阻断NMDA受体可增强皮质酮对海马脑源性神经营养因子表达的抑制cAMP反应元件结合蛋白的作用.pdfVIP

Acta Physiologica Sinica, October 25, 2005, 57 (5): 537-544 537 NMDA cAMP * 200032 (brain-derived neurotrophic factor, BDNF) BDNF mRNA N - -D - (N -methyl-D- aspartate NMDA)MK801 2 mg/kg 3 h BDNF mRNA MK801 (0.1 mg/kg)MK801 30 min cAMP (cAMP response element binding protein CREB)MK801 CREB (P0.05) CREB BDNF NMDA BDNF ; NM DA M K8 01 cAMP Q593+ .2; Q7; R74 Blockade of NMDA receptor enhances corticosterone-induced downregulation of brain-derived neurotrophic factor gene expression in the rat hippocampus through cAMP response element binding protein pathway FENG Hao, LU Li-Min, HUANG Ying, ZHU Yi-Chun, YAO Tai* Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Abstract: High concentration of corticosterone leads to morphological and functional impairments in hippocampus, ranging from a reversible atrophy of pyramidal CA3 apical dendrites to the impairment of long-term potentiation (LTP) and hippocampus-dependent learning and memory. Glutamate and N -methyl-D- aspartate (NMDA) receptor play an important role in this effect. Because of the importance of brain-derived neurotrophic factor (BDNF) in the functions of the hippocampal neurons, alteration of the expression of BDNF is thought to be involved in the corticosterone effect on the hippocampus. To determine whether change in BDNF in the hippocampus is involved in the corticosterone effect, we injected corticosterone (2 mg/kg, s.c.) to Sprague-Dawley rats and measured the mRNA, proBDNF and mature BDNF protein levels in the hippocampus. We also measured the phosphorylation level of the transcription factor cAMP response element binding protein (CREB). Furthermore, we intraperitoneally injected NMDA receptor antagonist MK801 (0.1 mg/kg) 30 min before corticosterone administration to investigate