RESUMO
UNLABELLED: Alzheimer's disease (AD) is expected to affect more than 22 million people worldwide by 2025, causing devastating suffering and enormous costs to families and society. AD is a multifactorial disease, with a complex pathological mosaic. In rodents, AD-like dementia can be induced by cerebral microinjection of Aß peptide, leading to amyloid deposits, amnesia and various features of neurodegeneration. Marapuama (Ptychopetalum olacoides) is regarded as a "brain tonic" in the Amazon region and shows a nootropic profile in rodents. AIM OF THE STUDY: Because a specific extract (POEE) of Marapuama was shown to possess promnesic and anti-amnesic properties, the aim of this study was to verify if POEE is also effective against Aß(1-42)-induced cognitive deficit in mice. Additionally, Aß deposits (Congo red), GFAP immunoreactivity (immunohistochemistry), and neurodegenerative changes in the hippocampal pyramidal layer (Nissl) were examined as measures of Aß(1-42)-induced neurodegeneration. MATERIALS AND METHODS: CF1 mice were subjected to the experimental Alzheimer model with the Aß(1-42) i.c.v. administration. The effects of POEE 800 mg/kg were evaluated over 14 consecutive days of treatment. RESULTS: The data show that 14 days of oral treatment with POEE (800 mg/kg) was effective in preventing Aß-induced cognitive impairment, without altering the levels of BDNF and with parallel reductions in Aß deposits and astrogliosis. CA1 hippocampus loss induced by Aß(1-42) was also diminished in POEE-treated mice. CONCLUSION: This study offers evidence of functional and neuroprotective effects of two weeks treatment with a Ptychopetalum olacoides extract against Aß peptide-induced neurotoxicity in mice. Given the multifactorial nature of neurodegeneration, the considerable potential for an AChE inhibitor displaying associated neuroprotective properties such as here reported warrants further clinic evaluation.
Assuntos
Transtornos Cognitivos/tratamento farmacológico , Degeneração Neural/tratamento farmacológico , Nootrópicos/farmacologia , Olacaceae/química , Fitoterapia , Extratos Vegetais/farmacologia , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Demência/tratamento farmacológico , Modelos Animais de Doenças , Progressão da Doença , Masculino , Camundongos , Neuroglia/patologia , Nootrópicos/uso terapêutico , Fragmentos de Peptídeos/farmacologia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/químicaRESUMO
The goal of acetylcholinesterase inhibitors (AChEIs) used to treat Alzheimer's patients is an improvement in cholinergic transmission. While currently available AChEIs have limited success, a huge impediment to the development of newer ones is access to the relevant brain areas. Promnesic, anti-amnesic and AChEI properties were identified in a standardized ethanol extract from Ptychopetalum olacoides (POEE), a medicinal plant favored by the elderly in Amazon communities. The purpose of this study was to provide conclusive evidence that orally given POEE induces AChE inhibition in brain areas relevant to cognition. Histochemistry experiments confirmed that the anticholinesterase compound(s) present in POEE are orally bioavailable, inducing meaningful AChE inhibition in the hippocampus CA1 (â¼33%) and CA3 (â¼20%), and striatum (â¼17%). Ellman's colorimetric analysis revealed that G1 and G4 AChE isoforms activities were markedly inhibited (66 and 72%, respectively) in hippocampus and frontal cortex (50 and 63%, respectively), while G4 appeared to be selectively inhibited (72%) in the striatum. Western blotting showed that POEE did not induce significant changes in the AChE immunocontent suggesting that its synthesis is not extensively modified. This study provides definitive proof of meaningful anticholinesterase activity compatible with the observed promnesic and anti-amnesic effects of POEE in mice, reaffirming the potential of this extract for treating neurodegenerative conditions where a hypofunctioning cholinergic neurotransmission is prominent. Adequate assessment of the safety and efficacy of this extract and/or its isolated active compound(s) are warranted.
Assuntos
Acetilcolinesterase/metabolismo , Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Nootrópicos/farmacologia , Olacaceae , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Cognição/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Doenças Neurodegenerativas/tratamento farmacológico , Raízes de Plantas , Isoformas de ProteínasRESUMO
The biological basis of the clinical efficacy of lithium in the treatment of mental illness has been extensively studied in neurones, but little is known about the effects of the drug on glia. Recently we showed that treatment of rats with clinically relevant doses of lithium chloride results in a 35% increase in the immunocontent of the astrocyte marker GFAP in the hippocampus. Here we studied the cytology of this phenomenon. Rats were treated for 4 weeks with a lithium diet which resulted in serum Li+ concentrations of 0.6-1.2 mmol/l. GFAP immunocytochemistry of the hippocampus revealed a mild gliosis in the CA1 area and the dentate gyrus which was associated with a change in the orientation of astrocytic processes. In control animals astrocyte processes were mainly orientated perpendicular to the stratum pyramidale, whereas in treated animals the cells were predominantly stellar in appearance.