Corticotropin-releasing factor protects against ammonia neurotoxicity in isolated larval zebrafish brains [RESEARCH ARTICLE]

Tegan A. Williams and Nicholas J. Bernier The physiological roles of corticotropin-releasing factor (CRF) have recently been extended to cytoprotection. Here, to determine whether CRF is neuroprotective in fish, the effects of CRF against high environmental ammonia (HEA)-mediated neurogenic impairment and cell death were investigated in zebrafish. In vivo, exposure of 1 day post-fertilization (dpf) embryos to HEA only reduced the expression of the determined neuron marker, neurod1. In contrast, in 5 dpf larvae, HEA increased the expression of nes and sox2, neural progenitor cell markers, and reduced the expression of neurog1, gfap and mbpa, proneuronal cell, radial glia and oligodendrocyte markers, respectively, and neurod1. The N-methyl-D-aspartate (NMDA) receptor inhibitor MK801 rescued the HEA-induced reduction in neurod1 in 5 dpf larvae but did not affect the HEA-induced transcriptional changes in other neural cell types, suggesting that hyperactivation of NMDA receptors specifically contributes to the deleterious effects of HEA in determined neurons. As observed in vivo, HEA exposure elicited marked changes in the expression of cell-type specific markers in isolated 5 dpf larval brains. The addition of CRF reversed the in vitro effects of HEA on neurod1 expression and prevented an HEA-induced increase in cell death. Finally, the protective effects of CRF against HEA-mediated neurogenic impairment and cell death were prevented by the CRF type 1 receptor selective antagoni...
Source: Journal of Experimental Biology - Category: Biology Authors: Tags: RESEARCH ARTICLE Source Type: research