California sea lions (CSLs) exposed to the marine biotoxin
domoic acid (DA) develop an acute or chronic toxicosis marked by
seizures and act as sentinels of the disease. Experimental evidence suggests that oxidative stress and
neuroinflammation are important mechanisms underlying the seizurogenic potential of environmental toxicants but these pathways are relatively unstudied in CSLs. In the current study, we investigated the role of
glutamate-
glutamine changes and
gliosis in DA-exposed CSLs to better understand the neurotoxic mechanisms occurring during DA toxicity. Sections from archived hippocampi from control and CSLs diagnosed with DA toxicosis were immunofluorescently stained for markers of
gliosis, oxidative/nitrative stress and changes in
glutamine synthetase (GS). Quantitative assessment revealed increasing loss of microtubule associated protein-2 positive neurons with elevations in
4-hydroxynonenal correlating with chronicity of exposure, whereas the pattern of activated glia expressing
nitric oxide synthase 2 and
tumor necrosis factor followed pathological severity. There was no significant change in the amount of GS positive cells but there was increased
3-nitrotyrosine in GS expressing cells and in neurons, particularly in animals with chronic DA toxicosis. These changes were consistently seen in the dentate gyrus and in the cornu ammonis (CA) sectors CA3, CA4, and CA1. The results of this study indicate that
gliosis and resultant changes in GS are likely important mechanisms in DA-induced seizure that need to be further explored as potential
therapies in treating exposed wildlife.