ABSTRACT
BACKGROUND AND OBJECTIVES: The p-CREB (phospholyated form of cAMP/calcium response element binding protein) was known to be one of transcription factors for immediate early genes in the brain stem nuclei. The purpose of this present study was to evaluate time-dependent expression of p-CREB and investigate the effect of MK801, non-competitive NMDA channel blocker, on p-CREB expression following unilateral labyrinthectomy (ULX). MATERIALS AND METHODS: Adult Sprague-Dalwey rats weighing 250-300 g were divided into a control group and an unilateral labyrinthetomy (ULX) group. The intraperitoneal injection of MK801 was administered either 30 min before or 24 hrs after ULX. The ABC immunohistochemical staining and digital image analysis system were used to measure the p-CREB expression in neuronal cells. RESULTS: The peak level of p-CREB expressions in 4 major vestibular nuclei was observed bilaterally with the other brain stem nuclei including reticular formation and olivary complex at 30 min following ULX. Thereafter, the p-CREB immunoreactivity in these nuclei was reduced rapidly to the control level for 6 hrs after ULX. Treatment of MK801 for 30 min preceding ULX decreased p-CREB immunoreactivity significantly in both the injured and intact sides of the 4 major vestibular nuclei with dose-dependent relationship. However, MK801 did not affect the change of p-CREB immunoreactivity in bilateral vestibular complex 24 hrs after ULX. CONCLUSION: These results suggest that cAMP/calcium response element binding protein plays an important role in the initial events of vestibular compensation in which its activity is in part regulated by NMDA receptor.