Prion protein (PrP) is a
glycoprotein expressed on the surface of neurons and glial cells. Its pathological
isoform (
PrP(res)) is
protease resistant, and involved in the pathogenesis of a number of transmissible
encephalopathies (TSEs). One common feature of
neurodegenerative diseases, including TSEs, is oxidative stress, which may be responsible not only for the dysfunction or death of neuronal cells, but also cognitive deficits.
Clioquinol (5-chloro-7-iodo-8-quinolinol) chelates
zinc and
copper, which are involved in the deposition of
amyloid plaques and acts as an
antioxidant; increased lipid peroxidation has also been demonstrated in the early phases of PrP propagation. The aim of this study was to investigate the effects of
clioquinol on the changes in motor and cognitive behaviours induced by
scrapie infection, as well as its effects on oxidative stress and the
neurotransmitters known to be involved in motor and cognitive functions. The results show that
clioquinol counteracts the massive
memory deficit induced by
scrapie infection. This effect is not paralleled by neurochemical changes because the levels of all of the
biogenic amines and their metabolites were reduced despite
clioquinol treatment. The main biochemical change induced by
clioquinol was a marked reduction in lipid peroxidation at all time points. The
antioxidant effect of
clioquinol can reduce functional impairment and thus improve memory, but
clioquinol does not reduce PrP deposition or synapse loss, as indicated by the unchanged Western blot, histopathological and histochemical findings.