Lacidipine Prevents Scopolamine-Induced Memory Impairment by Reducing Brain Oxido-nitrosative Stress in Mice.
Neurotox Res
; 39(4): 1087-1102, 2021 Aug.
Article
em En
| MEDLINE
| ID: mdl-33721210
ABSTRACT
Cholinergic deficits and oxido-nitrosative stress are consistently associated with Alzheimer's disease (AD). Previous findings indicate that acetylcholine subdues Ca2+ current in the brain. Cholinergic antagonists (e.g., scopolamine) can instigate Ca2+-induced redox imbalance, inflammation, and cell-death pathways leading to AD-type memory impairment. Earlier, several Ca2+-channel blockers (CCB, e.g., dihydropyridine type) or cholinergic enhancers showed promising results in animal models of AD. In the present research, pretreatment effects of lacidipine (L-type CCB) on learning and memory functions were investigated using the scopolamine mouse model of AD. Swiss albino mice (20-25 g) were administered lacidipine (1 and 3 mg/kg) for 14 days. Scopolamine, an anti-muscarinic drug, was given (1 mg/kg) from days 8 to 14. The mice were subjected to elevated plus maze (EPM) and passive-avoidance (PA) paradigms. Bay-K8644 (a Ca2+-channel agonist) was administered before behavioral studies on days 13 and 14. Biochemical parameters of oxidative stress and acetylcholinesterase (AChE) activity were quantified using the whole brain. Behavioral studies showed an increase in transfer latency (TL) in the EPM test and a decrease in step-through latency (STL) in the PA test in scopolamine-administered mice. Scopolamine enhanced the AChE activity and oxidative stress in the brain of mice which resulted in memory impairment. Lacidipine prevented the amnesia against scopolamine and reduced the oxidative stress and AChE activity in the brain of mice. Bay-K8644 attenuated the lacidipine-induced improvement in memory and redox balance in scopolamine-administered mice. Lacidipine can prevent the oxidative stress and improve the cholinergic function in the brain. These properties of lacidipine can mitigate the pathogenesis of AD-type dementia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Escopolamina
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Encéfalo
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Di-Hidropiridinas
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Estresse Oxidativo
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Estresse Nitrosativo
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Transtornos da Memória
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurotox Res
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Índia