Alessandra Mallei1, Alessandro Ieraci1, Maurizio Popoli1. 1. Laboratory of Neuropsychopharmacology and Functional Neurogenomics - Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases, University of Milano, Milano, Italy.
Abstract
Objectives: Although stress is considered a primary risk factor for neuropsychiatric disorders, a majority of individuals are resilient to the effects of stress exposure and successfully adapt to adverse life events, while others, the so-called susceptible individuals, may have problems to properly adapt to environmental changes. However, the mechanisms underlying these different responses to stress exposure are poorly understood. Methods: Adult male C57BL/6J mice were exposed to chronic social defeat stress protocol and levels of brain derived neurotrophic factor (BDNF) transcripts and epigenetic modifying enzymes were analysed by real-time PCR in the hippocampus (HPC) and prefrontal cortex (PFC) of susceptible and resilient mice. Results: We found a selective reduction of BDNF-6 transcript in the HPC and an increase of BDNF-4 transcript in the PFC of susceptible mice. Moreover, susceptible mice showed a selective reduction of the g9a mRNA levels in the HPC, while HDAC-5 and DNMT3a mRNA levels were specifically reduced in the PFC.Conclusions: Overall, our results, showing a different expression of BDNF transcripts and epigenetic modifying enzymes in susceptible and resilient mice, suggest that stress resilience is not simply a lack of activation of stress-related pathways, but is related to the activation of additional different specific mechanisms.
Objectives: Although stress is considered a primary risk factor for neuropsychiatric disorders, a majority of individuals are resilient to the effects of stress exposure and successfully adapt to adverse life events, while others, the so-called susceptible individuals, may have problems to properly adapt to environmental changes. However, the mechanisms underlying these different responses to stress exposure are poorly understood. Methods: Adult male C57BL/6J mice were exposed to chronic social defeat stress protocol and levels of brain derived neurotrophic factor (BDNF) transcripts and epigenetic modifying enzymes were analysed by real-time PCR in the hippocampus (HPC) and prefrontal cortex (PFC) of susceptible and resilient mice. Results: We found a selective reduction of BDNF-6 transcript in the HPC and an increase of BDNF-4 transcript in the PFC of susceptible mice. Moreover, susceptible mice showed a selective reduction of the g9a mRNA levels in the HPC, while HDAC-5 and DNMT3a mRNA levels were specifically reduced in the PFC.Conclusions: Overall, our results, showing a different expression of BDNF transcripts and epigenetic modifying enzymes in susceptible and resilient mice, suggest that stress resilience is not simply a lack of activation of stress-related pathways, but is related to the activation of additional different specific mechanisms.