Effects of clioquinol on memory impairment and the neurochemical modifications induced by scrapie infection in golden hamsters.
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.
Bareggi
Silvio R
SR
Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milano, Italy. silvio.bareggi@unimi.it
Braida
Daniela
D
Pollera
Claudia
C
Bondiolotti
Gianpietro
G
Formentin
Elena
E
Puricelli
Maria
M
Poli
Giorgio
G
Ponti
Wilma
W
Sala
Mariaelvina
M
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002614:Chelating Agents / Q000627:therapeutic use; D007464:Clioquinol / Q000627:therapeutic use*; D006224:Cricetinae; D005260:Female; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology*; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects; D011897:Random Allocation; D012608:Scrapie / Q000150:complications* / Q000188:drug therapy*; D013997:Time Factors
D000975:Antioxidants; D001679:Biogenic Amines; D002614:Chelating Agents; D007464:Clioquinol