Memantine reduces oxidative damage and enhances long-term recognition memory in aged rats.
Many neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases (HD), are caused by different mechanisms but may share a common pathway to neuronal injury as a result of the overstimulation of glutamate receptors. It has been suggested that this pathway can be involved in generation of cognitive deficits associated with normal aging. Previous studies performed in our laboratory have demonstrated that aged rats presented recognition memory deficits. The aim of the present study was to evaluate the effect of memantine, a low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist, on age-induced recognition memory deficits. Additionally, parameters of oxidative damage in cerebral regions related to memory formation were evaluated. In order to do that, male Wistar rats (24 months old) received daily injections of saline solution or memantine (20 mg/kg i.p.) during 21 days. The animals were submitted to a novel object recognition task 1 week after the last injection. Memantine-treated rats showed normal recognition memory while the saline group showed long-term recognition memory deficits. The results show that memantine is able to reverse age-induced recognition memory deficits. We also demonstrated that memantine reduced the oxidative damage to proteins in cortex and hippocampus, two important brain regions involved in memory formation. Thus, the present findings suggest that, at least in part, age-induced cognitive deficits are related to oxidative damage promoted by NMDA receptor overactivation.
Pietá Dias
C
C
Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
Martins de Lima
M N
MN
Presti-Torres
J
J
Dornelles
A
A
Garcia
V A
VA
Siciliani Scalco
F
F
Rewsaat Guimarães
M
M
Constantino
L
L
Budni
P
P
Dal-Pizzol
Felipe
F
Schröder
N
N
D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D008559:Memantine