Blockade of adenosine A2A receptor counteracts neuropeptide-S-induced hyperlocomotion in mice.

Neuropeptide S (NPS) is the endogenous ligand of a G-protein-coupled receptor named as NPSR. Behavioral effects have been recently attributed to NPS, i.e. hyperlocomotion, anxiolysis, and wakefulness. However, little is known about the mechanisms by which NPS evokes such biological actions. The present study aimed to investigate the role played by the adenosine A(2A) and A(1) receptors in hyperlocomotion induced by NPS. Spontaneous locomotion was assessed in an activity cage for 30 min in mice acutely treated with caffeine (a nonselective adenosine receptor antagonist), ZM241385 (a selective A(2A) receptor antagonist), or CPT (a selective A(1) receptor antagonist) before NPS challenge (0.1 nmol, i.c.v.), which induce hyperlocomotion in mice. The pretreatment with caffeine (3 mg/kg, i.p.), in an inactive dose per se, prevented the increase in locomotion evoked by NPS. The co-administration of NPS (0.1 nmol, i.c.v.) and ZM241385 (0.1 pmol, i.c.v.) counteracted hyperlocomotion evoked by NPS. The co-administration of NPS and CPT (0.1 pmol, i.c.v.) slightly facilitated the increase in locomotion evoked by NPS alone. In summary, the pharmacological blockade of A(2A) receptors significantly attenuated the stimulatory effects of NPS. By contrast, the antagonism of A(1) receptors facilitated NPS-induced hyperlocomotion in mice, but we cannot rule out a merely additive effect of two stimulatory systems in the brain. Altogether, this is the first evidence of a putative role played by A(2A) and A(1) receptors in modulating hyperlocomotion induced by NPS.

Análise da fadiga central e seu impacto na qualidade de vida dos pacientes portadores de doenças neuromusculares / Analysis of central fatigue and its impact in the quality of life of patients with neuromuscular diseases

Entende-se por doenças neuromusculares aquelas afecções decorrentes do acometimento primário da unidade motora, sendo que, nas crianças, a maior parte dessas afecções é geneticamente determinada. As doenças neuromusculares levam ao comprometimento progressivo da função pulmonar e motora, levando a alterações significativas destas e acentuando o surgimento da fadiga muscular central. A qualidade de vida é considerada como um importante indicador de prognóstico e de evolução das doenças neuromusculares, a qual é utilizada como forma de avaliar o risco de adoecer, além de indicador válido e importante dos benefícios globais do tratamento do paciente. O estudo teve o propósito de avaliar a fadiga central e seu impacto na qualidade de vida dos pacientes com doenças neuromusculares. Foi realizada uma avaliação contendo itens como idade, tempo de diagnóstico, funcionalidade, espirometria, pressão inspiratória e expiratória máximas, escala de severidade de fadiga, desempenho muscular e questionário de qualidade de vida. Na avaliação da qualidade de vida, notou-se que os pacientes avaliados não apresentavam sintomas de fadiga, mas, sintomas de depressão associados com relatos de insatisfação nos itens sobre relações sociais e meio ambiente. Sugere-se que os profissionais da área da saúde estejam aptos a reconhecer e saber diferenciar os sintomas de fadiga central dos sintomas de depressão, para que possam encaminhar os pacientes, no caso de depressão, também para o serviço psicológico e melhorar a qualidade de vida destes pacientes.

Neuromuscular disorders are understood as diseases affecting the motor unit, and in young children most of these diseases are genetic conditions. Neuromuscular disorder leads to pulmonary and motor function involvement causing central muscular fatigue. The quality of life is considered an important indicator of prognostic and evolution of neuromuscular disorder, and it is used to evaluate the possibility to get ill, and also as an important indicator of patient’s treatment benefits. The study aimed at evaluating central fatigue and its impact in quality of life patients with neuromuscular disorders. It was carried out an evaluation with the following items: age, time of diagnosis, functioning, espirometry, maximal inspiratory and expiratory flow, fatigue severity scale, muscular performance and a questionnaire about quality of life. It was observed that patients did not present symptoms of fatigue but, instead, symptoms of depression as reported in social relationship and environment on quality of life evaluation. We suggest that health professionals should be apt to recognize symptoms of central fatigue in order to differentiating from depression symptoms so that they will be able to conduct patients to the right treatment and improve patients’ quality of life.