RESUMO
The function of synaptic transmission and presynaptic vesicular cycle in the neuromuscular synapses of the diaphragm was studied in transgenic APP/PS1 mice (Alzheimer's disease model). The decrease in the quantal content of end-plate potential, intense depression of the amplitude of terminal plate potentials under conditions of lasting high frequency stimulation (50 Hz), a drastic prolongation of the synaptic vesicle recycling time in APP/PS1 mice in comparison with wild type mice were detected. Manifest dysfunction of the neuromuscular synapses, caused by disordered neurosecretion and recycling of the synaptic vesicles in the presynaptic nerve endings, was detected in the Alzheimer's disease model on transgenic APP/PS1 mice. The study supplemented the notions on the pathogenesis of Alzheimer's disease as a systemic disease, while the detected phenomena could just partially explain the development of motor disorders in this disease.
Assuntos
Doença de Alzheimer/fisiopatologia , Placa Motora/fisiopatologia , Terminações Pré-Sinápticas/patologia , Transmissão Sináptica , Vesículas Sinápticas/patologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Modelos Animais de Doenças , Estimulação Elétrica , Endocitose , Exocitose , Expressão Gênica , Humanos , Camundongos , Camundongos Transgênicos , Placa Motora/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Terminações Pré-Sinápticas/metabolismo , Vesículas Sinápticas/metabolismoRESUMO
The article presents results of research evaluating psychoemotional condition of patients with the malignant tumour diagnosis both single and having their family's support. The research results showed the difference in mood, health and general activity, situational anxiety and aggression. The received results can be considered when preparing elderly patients for operation and during the post operational period for the purpose of psychological maintenance and minimization of complications.
Assuntos
Neoplasias/psicologia , Afeto , Idoso , Ansiedade , Humanos , Neoplasias/diagnóstico , Pesquisa , Apoio SocialRESUMO
Age-related development of behavioral disorders in transgenic mice with modeled Alzheimer's disease carrying V6S3-Tg(APP695)85Dbo Tg(PSENI)85Dbo) genotype was assessed at the age of 7.5, 10 and 20 months in the following tests: open-field, plus maze, T-maze, conditioned passive avoidance response, rotarod, conflict situation with water deprivation, behavioral despair, and arecoline tremor. The main behavioral disorder in transgenic mice at all observation terms was memory impairment in conditioning with positive (but not negative) reinforcement. At the age of 7.5 and 10 months, transgenic mice also showed signs of nonspecific excitement and anxiety, depression-like state, and symptoms of cholinergic deficit. Our results suggest that appropriate age for behavioral tests in studies of effects of potential anti-Alzheimer drugs in transgenic V6S3-Tg(APP695)85Dbo Tg(PSENI)85Dbo) mice is 7.5-10 months.
Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/tratamento farmacológico , Precursor de Proteína beta-Amiloide/genética , Animais , Ansiedade/tratamento farmacológico , Ansiedade/patologia , Ansiedade/fisiopatologia , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Transtornos da Memória/fisiopatologia , Camundongos , Camundongos Transgênicos , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Excess production and accumulation of beta-amyloid peptide (betaAP) are central for pathogenesis of Alzheimer's disease. Numerous studies showed that betaAP possessed wide range of toxic effects on neurons, however the mechanism of betaAP influence on another types of excitable cells, for example, skeletal muscle fibres, is unknown. In electrophysiological experiments on the mouse diaphragm, we found for the first time that betaAP (25-35 fragment, 10-6 M) disturbs the processes of the resting membrane potential generation in muscle fibres, leading to depolarization by two mechanisms: 1) inhibition of Na+,K(+)-ATPase, which leads to loss of impact of this pump to the resting membrane potential; 2) increase of membrane cationic permeability due to formation of "amyloid" channels blocked with Zn2+ ions. Our results significantly broaden current understanding of mechanisms of motor disturbances and skeletal muscle pathology in Alzheimer's disease, inclusion body myositis and other betaAP-related disorders.
