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Identification of chronic stress‐activated regions reveals a potential recruited circuit in rat brain

Flak, Jonathan N. ; Solomon, Matia B. ; Jankord, Ryan ; Krause, Eric G. ; Herman, James P.

European Journal of Neuroscience, August 2012, Vol.36(4), pp.2547-2555 [Periódico revisado por pares]

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  • Título:
    Identification of chronic stress‐activated regions reveals a potential recruited circuit in rat brain
  • Autor: Flak, Jonathan N. ; Solomon, Matia B. ; Jankord, Ryan ; Krause, Eric G. ; Herman, James P.
  • Assuntos: Δfosb ; Dorsomedial Hypothalamic Nucleus ; Medial Prefrontal Cortex ; Nucleus Of The Solitary Tract ; Posterior Hypothalamic Nucleus
  • É parte de: European Journal of Neuroscience, August 2012, Vol.36(4), pp.2547-2555
  • Descrição: Chronic stress induces presynaptic and postsynaptic modifications in the paraventricular nucleus of the hypothalamus that are consistent with enhanced excitatory hypothalamo‐pituitary‐adrenocortical (HPA) axis drive. The brain regions mediating these molecular modifications are not known. We hypothesized that chronic variable stress (CVS) tonically activates stress‐excitatory regions that interact with the paraventricular nucleus of the hypothalamus, culminating in stress facilitation. In order to identify chronically activated brain regions, ΔFosB, a documented marker of tonic neuronal activation, was assessed in known stress regulatory limbic and brainstem sites. Four experimental groups were included: CVS, repeated restraint (RR) (control for HPA habituation), animals weight‐matched (WM) to CVS animals (control for changes in circulating metabolic factors due to reduced weight gain), and non‐handled controls. CVS, (but not RR or WM) induced adrenal hypertrophy, indicating that sustained HPA axis drive only occurred in the CVS group. CVS (but not RR or WM) selectively increased the number of FosB/ΔFosB nuclei in the nucleus of the solitary tract, posterior hypothalamic nucleus, and both the infralimbic and prelimbic divisions of the medial prefrontal cortex, indicating an involvement of these regions in chronic drive of the HPA axis. Increases in FosB/ΔFosB‐immunoreactive cells were observed following both RR and CVS in the other regions (e.g. the dorsomedial hypothalamus), suggesting activation by both habituating and non‐habituating stress conditions. The data suggest that unpredictable stress uniquely activates interconnected cortical, hypothalamic, and brainstem nuclei, potentially revealing the existence of a recruited circuitry mediating chronic drive of brain stress effector systems. Chronic variable stress (CVS) causes specific enhancement of delta‐FosB expression in select central regulatory circuits, including the prefrontal cortex, posterior hypothalamic nucleus and nucleus of the solitary tract. Delta‐FosB changes are not observed in a habituating stress regimen (repeated restraint), implying that CVS‐related changes are driven by recruitment of these key cortical, hypothalamic and hindbrain circuits.

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