Early life selective knockdown of the TrkB receptor and maternal separation modulates adult stress phenotype
Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been implicated in mood and anxiety disorders and is upregulated by antidepressants. It has marked effects on synaptic and extra-synaptic plasticity through tropomyosin receptor kinase B (TrkB). Importantly, early life stressors that affect BDNF production are known to predispose individuals towards the later development of depression or anxiety disorders. Yet, few studies have actually assessed the long-term impact of selective early life BDNF manipulation. Therefore, we utilized a knock-in transgenic mouse line (TrkBF616A) with a mutation on the full-length TrkB receptor (TrkB.tk+), to reversibly block early postnatal BDNF/TrkB signaling. This was done during exposure to early life stress (maternal separation) followed by exposure to 35 days of chronic unpredictable stress (CUS) in adulthood. The TrkB.tk + mice that received the stressor treatments displayed a blunted anhedonic-like response (sucrose preference), compared to stressed animals that did not have the transient early life TrkB knockdown. But the TrkB.tk + mice actually showed an enhanced anxiety-like response in an open field in response following the CUS. This was paralleled by reductions of BDNF within the PFC and hippocampus of stressed TrkB.tk + mice, but basal elevations of BDNF was evident in the nucleus accumbens. These data are consistent with the contention that early in life, BDNF may program stress responsive circuits but this may differentially map onto depressive and anxiety-like responses in adulthood.
|Keywords||Anxiety, Chronic stress, Early life stress, ELS, NTRK2, Receptor tyrosine kinase, TrkB|
|Journal||Behavioural Brain Research|
Prowse, N. (N.), Dwyer, Z. (Z.), Thompson, A. (A.), Fortin, T. (T.), Elson, K. (K.), Robeson, H. (H.), … Hayley, S. (2020). Early life selective knockdown of the TrkB receptor and maternal separation modulates adult stress phenotype. Behavioural Brain Research, 378. doi:10.1016/j.bbr.2019.112260