Aminoguanidine treatment ameliorates inflammatory responses and memory impairment induced by amyloid-beta 25-35 injection in rats.
Alzheimer disease (AD) is a neurodegenerative disorder caused by accumulation of the amyloid-beta peptide (Aβ) in neuritic plaques. Its neurotoxic mechanisms are associated with inflammatory responses and nitrosative stress generation that promote expression of inducible nitric oxide synthase (iNOS) and increased nitric oxide causing neuronal death and memory impairment. Studies suggest that treatment with anti-inflammatory and anti-oxidant agents decreases the risk of developing AD. Aminoguanidine (AG) is an iNOS inhibitor with anti-inflammatory and anti-oxidant effects. In this study, we evaluated the effects of systemic administration of AG (100 mg/kg/day for 4 days) on spatial memory and inflammatory responses induced by an injection of Aβ(25-35) [100 μM] into the temporal cortex (TCx) of rats. A significant improvement of spatial memory was evident in the Aβ(25-35)-treated group at day 30 post-injection subjected to AG treatment; this effect was correlated with decreases in reactive gliosis, IL-1β, TNF-α, and nitrite levels, as well as a reduction in neurodegeneration in the TCx and hippocampus (Hp). These results suggest that AG treatment inhibited glia activation and cytokine release, which may help to counteract neurodegenerative events induced by the toxicity of Aβ.
Facultad de Ciencias Químicas, BUAP, Puebla, PL, Mexico; Laboratorio Experimental de Enfermedades Neurodegenerativas, INNN-MVS, Mexico, DF, Mexico; Departamento de Bioquímica, Facultad de Medicina, UNAM, Mexico, DF, Mexico.
Alfonso
A
Díaz
Laboratorio Experimental de Enfermedades Neurodegenerativas, INNN-MVS, Mexico, DF, Mexico.
Karla
K
Rojas
Laboratorio de Bioquímica, INER-ICV, Mexico, DF, Mexico.
Blanca
B
Espinosa
Departamento de Bioquímica, Facultad de Medicina, UNAM, Mexico, DF, Mexico.
Raúl
R
Chávez
Departamento de Bioquímica, Facultad de Medicina, UNAM, Mexico, DF, Mexico.
Edgar
E
Zenteno
Facultad de Ciencias Químicas, BUAP, Puebla, PL, Mexico.
Daniel
D
Limón
Departamento de Bioquímica, Facultad de Medicina, UNAM, Mexico, DF, Mexico. Electronic address: Jorge.Guevara@comunidad.unam.mx.
Jorge
J
Guevara
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects; D013702:Temporal Lobe / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D006146:Guanidines; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D052247:Nitric Oxide Synthase Type II; C004479:pimagedine
Alzheimer disease; IL-1β; Neuroprotection; Nitric oxide; Spatial memory; iNOS