Lehman M N, Coolen L M, Goodman R L, Viguié C, Billings H J, Karsch F J
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521, USA.
Reprod Suppl. 2002;59:149-65.
Seasonally breeding mammals display an annual cycle of fertility that is associated with both structural neuroplasticity and functional changes in the activity of the GnRH neurones in the brain. Sheep are valuable models for understanding the hormonal and environmental cues that regulate seasonal reproduction, as well as the brain circuitry that underlies this response. As a result of the large size of sheep, we can tightly correlate the anatomy of GnRH cells and their patterns of gene expression with direct measurements of their neurosecretory output. Tract tracing studies have begun to reveal the pathways by which seasonal changes in response to oestradiol negative feedback affect the function of the reproductive system. Electron microscopic studies have shown that synaptic inputs on to ovine GnRH cells undergo marked seasonal rearrangements that are independent of hormonal changes and may reflect the intrinsic seasonality of the brain. Recent work indicates that the polysialylated form of neural cell adhesion molecule (PSA-NCAM), a marker of neuroplasticity, is well positioned anatomically to contribute to seasonal structural and functional alterations. Applying state-of-the-art neuroanatomical techniques to this model has allowed us to delineate the neural pathways responsible for the seasonal shut down of reproduction in sheep, as well as to begin to uncover the cellular mechanisms underlying seasonal neuroplasticity in the adult mammalian brain.
季节性繁殖的哺乳动物表现出一年一度的生育周期,这与大脑中促性腺激素释放激素(GnRH)神经元活动的结构神经可塑性和功能变化有关。绵羊是理解调节季节性繁殖的激素和环境线索以及这种反应背后的脑回路的有价值模型。由于绵羊体型较大,我们可以将GnRH细胞的解剖结构及其基因表达模式与它们神经分泌输出的直接测量紧密关联起来。示踪研究已开始揭示对雌二醇负反馈的季节性变化影响生殖系统功能的途径。电子显微镜研究表明,绵羊GnRH细胞上的突触输入经历显著的季节性重排,这些重排独立于激素变化,可能反映了大脑内在的季节性。最近的研究表明,神经可塑性标志物神经细胞黏附分子的多唾液酸化形式(PSA-NCAM)在解剖学上处于有利位置,有助于季节性结构和功能改变。将最先进的神经解剖学技术应用于这个模型,使我们能够描绘出绵羊季节性繁殖停止所涉及的神经通路,并开始揭示成年哺乳动物大脑中季节性神经可塑性的细胞机制。