大鼠腰脊髓中雄激素敏感运动神经元中脑源性神经营养因子(BDNF)mRNA 异构体的差异表达和调控。
Differential expression and regulation of brain-derived neurotrophic factor (BDNF) mRNA isoforms in androgen-sensitive motoneurons of the rat lumbar spinal cord.
机构信息
Northern Michigan University, Department of Biology, 1401 Presque Isle Avenue, Northern Michigan University, Marquette, MI 49855, United States.
出版信息
Mol Cell Endocrinol. 2010 Oct 26;328(1-2):40-6. doi: 10.1016/j.mce.2010.07.001. Epub 2010 Jul 17.
Castration of adult male rats causes dendrites of the spinal nucleus of the bulbocavernosus (SNB) to retract. The neurotrophin brain-derived neurotrophic factor (BDNF) is implicated in mediating these androgenic effects on SNB dendrites. We previously found that castration decreases BDNF mRNA in SNB somata and BDNF protein in proximal SNB dendrites, effects not observed in nearby retrodorsolateral (RDLN) motoneurons. Given that different 5' non-coding exons of BDNF dictate specific subcellular targeting of BDNF mRNA, we set out to identify the specific BDNF transcripts regulated by androgens in SNB motoneurons. We used in situ hybridization to monitor the expression pattern of BDNF transcripts containing non-coding exons I, II, IV, and VI in SNB and RDLN motoneurons in gonadally intact and castrated male rats. While androgen-insensitive RDLN motoneurons expressed all four isoforms, SNB motoneurons contained low levels of BDNF exon IV and little, if any, BDNF exon I. Expression of BDNF isoforms containing exon II and VI was comparable in the two groups of motoneurons. Two weeks after castration, BDNF isoforms containing exon VI were significantly decreased in SNB motoneurons in an androgen-dependent manner, but unaffected in RDLN motoneurons. Because exon VI promotes dendritic localization of BDNF mRNA in other systems, androgens may regulate the dendrites of SNB motoneurons by altering expression of BDNF isoforms, thereby impairing targeting of BDNF protein to dendrites to regulate local synaptic signaling and dendritic structure.
去势成年雄性大鼠会导致球海绵体神经核(SNB)的树突回缩。神经营养因子脑源性神经营养因子(BDNF)被认为在介导 SNB 树突的这些雄激素作用中起作用。我们之前发现,去势会减少 SNB 体细胞核内的 BDNF mRNA 和近侧 SNB 树突内的 BDNF 蛋白,而在附近的背外侧(RDLN)运动神经元中则没有观察到这种现象。鉴于 BDNF 的不同 5'非编码外显子决定了 BDNF mRNA 的特定亚细胞靶向,我们着手确定雄激素调节 SNB 运动神经元中 BDNF 的特定转录本。我们使用原位杂交技术监测含有非编码外显子 I、II、IV 和 VI 的 BDNF 转录本在 SNB 和 RDLN 运动神经元中的表达模式,这些运动神经元存在于性腺完整和去势雄性大鼠中。虽然雄激素不敏感的 RDLN 运动神经元表达所有四种同工型,但 SNB 运动神经元中 BDNF 外显子 IV 的含量较低,几乎没有 BDNF 外显子 I。两组运动神经元中 BDNF 同工型的表达模式相似。去势 2 周后,SNB 运动神经元中含有外显子 VI 的 BDNF 同工型以雄激素依赖的方式显著减少,但在 RDLN 运动神经元中不受影响。因为外显子 VI 促进其他系统中 BDNF mRNA 的树突定位,雄激素可能通过改变 BDNF 同工型的表达来调节 SNB 运动神经元的树突,从而损害 BDNF 蛋白向树突的靶向定位,以调节局部突触信号和树突结构。