Prefrontal cortical trkB, glucocorticoids, and their interactions in stress and developmental contexts

Abstract

The tropomyosin/tyrosine receptor kinase B (trkB) and glucocorticoid receptor (GR) regulate neuron structure and function and the hormonal stress response. Meanwhile, disruption of trkB and GR activity (e.g., by chronic stress) can perturb neuronal morphology in cortico-limbic regions implicated in stressor-related illnesses like depression. Further, several of the short- and long-term neurobehavioral consequences of stress depend on the developmental timing and context of stressor exposure. We review how the levels and activities of trkB and GR in the prefrontal cortex (PFC) change during development, interact, are modulated by stress, and are implicated in depression. We review evidence that trkB- and GR-mediated signaling events impact the density and morphology of dendritic spines, the primary sites of excitatory synapses in the brain, highlighting effects in adolescents when possible. Finally, we review the role of neurotrophin and glucocorticoid systems in stress-related metaplasticity. We argue that better understanding the long-term effects of developmental stressors on PFC trkB, GR, and related factors may yield insights into risk for chronic, remitting depression and related neuropsychiatric illnesses.

Keywords: BDNF; Corticosterone; Cortisol; Dendritic spine; Juvenile; Neurotrophin; Tropomyosin receptor kinase; Tyrosine kinase receptor type 2.

Figure 1.. A graphical summary of developmental changes in trkB.FL and BDNF in human DLPFC.

(A) Levels of full-length trkB (TRKB.FL) mRNA in layers III and V reported by Romanczyk et al. (2002) and TRKB.FL mRNA reported by Luberg et al. (2010). trkB.FL protein levels reported by Luberg et al. (2010). (B) Levels of BDNF mRNA alternative transcripts containing exons II and IV reported by Wong et al. (2009) and total BDNF mRNA in layers III and V reported by Webster et al. (2002). Mature BDNF (mBDNF) protein levels reported by Wong et al. (2009). Abbreviations: dorsolateral prefrontal cortex, DLPFC.