Spermine improves recognition memory deficit in a rodent model of Huntington's disease.
Huntington's disease (HD) is a progressive neurodegenerative disorder associated with motor and cognitive impairment. Intrastriatal administration of quinolinic acid (QA) causes neurodegeneration, glial proliferation and cognitive impairment in animals, which are similar to these seen in human HD. Since polyamines improve memory in cognitive tasks, we now tested if the post-training intrastriatal administration of spermine, an agonist of the polyamine site at the NMDA receptor, reverses the deficits in the object recognition task induced by QA. Bilateral striatal injections of QA (180 or 360 nmol/site) caused object recognition impairment, neuronal death and reactive astrogliosis. A single injection of spermine (0.1 and 1 nmol/site), 5 days after QA injection, reversed QA-induced impairment of object recognition task. Spermine (0.1 nmol/site) also inhibited QA-induced reactive astrogliosis measured by a semi-quantitative determination of GFAP immunolabelling, but did not alter neuronal death, measured by a semi-quantitative determination of fluoro-Jade C staining. These results suggest that polyamine binding sites may be considered a novel therapeutic target to prevent reactive astrogliosis and mnemonic deficits in HD.
Velloso
Nádia A
NA
Department of Chemistry, Center of Exact and Natural Sciences, Universidade Federal de Santa Maria, Santa Maria 97105-900, RS, Brazil.
Dalmolin
Gerusa D
GD
Gomes
Guilherme M
GM
Rubin
Maribel A
MA
Canas
Paula M
PM
Cunha
Rodrigo A
RA
Mello
Carlos F
CF
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use; D006816:Huntington Disease / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy*; D017072:Neostriatum / Q000187:drug effects; D018697:Nootropic Agents / Q000627:therapeutic use*; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D021641:Recognition, Psychology / Q000187:drug effects*; D013096:Spermine / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
D018690:Excitatory Amino Acid Agonists; D018697:Nootropic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D017378:Quinolinic Acid