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.

Expression of GAP-43 during development and after monocular enucleation in the rat superior colliculus.

The retinotectal projection of rodents presents a precise retinotopic organization that develops, from diffuse connections, from the day of birth to post-natal day 10. Previous data had demonstrated that these projections undergo reorganization after retinal lesions, nerve crush and monocular enucleation. The axonal growth seems to be directly related to growth-associated protein-43 (GAP-43) expression, a protein predominantly located in growth cones, which is regulated throughout development. GAP-43 is presented both under non-phosphorylated and phosphorylated (pGAP-43) forms. The phosphorylated form, has been associated to axon growth via polymerization of F-actin, and synaptic enhancement through neurotransmitter release facilitation. Herein we investigated the spatio-temporal expression of GAP-43 in the rat superior colliculus during normal development and after monocular enucleation in different stages of development. Lister Hooded rats ranging from post-natal day 0 to 70 were used for ontogeny studies. Another group of animals were submitted to monocular enucleation at post-natal day 10 (PND10) or PND21. After different survival-times, the animals were sacrificed and the brains processed for either immunohistochemistry or western blotting analysis. Our data show that GAP-43 is expressed in retinotectal axons in early stages of development but remains present in adulthood. Moreover, monocular enucleation leads to an increase in pGAP-43 expression in the deafferented colliculus. Taken together these results suggest a role for pGAP-43 in retinotectal morphological plasticity observed both during normal development and after monocular enucleation.