Gene regulation by NMDA receptor activation in the SDN-POA neurons of male rats during sexual development.
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 differential screening after SSH detected the presence of some neurotrophic genes (RNA binding motif protein 3 (RBM3), alpha-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 kappaB (NFkappaB) 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 NFkappaB activation and its target gene, Bcl-2, in preventing neuronal apoptosis in the SDN-POA of male rats during sexual development.
Hsu
Hseng-Kuang
HK
Department of Physiology, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
Shao
Pei-Lin
PL
Tsai
Ke-Li
KL
Shih
Huei-Chuan
HC
Lee
Tzu-Ying
TY
Hsu
Chin
C
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015536:Down-Regulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011301:Preoptic Area / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012727:Sex Characteristics; D046468:Sexual Development / Q000502:physiology*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D018691:Excitatory Amino Acid Antagonists; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D016194:Receptors, N-Methyl-D-Aspartate; D014404:Tubulin; D016291:Dizocilpine Maleate