Changes in sympathetic activity in prion neuroinvasion

Prion diseases are neurodegenerative diseases affecting humans and animals in which the infectious agent or prion is PrPres, a protease-resistant conformer of the cell protein PrP. The natural transmission route of prion diseases is peripheral infection, with the lymphoreticular system (LRS) and peripheral nerves being involved in animal models of scrapie neuroinvasion and human prion diseases. To study the effects of PrP neuroinvasion on sympathetic nerve function, we measured plasma catecholamine levels, blood pressure, heart rate, and PrP tissue levels in intraperitoneally or intracerebrally infected mice. The results indicate a specific alteration in sympathetic nerve function because the levels of noradrenaline (but not adrenaline) were increased in the animals infected peripherally (but not in those infected intracerebrally) and correlated with increased blood pressure.These findings confirm that prion neuroinvasion uses the sympathetic nervous system to spread from the periphery to the central nervous system after invading the LRS.