RESUMO
Nicotine is the principal psychoactive ingredient in cigarette smoke, and has been associated with health problems in humans. However, the pure form of nicotine may prove to be a valuable pharmaceutical agent for the treatment of AD. However, the beneficial effects of nicotine remain a matter of much controversy. In order to clarify this issue, 12-month-old transgenic mice, expressing neuron-specific enolase (NSE)-controlled APPsw, were treated with low, middle, and high doses of nicotine for 6 months. Herein, we have concluded that the nicotine-treated groups evidenced improvements in behavior and increases in the nicotine acetylcholine receptor, nAchRalpha7. These findings provide experimental evidence that nicotine effects an improvement in impaired memory, and that this improvement is associated with an increase in nAchRalpha7. Thus, nicotine may prove a good preventative or therapeutic modality for AD patients.
Assuntos
Comportamento Animal/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Receptores Nicotínicos/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Feminino , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Estrutura Molecular , Nicotina/química , Nicotina/uso terapêutico , Agonistas Nicotínicos/química , Agonistas Nicotínicos/uso terapêutico , Fosfopiruvato Hidratase/genética , Receptor Nicotínico de Acetilcolina alfa7RESUMO
Humanized transgenic mice coexpressing tetracycline-controlled transactivator (tTA) and human cytochrome P450 1B1 (CYP1B1) (hCYP1B1) have been created by this group. The aims of this study was to determine if 7,12-dimethylbenz[a]anthracene (DMBA) functions as testosterone or doxycycline in its ability to induce or reduce expression of hCYP1B1 or endogenous mouse CYP1B1 (mCYP1B1). This was tested in the livers by treating castrated transgenic males and hCYP1B1/luciferase-transfected cells with DMBA. Herein, DMBA-treated group exhibited (i) gradual reduction of hCYP1B1 expression at the transcript, protein, and activity levels but gradually induced its transcript level during DMBA release; (ii) gradual reduction of hCYP1B1 at the transcript and protein levels, as in the case of doxycycline or testosterone; (iii) gradual induction of mCYP1B1 expression at the transcript and protein levels but gradually reduced its transcript level during DMBA release. In parallel, DMBA-treated transfected cells exhibited gradual increase in luciferase activity in a time-and dose-dependent manner. Thus, castrated transgenic males or in vitro system could be useful as models for the detection of polycyclic aromatic hydrocarbons (PAHs) or environmental toxicants by measuring either hCYP1B1 or mCYP1B1 expressions.