title: Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice.
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 diseases, which include clinical depression among their symptoms, the implication of monoamines in depression, and the hypothesis that PrP(C) serves as a scaffold for signaling systems. To that effect we compared both behavior and monoaminergic markers in wild type (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 with WT mice. Microscopic 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.
authors.affiliation: From the Instituto de Biofísica and.
authors.forename: Danielle
authors.initials: D
authors.lastname: Beckman
authors.affiliation: From the Instituto de Biofísica and.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Santos
authors.affiliation: From the Instituto de Biofísica and.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Americo
authors.affiliation: Instituto de Bioquímica Médica da UFRJ, Rio de Janeiro 21941-902, Brasil.
authors.forename: Jose H
authors.initials: JH
authors.lastname: Ledo
authors.affiliation: From the Instituto de Biofísica and.
authors.forename: Fernando G
authors.initials: FG
authors.lastname: de Mello
authors.affiliation: From the Instituto de Biofísica and rlinden@biof.ufrj.br.
authors.forename: Rafael
authors.initials: R
authors.lastname: Linden
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015306:Biogenic Monoamines / Q000502:physiology*; D003863:Depression / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018621:PrPC Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D015306:Biogenic Monoamines; D018621:PrPC Proteins
keywords: Alzheimer disease; cerebral cortex; depression; monoaminergic neurotransmission; neurodegeneration; prion; prion disease