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Psychopharmacology (Berl) ; 236(2): 641-655, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30377748

RESUMO

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. The present study investigated the effects of 50 and 100 mg/kg berberine (BRB) on recognition memory, oxidative stress, and purinergic neurotransmission, in a model of sporadic dementia of the Alzheimer's type induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats. Rats were submitted to ICV-STZ 3 mg/kg or saline, and 3 days later, were started on a treatment of BRB or saline for 21 days. The results demonstrated that BRB was effective in protecting against memory impairment, increased reactive oxygen species, and the subsequent increase in protein and lipid oxidation in the cerebral cortex and hippocampus, as well as δ-aminolevulinate dehydratase inhibition in the cerebral cortex. Moreover, the decrease in total thiols, and the reduced glutathione and glutathione S-transferase activity in the cerebral cortex and hippocampus of ICV-STZ rats, was prevented by BRB treatment. Besides an antioxidant effect, BRB treatment was capable of preventing decreases in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (EC-5'-Nt), and adenosine deaminase (ADA) activities in synaptosomes of the cerebral cortex and hippocampus. Thus, our data suggest that BRB exerts a neuroprotective effect on recognition memory, as well as on oxidative stress and oxidative stress-related damage, such as dysfunction of the purinergic system. This suggests that BRB may act as a promising multipotent agent for the treatment of AD.


Assuntos
Berberina/farmacologia , Encéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Reconhecimento Psicológico/efeitos dos fármacos , 5'-Nucleotidase/efeitos dos fármacos , 5'-Nucleotidase/metabolismo , Adenosina Desaminase/efeitos dos fármacos , Adenosina Desaminase/metabolismo , Doença de Alzheimer/psicologia , Animais , Antibióticos Antineoplásicos/toxicidade , Antioxidantes , Encéfalo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Glutationa , Glutationa Transferase/efeitos dos fármacos , Glutationa Transferase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Injeções Intraventriculares , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Oxirredução/efeitos dos fármacos , Pirofosfatases/efeitos dos fármacos , Pirofosfatases/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina/toxicidade , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/enzimologia
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