Title : Pre-exposure to acute stress modulates the molecular response to a mild traumatic brain injury
Stress is generally defined as a real or interpreted threat to the psychological or physiological integrity of an individual that results in physiological and/or behavioral responses. Threatening stimuli trigger neuronal responses in the brain that cause an immediate adaptive systemic reaction, including the activation of (1) the hypothalamus-pituitary-adrenal axis; (2) the autonomic nervous system; (3) distinct classes of genes (e.g. immediate early genes, regeneration associated genes). Here we investigate potential interactions between two different stress stimuli, namely acute restraint stress (AS; psychological integrity) and mild traumatic brain injury (TBI; physiological integrity), in an in vivo mouse model. Therefore, mice were either exposed to 45 minutes of restraint stress, followed by a mild TBI/Sham-operation; or only received a TBI/Sham-operation.
At 1h post injury, we observed, that a single exposure to AS is sufficient to dampen the gene-expression response after TBI not only in different brain regions (cortex, hippocampus, amygdala), but also in varying peripheral organs (pituitary gland, adrenal gland, heart, spleen).
Previously, the transcription factor Activating Transcription Factor 3 (Atf3) has been demonstrated to play a crucial role in neuroprotective functions in injury of the peripheral nervous system and in processing of stress and cellular damage in the central nervous system. Here we show, that Atf3 is a key regulator of the gene response in the pituitary gland, adrenal gland and heart, as constitutive Atf3-mutant animals neither respond to AS, TBI nor the combination of both stressors. Furthermore, Atf3KO animals showed higher mortality rates directly after TBI and more severe behavioral limitations (neurological severity score).
Overall, our data shows that a pre-exposure to AS does affect short-term outcomes after TBI.
What will audience learn from your presentation?
- The interaction and influence of two stressors of different nature
- Greater understanding of the impact of a traumatic brain injury on peripheral organs
- The role of activating transcription factor 3 (Atf3) as an adaptive and protective factor during/following injury