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Department of Physiology, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
¹ School of Nursing, Mei-Ho Institute of Technology, Pingtung, Taiwan

(Requests for offprints should be addressed to C Hsu; Email: chinhsu{at}kmu.edu.tw)

The present study was designed to identify possible signaling pathways, which may play a role in prevention of neuronal apoptosis in the sexually dimorphic nucleus of the preoptic area (SDN-POA) after physiological activation of the N-methyl-D-aspartate (NMDA) receptor. Gene response to the blockage of the NMDA receptor by an antagonist (dizocilpine hydrogen maleate; MK-801) was screened after suppression subtractive hybridization (SSH). The results showed that dfferential screening after SSH detected the presence of some neurotrophic genes (RNA binding motif protein 3 (RBM3), -tubulin) as well as apoptosis-related genes (Bcl-2, cytochrome oxidase subunit II, cytochrome oxidase subunit III) in the SDN-POA of male rats, which were down-regulated by blocking the NMDA receptor. The RT-PCR products of the aforementioned genes in MK-801-treated males were significantly less than that in untreated males. In particular, the expression of Bcl-2 mRNA, including Bcl-2 protein, in male rats were significantly suppressed by MK-801 treatment. Moreover, the binding activity of nuclear factor B (NFB) was significantly higher in male rats than in females, but significantly diminished by blocking the NMDA receptor with MK-801 in male rats. No significant difference in cAMP response element-binding protein (CREB) binding activity was observed among untreated male, MK-801-treated male, untreated female and MK-801-treated female groups. These results suggest that genes regulated by NMDA receptor activation might participate in neuronal growth and/or anti-apoptosis, and support an important signaling pathway of NFB activation and its target gene, Bcl-2, in preventing neuronal apoptosis in the SDN-POA of male rats during sexual development.

This article has been cited by other articles:

				T.-Y. Lee, K.-L. Tsai, W.-S. Lee, and C. Hsu The molecular events occur during MK-801-induced cytochrome oxidase subunit II down-regulation in GT1-7 cells J. Mol. Endocrinol., July 1, 2007; 39(1): 53 - 66. [Abstract] [Full Text] [PDF]

				J. C. de Rivero Vaccari, G. P. Casey, S. Aleem, W.-M. Park, and R. A. Corriveau NMDA receptors promote survival in somatosensory relay nuclei by inhibiting Bax-dependent developmental cell death PNAS, November 7, 2006; 103(45): 16971 - 16976. [Abstract] [Full Text] [PDF]