|GURURAJAN, ANAND - University College Cork|
|VAN DE WOUW, MARCEL - University College Cork|
|BOEHME, MARCUS - University College Cork|
|BECKER, THORSTEN - University College Cork|
|O'CONNOR, RORY - University College Cork|
|BASTIAANSSEN, THOMAZ - University College Cork|
|MOLONEY, GERARD - University College Cork|
|Lyte, Joshua - Josh|
|VENTURA SILVA, ANA - University College Cork|
|MERCKX, BARBARA - University College Cork|
|DINAN, TIMOTHY - University College Cork|
|CRYAN, JOHN - University College Cork|
Submitted to: Brain Behavior and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2019
Publication Date: 8/1/2019
Citation: Gururajan, A., Van De Wouw, M., Boehme, M., Becker, T., O'Connor, R., Bastiaanssen, T.F., Moloney, G.M., Lyte, J.M., Ventura Silva, A.P., Merckx, B., Dinan, T.G., Cryan, J.F. 2019. Resilience to chronic stress is associated with specific neurobiological, neuroendocrine and immune responses. Brain Behavior and Immunity. 80:583-594. https://doi.org/10.1016/j.bbi.2019.05.004.
Interpretive Summary: Chronic stress is related to the development of depression, anxiety, and other mental health issues prevalent in society. Understanding how individuals react to stress may help scientists better understand how chronic stress can lead to such mental health problems, and therefore provide clues in the development of therapeutics that prevent stress-induced mental illnesses. Using a mouse model of chronic stress, we sought to determine which mice were susceptible to chronic stress and which mice were resilient to chronic stress, and identify physiological responses that were unique to either the stress-susceptible or stress-resilient groups. We found several biological responses, including some related to the hormonal and immune systems, that were associated with stress susceptibility or resilience in mice. Our results may help to provide potential targets for future studies that seek to develop therapeutics to address susceptibility to stress.
Technical Abstract: Research into the molecular basis of stress resilience is a novel strategy to identify potential therapeutic strategies to treat stress-induced psychopathologies such as anxiety and depression. Stress resilience is a phenomenon which is not solely driven by effects within the central nervous system (CNS) but involves multiple systems, central and peripheral, which interact with and influence each other. Accordingly, we used the chronic social defeat stress paradigm and investigated specific CNS, endocrine and immune responses to identify signatures of stress-resilience and stress susceptibility in mice. Our results showed that mice behaviourally susceptible to stress (indexed by a reduction in social interaction behaviour) had higher plasma corticosterone levels and adrenal hypertrophy. An increase in inflammatory circulating monocytes was another hallmark of stress susceptibility. Furthermore, prefrontal cortex mRNA expression of corticotrophin-releasing factor (Crf) was increased in susceptible mice relative to resilient mice. We also report differences in hippocampal synaptic plasticity between resilient and susceptible mice. Ongoing studies will interpret the functional relevance of these signatures which could potentially inform the development of novel psychotherapeutic strategies.