Cellular prion protein is present in dopaminergic neurons and modulates the dopaminergic system.
Cellular prion protein (PrP(C) ) is widely expressed in the brain. Although the precise role of PrP(C) remains uncertain, it has been proposed to be a pivotal modulator of neuroplasticity events by regulating the glutamatergic and serotonergic systems. Here we report the existence of neurochemical and functional interactions between PrP(C) and the dopaminergic system. PrP(C) was found to co-localize with dopaminergic neurons and in dopaminergic synapses in the striatum. Furthermore, the genetic deletion of PrP(C) down-regulated dopamine D1 receptors and DARPP-32 density in the striatum and decreased dopamine levels in the prefrontal cortex of mice. This indicates that PrP(C) affects the homeostasis of the dopaminergic system by interfering differently in different brain areas with dopamine synthesis, content, receptor density and signaling pathways. This interaction between PrP(C) and the dopaminergic system prompts the hypotheses that the dopaminergic system may be implicated in some pathological features of prion-related diseases and, conversely, that PrP(C) may play a role in dopamine-associated brain disorders.
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, Brazil; Center for Neuroscience and Cell Biology, Faculty of Medicine, Rua Larga University of Coimbra, 3004-504 Coimbra, Portugal.
Daniel
D
Rial
Fabrício A
FA
Pamplona
Eduardo L G
EL
Moreira
Karin M
KM
Moreira
Débora
D
Hipolide
Diana I
DI
Rodrigues
Patrícia A
PA
Dombrowski
Claudio
C
Da Cunha
Paula
P
Agostinho
Reinaldo N
RN
Takahashi
Roger
R
Walz
Rodrigo A
RA
Cunha
Rui D
RD
Prediger
D000818:Animals; D004298:Dopamine / Q000096:biosynthesis*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000032:analysis; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D017072:Neostriatum / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D018621:PrPC Proteins; D017447:Receptors, Dopamine D1; C098593:dopamine D1A receptor; D004298:Dopamine
behavior; cellular prion protein; dopamine; dopamine receptor; striatum