Abstract
Purpose :
Early life stress (ELS) is defined as a period of severe and/or chronic trauma, as well as environmental/social deprivation or neglect in pre/early postnatal stage. Presently, the impact of ELS on the visual system in the adult stage is unknown. Using an animal model of maternal separation with early weaning (MSEW), which mimics early life neglect, we analyzed the long-term ELS consequences on the visual system.
Methods :
Male and female C57BL/6 mice were separated from the dams for 2 h at postnatal days (PNDs) 2-5, for 3 h at PNDs 7-9, for 4 h at PNDs 10-13, for 6 h at PNDs 14-16, and weaned at PND17. At the end of each separation period, mothers were subjected to movement restriction for 10 min. Control pups were left undisturbed from PND0, and weaned at PND21. Electroretinograms (ERG), visual evoked potentials (VEP), vision-guided behavioral tests (looming and virtual cliff tests), retinal anterograde transport (intravitreal cholera toxin β-subunit), and retinal histopathology (by immunohistochemistry) were examined in adult mice. Corticosterone levels were assessed by RIA. One group of animals received 10 mg/kg mifepristone (injected every 3 days between PNDs 4-16) or vehicle.
The statistical analysis was performed using R statistical software, and “lme4” package was used for linear mixed models. Groups (control or MSEW), treatments (vehicle or Mifepristone) and sex, were used as fixed effects. Litter was used as random effect. ANOVA followed by Tukey’s HSD test was performed.
Results :
MSEW induced long-lasting functional and histological effects at retinal level, including decreased inner (but not outer) plexiform layer synaptophysin content (P<0.01), Iba-1(+) cell density (P<0.01) and soma size (P<0.01), decreased retinal ganglion cell (RGC) function (P<0.01), VEP amplitude (P<0.001) retina-superior colliculus communication (P<0.05), and RGC loss (P<0.001), but not the ERG a- and b-wave amplitude. These alterations translated into deficits in vision-guided behaviors. MSEW increased corticosterone levels at PND10. Mifepristone treatment prevented functional and structural MSEW-induced alterations in adult mice.
Conclusions :
These results suggest that retinal alterations might be included among the childhood adversity-induced threats to life quality, which could be prevented by an early pharmacological intervention with mifepristone.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.