Abstract
Purpose :
Type II diabetes (modeled in this research with hyperglycemia) has been shown to cause cognitive deficits and lead to retinopathy. Here, we looked at adult zebrafish to see if breakdowns in the blood-brain barrier and the blood-retinal barrier would be correlated with dysfunction on vision- and/or memory-guided behavioral assays. We hypothesized that our glucose-treated fish would have increased inflammatory markers (Rel-A) and decreased tight junction protein (Claudin-5) in the brain and retina, and that these markers would be consistent with glucose-treated fish having inferior performance on vision- and memory-guided assays.
Methods :
To test our hypothesis, we maintained three groups of fish (roughly 10 per group), water-treated (stress control), mannitol-treated (osmotic control) and glucose-treated, in hyperglycemic conditions (or control) for 8 or 12 weeks while we collecting behavioral data. Every four weeks, fish were run through a three-chamber choice task (3CC) to assess cognition and, at the end of exposure, visually guided optomotor responses (OMR) were assessed and tissue samples were collected to determine changes in brain and retinal protein levels.
Results :
At 8 weeks, no significant changes to memory were observed in glucose-treated fish. At 12 weeks, glucose-treated fish had significantly improved memory relative to water-treated fish (p < 0.001), though they were not significantly different from mannitol-treated fish. OMRs at 8 weeks revealed that glucose-treated fish performed better than both mannitol- (p = 0.0166) and water-treated fish (p = 0.0394). At 12 weeks, significantly more glucose-treated fish displayed positive OMRs compared to mannitol-treated controls (p = 0.0166). Preliminary molecular results show increased Rel-A and decreased Claudin-5 in both the brain and the retina of glucose-treated fish at both time points.
Conclusions :
These results suggest that hyperglycemia-induced deficits in vision and cognition are controlled by different pathways; one involving osmotically-induced alterations and the other initiated by glucose specific mechanisms. Overall, hyperglycemia induced inflammation and decreased tight junction proteins seemed to be correlated with better performance on vision and memory guided behavioral assays.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.