Neurobiological consequences of acute footshock stress: effects on tyrosine hydroxylase phosphorylation and activation in the rat brain and adrenal medulla

Authors

  • Lin Kooi Ong,

    1. School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, The University of Newcastle, NSW, Australia
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  • Liying Guan,

    1. School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, The University of Newcastle, NSW, Australia
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  • Hanafi Damanhuri,

    1. The Australian School of Advance Medicine, Macquarie University, NSW, Australia
    2. Biochemistry Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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  • Ann K. Goodchild,

    1. The Australian School of Advance Medicine, Macquarie University, NSW, Australia
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  • Larisa Bobrovskaya,

    1. School of Pharmacy and Medical Sciences, University of South Australia, SA, Australia
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  • Phillip W. Dickson,

    1. School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, The University of Newcastle, NSW, Australia
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  • Peter R. Dunkley

    Corresponding author
    1. School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, The University of Newcastle, NSW, Australia
    • Address correspondence and reprint request to Peter R. Dunkley, School of Biomedical Science and Pharmacy and the Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, Australia. E-mail: peter.dunkley@newcastle.edu.au

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Abstract

Stress activates selected neuronal systems in the brain and this leads to activation of a range of effector systems. Our aim was to investigate some of the relationships between these systems under basal conditions and over a 40-min period in response to footshock stress. Specifically, we investigated catecholaminergic neurons in the locus coeruleus (LC), ventral tegmental area and medial prefrontal cortex (mPFC) in the brain, by measuring tyrosine hydroxylase (TH) protein, TH phosphorylation and TH activation. We also measured the effector responses by measuring plasma adrenocorticotrophic hormone, corticosterone, glucose and body temperature as well as activation of adrenal medulla protein kinases, TH protein, TH phosphorylation and TH activation. The LC, ventral tegmental area and adrenal medulla all had higher basal levels of Ser19 phosphorylation and lower basal levels of Ser31 phosphorylation than the mPFC, presumably because of their cell body versus nerve terminal location, while the adrenal medulla had the highest basal levels of Ser40 phosphorylation. Ser31 phosphorylation was increased in the LC at 20 and 40 min and in the mPFC at 40 min; TH activity was increased at 40 min in both tissues. There were significant increases in body temperature between 10 and 40 min, as well as increases in plasma adrenocorticotropic hormone at 20 min and corticosterone and glucose at 20 and 40 min. The adrenal medulla extracellular signal-regulated kinase 2 was increased between 10 and 40 min and Ser31 phosphorylation was increased at 20 min and 40 min. Protein kinase A and Ser40 phosphorylation were increased only at 40 min. TH activity was increased between 20 and 40 min. TH protein and Ser19 phosphorylation levels were not altered in any of the brain regions or adrenal medulla over the first 40 min. These findings indicate that acute footshock stress leads to activation of TH in the LC, pre-synaptic terminals in the mPFC and adrenal medullary chromaffin cells, as well as changes in activity of the hypothalamic-pituitary-adrenal axis.

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We measured the basal levels of tyrosine hydroxylase phosphorylation and determined the effects of footshock stress over a 40 minute period. Footshock leads to changes in the activity of neurons in the locus coeruleus (LC) and presynaptic terminals in the medial prefrontal cortex (mPFC), as well as changes in activity of the hypothalamic-pituitary-adrenal (HPA) axis and adrenal medullary (AM) chromaffin cells.

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