Spermine improves recognition memory deficit in a rodent model of Huntington’s disease

• Published in: Neurobiology of learning and memory Vol. 92; no. 4; pp. 574 - 580
• Main Authors: Velloso, Nádia A., Dalmolin, Gerusa D., Gomes, Guilherme M., Rubin, Maribel A., Canas, Paula M., Cunha, Rodrigo A., Mello, Carlos F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.11.2009; Elsevier; Elsevier BV
• Subjects: Adult and adolescent clinical studies; Analysis of Variance; Animals; Astrocytes; Behavioral psychophysiology; Biological and medical sciences; Cognitive ability; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists - therapeutic use; Fundamental and applied biological sciences. Psychology; Huntington Disease - chemically induced; Huntington Disease - complications; Huntington Disease - drug therapy; Huntingtons disease; Huntington’s disease; Male; Medical sciences; Memory; Memory Disorders - complications; Memory Disorders - drug therapy; Motor ability; Neostriatum - drug effects; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Nootropic Agents - therapeutic use; Object discrimination; Organic mental disorders. Neuropsychology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Quinolinic Acid; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate - agonists; Recognition (Psychology) - drug effects; Rodents; Spermine; Spermine - therapeutic use; Statistics, Nonparametric; Striatum; Striatum; Spermine; Astrocytes; Memory; Huntington’s disease; Quinolinic acid; Object discrimination; Animal model; Memory disorder; Recognition memory; Cognitive disorder; Neuroglia; Central nervous system; Encephalon; Degenerative disease; Nervous system diseases; Huntington disease; Basal ganglion; Corpus striatum; Astrocyte; Huntington's disease; Genetic disease; Cerebral disorder; Discrimination; Animal; Central nervous system disease; Extrapyramidal syndrome
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2009.07.006

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.