Citation

Beckman D, Santos LE, Americo TA, Ledo JH, de Mello FG, Linden R. J. Biol. Chem. 2015; 290(33): 20488-20498.

Affiliation

Instituto de Biofisica da UFRJ, Brazil; rlinden@biof.ufrj.br.

Copyright

(Copyright © 2015, American Society for Biochemistry and Molecular Biology)

DOI

10.1074/jbc.M115.666156

PMID

26152722

Abstract

We sought to examine interactions of the prion protein (PrP(C)) with monoaminergic systems due to: the role of PrP(C) in both Prion and Alzheimer's Diseases, which include clinical depression among their symptoms; the implication of monoamines in depression; and the hypothesis that PrPC serves as a scaffold for signaling systems. To that effect we compared both behavior and monoaminergic markers in wildtype (WT) and PrP(C)-null (PrP(-/-)) mice. PrP(-/-) mice performed poorly when compared with WT in forced swimming, tail suspension, and novelty suppressed feeding tests, typical of depressive-like behavior, but not in the control open field nor rotarod motor tests; Cyclic AMP responses to stimulation of D1 receptors by dopamine was selectively impaired in PrP(-/-) mice, and responses to serotonin, but not to norepinephrine, also differed between genotypes. Contents of dopamine, tyrosine hydroxylase and the 5-HT5A serotonin receptor were increased in the cerebral cortex of PrP(-/-), as compared to WT mice. Microscopical colocalization, as well as binding in overlay assays were found of PrP(C) with both the 5HT5A and D1, but not D4 receptors. The data are consistent with the scaffolding of monoaminergic signaling modules by PrP(C), and may help understand the pathogenesis of clinical depression and neurodegenerative disorders.

Language: en