Unaltered susceptibility to scrapie in serotonin transporter deficient mice.
The serotonergic system has been hypothesized to play an important role in prion diseases. Specifically, hyperactivity of the serotonergic system in prion diseases is suggested by an increase in the turnover rate of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in human and experimental prion diseases. The 5-HT transporter (5-HTT) determines the duration of serotonergic neurotransmission by way of reuptake of 5-HT from the extracellular space. 5-HTT availability is reduced in brains of patients with the human prion disease familial fatal insomnia. To further clarify a possible role of the 5-HTT in prion diseases we investigated whether mice lacking the 5-HTT display an altered susceptibility to experimental scrapie infection. Surprisingly, 5-HTT knockout mice developed mouse scrapie in a time course similar to wildtype control mice with accumulation of the pathological prion protein, PrP(Sc) and with typical pathological hallmarks of the disease. These findings argue against a major role of the 5-HTT in the pathogenesis of prion diseases in mice.
Mössner
Rainald
R
Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. rainald.moessner@mail.uni-wuerzburg.de
Yun
Seong-Wook
SW
Lesch
Klaus-Peter
KP
Gerlach
Manfred
M
Klein
Michael A
MA
Riederer
Peter
P
D000818:Animals; D015153:Blotting, Western; D004198:Disease Susceptibility; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018620:PrPSc Proteins / Q000378:metabolism; D012608:Scrapie / Q000235:genetics / Q000503:physiopathology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*
D018620:PrPSc Proteins; D050486:Serotonin Plasma Membrane Transport Proteins