Interferon Signaling After TBI in Aged Mice

Type I Interferons (IFN-I) contribute to the neuropathology of traumatic brain injury (TBI) and age-related neurodegenerative disease, where Cyclic GMP-AMP Synthase (cGAS) and the Stimulator of Interferon Genes (STING) pathway are implicated as key inducers of IFN-I responses. This study evaluated cGAS/STING activation, IFN-I signaling and neuroinflammation in the cortex and hippocampus of young and aged C57Bl/6 male mice, 24 hrs after controlled cortical impact injury. TBI increased expression of transcripts related to IFN-I signaling and activation of cGAS in the injured cortex of aged mice compared to younger mice. These observations were confirmed by RT-PCR, western blotting and phosphorylation/activation of STAT1, a downstream IFN-I effector molecule Young (3 month-old) and aged (22 month-old) adult male C57Bl/6 mice (National Institute of Aging colony, Charles River Laboratories) were housed under a 12 hour light-dark cycle, with ad libitum access to food and water. Under an approved Institutional Animal Care and Use Committee protocol, mice were anesthetized and subjected to mild controlled cortical impact, or identical preparation with no injury (sham). Twenty-four hours later, mice were re-anesthetized, perfused with 0.9% saline (100 ml), and ipsilateral cortical and hippocampal tissues were removed and frozen in liquid nitrogen for RNA or protein extraction. Study groups (n=6, for each) were: young sham, young TBI, aged sham, and aged TBI. One sample from the 3 month injured group was not included in the dataset/study as it did not meet NanoString quality control metrics.