RESUMEN

Recent studies suggest that glutamate plays a pivotal role in the processing of sensory information in the spinal cords of patients with diabetic neuropathy. However, the specific glutamate receptors that that are involved have yet to be determined. We therefore conducted a study to characterize the expression of messenger RNAs (mRNAs) coding for subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors and N-methyl-d-aspartate (NMDA) receptors and for metabotropic glutamate receptors (mGluRs) in the dorsal horn of the lumbar segment of the spinal cord in a rat model (streptozotocin [STZ]-induced) of diabetic neuropathy. The levels of mRNAs coding for AMPA receptor subunits, GluR1, GluR2, and GluR3, were significantly increased in all layers (laminae I-V) of the dorsal horn in diabetic (STZ-injected) rats compared to control (vehicle-injected) rats. The hybridization signals for NR2A mRNA and NR2B mRNA were significantly elevated in the deep layer of the dorsal horn of diabetic rats. In diabetic (STZ-induced) rats, the levels of expression of mGluR1 mRNA and mGluR5 mRNA were significantly increased in all layers of the dorsal horn. These results suggest that abnormal expression of multiple glutamate receptors is involved in the development of diabetic neuropathy and that glutamate receptors are promising targets in the treatment of this disorder.

Asunto(s)

Diabetes Mellitus Experimental/metabolismo , Células del Asta Posterior/metabolismo , Receptores AMPA/metabolismo , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Autorradiografía/métodos , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/genética , Modelos Animales de Enfermedad , Masculino , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores AMPA/clasificación , Receptores AMPA/genética , Receptores de Glutamato/clasificación , Receptores de Glutamato/genética , Receptores de Glutamato Metabotrópico/clasificación , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de N-Metil-D-Aspartato/clasificación , Receptores de N-Metil-D-Aspartato/genética , Médula Espinal/patología , Estreptozocina , Factores de Tiempo , Regulación hacia Arriba/fisiología