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. 2008 Oct 8;19(15):1473-7.
doi: 10.1097/WNR.0b013e32830f1e90.

Hypothalamic-pituitary-adrenal axis disregulation in PrPC-null mice

Manuel Sanchez-Alavez  1 , José R Criado, Izabella Klein, Gianluca Moroncini, Bruno Conti
Affiliations

Hypothalamic-pituitary-adrenal axis disregulation in PrPC-null mice

Manuel Sanchez-Alavez et al. Neuroreport. .

Abstract

As manifestations of prion diseases include disturbances of hypothalamic and pituitary functions, we tested the hypothesis that the cellular prion protein (PrPC) has a role as modulator of the hypothalamic-pituitary-adrenal axis. The level of corticosterone and adrenocorticotropic hormone were compared in PrPC null (PrP 0/0) and wild-type (PrP+/+) mice. PrP 0/0 showed hypercorticism during the dark part of day. After acute stress, corticosterone and adrenocorticotropic hormone increased similarly in PrP+/+ and PrP 0/0 mice. Adrenocorticotropic hormone, however, remained elevated in PrP+/+ 0/0 mice at corticosterone levels that are inhibitory in PrP mice. Pretreatment with corticosterone or dexamethasone inhibited stress-induced elevation of adrenocorticotropic hormone in PrP+/+ but not in PrP 0/0 mice. Thus, PrPC may play a role in the negative feedback regulation of axis.

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Figures

Figure 1
Figure 1
Circadian profile of corticosterone level in mPrP+/+ and mPrP0/0 mice. Plasma corticosterone levels were determined at three hrs intervals during 24 hrs starting at 6:00 AM (n= 5 per point; *p< 0.05)
Figure 2
Figure 2
Adrenocorticotropic hormone (ACTH) and corticosterone (Cort) levels during acute restraint stress. mPrP+/+ and mPrP0/0 mice subject to restraint stress for 15, 30, 60 or 120 minutes (n=5, *p< 0.05)
Figure 3
Figure 3
Adrenocorticotropic hormone (ACTH) and corticosterone (Cort) levels following corticosterone pretreatment. Mice received no stress (NS) or 30 minutes of restraint stress (30′) 1 hr after pretreatment with saline (Sal) or corticosterone (Cort) (n=5; *p<0.05; **= not significant)
Figure 4
Figure 4
Adrenocorticotropic hormone (ACTH) and corticosterone (Cort) levels following dexamethasone (Dex) pretreatment. Mice received no stress (NS) or 15 minutes of restraint stress (15′) 1 hr after pretreatment with saline (Sal) or Dex (n=5; *p<0.05; **= not significant)
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References

    1. Weissmann C, Enari M, Klohn PC, Rossi D, Flechsig E. Molecular biology of prions. Acta Neurobiol Exp. 2002;62:153–166. - PubMed
    1. Jacobson L, Sapolsky R. The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocrine Reviews. 1991;12(2):118–134. - PubMed
    1. Parry HB. Studies in scrapie. Veterinary Record. 1957;69:1318–1324.
    1. Parry HB. Scrapie: a transmissible and hereditary disease of sheep. Heredity. 1962;17:75–105. - PubMed
    1. Beck E, Daniel PM, Parry HB. Degeneration of the cerebellar and hypothalamoneurohypophysial systems in sheep with scrapie; and its relationship to human system degenerations. Brain Pathol. 1964;87:153–176. - PubMed

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