RESUMO

Failure in energy metabolism and oxidative damage are associated with Huntington's disease (HD). Ascorbic acid released during synaptic activity inhibits use of neuronal glucose, favouring lactate uptake to sustain brain activity. Here, we observe a decreased expression of GLUT3 in STHdhQ111 cells (HD cells) and R6/2 mice (HD mice). Localisation of GLUT3 is decreased at the plasma membrane in HD cells affecting the modulation of glucose uptake by ascorbic acid. An ascorbic acid analogue without antioxidant activity is able to inhibit glucose uptake in HD cells. The impaired modulation of glucose uptake by ascorbic acid is directly related to ROS levels indicating that oxidative stress sequesters the ability of ascorbic acid to modulate glucose utilisation. Therefore, in HD, a decrease in GLUT3 localisation at the plasma membrane would contribute to an altered neuronal glucose uptake during resting periods while redox imbalance should contribute to metabolic failure during synaptic activity.

Assuntos

Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Transportador de Glucose Tipo 3/metabolismo , Doença de Huntington/patologia , Neurônios/patologia , Estresse Oxidativo , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Western Blotting , Membrana Celular/metabolismo , Células Cultivadas , Feminino , Imunofluorescência , Glucose/metabolismo , Transportador de Glucose Tipo 3/genética , Doença de Huntington/genética , Doença de Huntington/metabolismo , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oxirredução , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa