Disorders of the Nervous System
Author: Salvador Calanni | Email: salvadorcalanni@gmail.com
Juan Salvador Calanni1°, Laura Andrea Pasquini2°,Nathaly Bernal Aguirre1°, Damian Dorfman1°, Ruth Estela Rosenstein1°
1° Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, IQUIBICEN, FCEN-UBA, CONICET
2° IQUIFIB, FFyB-UBA, CONICET
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/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), we analyzed the long-term ELS consequences in the visual system.
Mice were separated from the dams for 2 h at postnatal days (PNDs) 4-6, 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. Control pups were left undisturbed from PND0, and weaned at PND21. At PND 60-75, MSEW did not affect the electroretinogram a- and b-wave amplitude, but decreased retinal ganglion cell (RGC) function and number, and increased retinal Iba-1(+) area, and cell soma size, consistently with an increased number of amoeboid microglial cells. At PND45 microgliosis preceded RGC loss, supporting a key role of microglia in visual function alterations induced by ELS. To investigate this hypothesis, microglial depletion was induced by a treatment with Sotuletinib, a Colony Stimulating Factor Receptor inhibitor, orally and daily administered from PND35 to PND60. Sotuletinib alone did not affect the number or function of RGCs, but it significantly mitigated RGC function and number loss in MSEW mice at PND 60.
In summary, our results suggest that microglial cells could play a key role in long term consequences of early life stress on the visual system of mice.