Author/Editor     Milivojevič, Nataša
Title     Učinki N-tert-butil-alfa-fenil-nitrona na modelu kognitivne disfunkcije pri podgani
Type     monografija
Place     Ljubljana
Publisher     Medicinska fakulteta
Publication year     2001
Volume     str. 72
Language     slo
Abstract     It has been shown, that chronic treatment with free radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN) improves cognitive performance of aged rats. This finding was attributed to neuroprotective effects of PBN due to its free radical scavenging activity. Recently it has been found that PBN also exhibits anticholinesterase activity. In the model of diisopropylphosphorofluoridate-induced seizures, PBN partially protected AChE from critical irreversible phosphorylation (Milatović et al., 2000). Anticholinesterase activity of PBN was disclosed by in vitro studies where PBN inhibited rat brain AChE as mixed competitive/noncompetitive inhibitor with Ki and Ki' of 0.693 and 3.874 mM, respectively. It is known that reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. This raised the question whether the beneficial effects of PBN on cognitive performance could be explained by its anticholinesterase activity. In the present study I therefore compared the effects of PBN to the effects of reversible anticholinesterases physostigmine and tacrine on the impairment of spatial learning and memory induced by muscarinic antagonist scopolamine in the Morris water maze paradigm and on scopolamine induced locomotor hyperactivity in the open field behavioral experiment. In addition, using gene expression analysis by in situ hybridization method I examined whether PBN can antagonize the augmenting effects of scopolamine on the induction of immediate early gene (IEG; c jun) expression by SKF-82958. (Abstract truncated at 2000 characters)
Descriptors     COGNITION DISORDERS
FREE RADICAL SCAVENGERS
ACETYLCHOLINESTERASE
SCOPOLAMINE
PHYSOSTIGMINE
RATS, WISTAR
IN SITU HYBRIDIZATION
GENES, JUN
BEHAVIOR, ANIMAL
MEMORY
GENE EXPRESSION
TACRINE
RNA, MESSENGER
CORPUS STRIATUM