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.