induced plasticity. We also investigate whether A2a blockade alters retinotectal plasticity in an astrocyte-dependent manner. Lister Hooded rats were submitted to monocular enucleation at postnatal day 10 (PND10) or PND21 and, after different survival times, were processed for immunohistochemistry or western blotting assays. Another group underwent subpial implantation of ELVAX containing vehicle (DMSO) or SCH58261 (1 µM - an A2a receptor antagonist), simultaneously with ME at PND10. After a 72 h survival, GFAP content and the retinotectal plasticity were evaluated. Our data show that monocular enucleation leads to an upregulation in GFAP expression in the contralateral superior colliculus. At PND10, a slight increase in GFAP labeling was observed at 72 h post-enucleation, while at PND21 GFAP increase was detected in the deafferented superior colliculus after 1 to 3 weeks of survival. The content of adenosine receptors also varies in the contralateral target after ME. A transient increase in A1 receptors is observed in the early periods of plasticity, while A2a receptors are upregulated later. Interestingly, the local blockade of A2a receptors abolished the increase in GFAP and the retinotectal reorganization induced by monocular enucleation during the critical period. Taken together these results suggest a correlation between astrocytes and A2a adenosine receptors in the subcortical visual plasticity.

Enteric glial cell reactivity in colonic layers and mucosal modulation in a mouse model of Parkinson's disease induced by 6-hydroxydopamine.

Enteric glial cells (EGCs) constitute the majority of the neural population of the enteric nervous system and are found in all layers of the gastrointestinal tract. It is active in enteric functions such as immunomodulation, participating in inflammation and intestinal epithelial barrier (IEB) regulation. Both EGCs and IEB have been described as altered in Parkinson's disease (PD). Using an animal model of PD induced by 6-hydroxydopamine (6-OHDA), we investigated the effect of ongoing neurodegeneration on EGCs and inflammatory response during short periods after model induction. C57Bl/6 male mice were unilaterally injected with 6-OHDA in the striatum. Compared to the control group, 6-OHDA animals showed decreased relative water content in their feces from 1 w after model induction. Moreover, at 1 and 2 w post-induction, groups showed histopathological changes indicative of intestinal inflammation. We identified an increase in IBA1 and GFAP levels in the intestinal mucosa. At an earlier survival of 48 h, we detected an increase in GFAP in the neuromuscular layer, suggesting that it was a primary event for the upregulation of GDNF, TNF-α, and occludin in the intestinal mucosa observed after 1 w. Within 2 w, we identified a decrease in the expression of occludin barrier proteins. Thus, EGCs modulation may be an early enteric signal induced by parkinsonian neurodegeneration, followed by inflammatory and dysmotility signs besides IEB modification.

5/6 nephrectomy affects enteric glial cells and promotes impaired antioxidant defense in the colonic neuromuscular layer.

AIMS: Chronic kidney disease (CKD) produces multiple repercussions in the gastrointestinal tract (GIT), such as alterations in motility, gut microbiota, intestinal permeability, and increased oxidative stress. However, despite enteric glial cells (EGC) having important neural and immune features in GIT physiology, their function in CKD remains unknown. The present study investigates colonic glial markers, inflammation, and antioxidant parameters in a CKD model. MAIN METHODS: A 5/6 nephrectomized rat model was used to induce CKD in rats and Sham-operated animals as a control to suppress. Biochemical measures in plasma and neuromuscular layer such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were carried out. Kidney histopathology was evaluated. Colon morphology analysis and glial fibrillary acid protein (GFAP), connexin-43 (Cx43), nuclear factor-kappa B (NF-κB) p65, and GPx protein expression were performed. KEY FINDINGS: The CKD group exhibited dilated tubules and tubulointerstitial fibrosis in the reminiscent kidney (p = 0.0002). CKD rats showed higher SOD activity (p = 0.004) in plasma, with no differences in neuromuscular layer (p = 0.9833). However, GPx activity was decreased in the CKD group in plasma (p = 0.013) and neuromuscular layer (p = 0.0338). Morphological analysis revealed alterations in colonic morphometry with inflammatory foci in the submucosal layer and neuromuscular layer straightness in CKD rats (p = 0.0291). In addition, GFAP, Cx43, NF-κBp65 protein expression were increased, and GPx decreased in the neuromuscular layer of the CKD group (p < 0.05). SIGNIFICANCE: CKD animals present alterations in colonic cytoarchitecture and decreased layer thickness. Moreover, CKD affects the enteric glial network of the neuromuscular layer, associated with decreased antioxidant activity and inflammation.

High-fat diets on the enteric nervous system: Possible interactions and mechanisms underlying dysmotility.

Obesity is a chronic disease that affects various physiological systems. Among them, the gastrointestinal tract appears to be a main target of this disease. High-fat diet (HFD) animal models can help recapitulate the classic signs of obesity and present a series of gastrointestinal alterations, mainly dysmotility. Because intestinal motility is governed by the enteric nervous system (ENS), enteric neurons, and glial cells have been studied in HFD models. Given the importance of the ENS in general gut physiology, this review aims to discuss the relationship between HFD-induced neuroplasticity and gut dysmotility observed in experimental models. Furthermore, we highlight components of the gut environment that might influence enteric neuroplasticity, including gut microbiota, enteric glio-epithelial unit, serotonin release, immune cells, and disturbances such as inflammation and oxidative stress.

Brazil Nut (Bertholletia excelsa H.B.K) Retards Gastric Emptying and Modulates Enteric Glial Cells in a Dose-Dependent Manner.

BACKGROUND: The role of food and nutrients in the regulation of enteric glial cell functions is unclear. Some foods influence enteric neurophysiology and can affect glial cell functions that include regulation of the intestinal barrier, gastric emptying, and colonic transit. Brazil nuts are the most abundant natural source of selenium, unsaturated fatty acids, fibers, and polyphenols. OBJECTIVE: The study investigated the effects of a Brazil nut-enriched diet on enteric glial cells and gastrointestinal transit. METHODS: Two-month-old male Wistar rats were randomized to a standard diet (control group, CG), standard diet containing 5% (wt/wt) Brazil nut (BN5), and standard diet containing 10% (wt/wt) Brazil nut (BN10) (n = 9 per group). After eight weeks, the animals underwent constipation and gastric emptying tests to assess motility. Evaluations of colonic immunofluorescence staining for glial fibrillary acidic protein (GFAP) and myenteric ganglia area were performed. RESULTS: The BN5 group showed increased weight gain while the BN10 group did not (p < 0.0001). The BN10 group showed higher gastric residue amounts compared to the other groups (p = 0.0008). The colon exhibited an increase in GFAP immunoreactivity in the BN5 group compared to that in the other groups (p = 0.0016), and the BN10 group presented minor immunoreactivity compared to the CG (p = 0.04). The BN10 group presented a minor ganglia area compared to the CG (p = 0.0155). CONCLUSION: The Brazil nut-enriched diet modified the gastric residual, colonic GFAP immunoreactivity, and myenteric ganglia area after eight weeks in healthy male Wistar rats.

The enteric glia: identity and functions.

Enteric glial cells were first described at the end of the 19th century, but they attracted more interest from researchers only in the last decades of the 20th. Although, they have a different embryological origin, the enteric GLIA share many characteristics with astrocytes, the main glial cell type of the central nervous system (CNS), such as in their expression of the same markers and in their functions. Here we review the construction of the enteric nervous system (ENS), with a focus on enteric glia, and also the main studies that have revealed the action of enteric glia in different aspects of gastrointestinal tract homeostasis, such as in the intestinal barrier, in communications with neurons, and in their action as progenitor cells. We also discuss recent discoveries about the roles of enteric glia in different disorders that affect the ENS, such as degenerative pathologies including Parkinson's and prion diseases, and in cases of intestinal diseases and injury.