Shughrue P J, Dorsa D M
Department of Pharmacology, University of Washington, Seattle 98195.
J Comp Neurol. 1994 Feb 8;340(2):174-84. doi: 10.1002/cne.903400204.
GAP-43 is a membrane-bound protein selectively concentrated in axonal growth cones during brain development and implicated in axonal outgrowth and elongation. A sex dimorphism in the number of synapses in certain regions of the adult rat brain has been attributed to differences in gonadal steroid hormone action during early postnatal life. The results of recent studies have demonstrated that gonadal steroids modulate GAP-43 mRNA in regions of the postnatal and adult brain where steroid hormone receptors are concentrated. Since gonadal steroids influence the development of the sexually undifferentiated brain during the first few weeks of postnatal life, the present study investigated the ontogeny of GAP-43 mRNA in the male and female rat brain between postnatal days 1 and 25. On postnatal days 1, 3, 6, 12, 18, and 25, brains were collected from male and female postnates and frozen, and 16 microns cryostat sections were processed and hybridized with a 35S-labeled antisense riboprobe complementary to GAP-43 mRNA. Evaluation of film autoradiograms demonstrated a widespread distribution of GAP-43 mRNA in postnatal brain regions, including the cerebral cortex; bed nucleus of the stria terminalis; and medial preoptic area, ventromedial nucleus, and arcuate nucleus of the hypothalamus. Densitometric measurements revealed that GAP-43 mRNA was transiently elevated during early postnatal life, with a subsequent decrease during brain maturation, although the pattern of change varied among the brain regions investigated. In addition, the level of GAP-43 hybridization signal was significantly higher in the male cortex, bed nucleus, and medial preoptic nucleus, but not the ventromedial and arcuate nuclei, than in postnatal females. Analysis of slide autoradiograms demonstrated that the change in GAP-43 mRNA during postnatal development was due to changes at the cellular level. The present results indicate that expression of GAP-43 mRNA is transiently elevated and sexually dimorphic in certain regions of the early postnatal rat brain. The results further suggest that the differential expression of GAP-43 in the male and female postnatal brain may be related to sex differences in neuronal outgrowth and connectivity resulting in a dimorphism in the pattern of adult neuronal circuitry.
GAP - 43是一种膜结合蛋白，在大脑发育过程中选择性地集中于轴突生长锥，与轴突的生长和延伸有关。成年大鼠大脑某些区域突触数量的性别差异归因于出生后早期性腺类固醇激素作用的差异。最近的研究结果表明，性腺类固醇在出生后和成年大脑中类固醇激素受体集中的区域调节GAP - 43 mRNA。由于性腺类固醇在出生后最初几周影响未分化性别的大脑发育，本研究调查了出生后第1天至第25天雄性和雌性大鼠大脑中GAP - 43 mRNA的个体发生。在出生后第1、3、6、12、18和25天，从雄性和雌性幼崽中采集大脑并冷冻，制作16微米的冰冻切片，用与GAP - 43 mRNA互补的35S标记反义核糖探针进行处理和杂交。对胶片放射自显影片的评估表明，GAP - 43 mRNA在出生后脑区广泛分布，包括大脑皮层、终纹床核以及下丘脑的内侧视前区、腹内侧核和弓状核。密度测量显示，GAP - 43 mRNA在出生后早期短暂升高，随后在大脑成熟过程中下降，尽管在所研究的脑区中变化模式有所不同。此外，雄性皮层、终纹床核和内侧视前核中GAP - 43杂交信号水平显著高于出生后的雌性，但腹内侧核和弓状核除外。对载玻片放射自显影片的分析表明，出生后发育过程中GAP - 43 mRNA的变化是由于细胞水平的变化。目前的结果表明，GAP - 43 mRNA的表达在出生后早期大鼠大脑的某些区域短暂升高且具有性别差异。结果进一步表明，出生后雄性和雌性大脑中GAP - 43的差异表达可能与神经元生长和连接的性别差异有关，从而导致成年神经元回路模式的二态性。
