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.

Chronic social defeat stress differentially regulates the expression of BDNF transcripts and epigenetic modifying enzymes in susceptible and resilient mice

Mallei, Alessandra;Ieraci, Alessandro
;
2018-01-01

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11389/43875
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