生长激素对发育早期兴奋性和抑制性突触传递的调控

The normal functioning of the brain relies on its intricate and complex circuits. The laboratory in which applicant join has been studying the mechanism of regulating the development of nerve circuits in the cerebral cortex for a long time. Recent work has found that excitatory synaptic transmission of pyramidal neurons in sensory cortex were quickly regulated by the neuropeptides oxytocin and cytokine CCL2, both of them are not affect inhibitory synaptic transmission. The applicant recent have found that growth hormone regulate synaptic transmission of pyramidal neurons both in the sensory cortex and hippocampus changed with the development process. The results showed that rhGH promotes excitatory synaptic transmission in both L2/3 pyramidal neurons of the primary somatosensory cortex (S1) and hippocampal CA1 pyramidal neurons, at postnatal day 14 (P14) and P21, Inhibitory synaptic transmission was only affected by rhGH at P21, but not at P14, in both cell types. The primary data suggest that growth hormone, a peptide hormone that has a decisive effect on the growth and development of individuals after birth, has a key regulation on the early development of the nervous system and the normal maintenance of brain function. Therefore, we assume that the regulation of growth hormone on the timing differences of neuronal excitability and inhibitory synaptic transmission plays an important role in neural circuits plasticity at the early stage of development. The study is expected to provide a basis for revealing the neurological mechanisms by which growth hormone regulates synaptic transmission and neural loop development in cognitive-related brain regions.

大脑的正常认知功能依赖于其复杂而精细的神经网络。申请人所在研究组长期研究调控大脑皮层神经环路发育的机制，近期工作发现神经肽催产素和细胞因子CCL2可快速调控感觉皮层椎体神经元的兴奋性突触传递，但不影响抑制性突触传递。申请人近期的研究发现生长激素对感觉皮层和海马的椎体神经元突触传递的调控随发育进程改变：在出生后14天的小鼠（P14）脑中只上调兴奋性突触传递；在P21的小鼠脑中同时增加兴奋性和抑制性突触传递。预实验结果提示，生长激素这一在个体出生后的生长和发育起决定性影响的肽类激素对神经系统早期发育与脑功能的正常维持具有关键的调控作用。因此，我们假设生长激素对神经元兴奋性和抑制性突触传递时序差异性的调控在发育早期神经环路可塑性中发挥重要作用。该研究有望为揭示生长激素在出生后早期调控认知相关脑区的突触传递、神经环路发育的神经机制提供依据。

生长激素是对个体出生后的生长和发育起决定性影响的一种肽类激素，主要由垂体前叶的生长激素细胞（somatotropes）合成和分泌并以脉冲式的方式释放入血 。对生长激素及其临床应用于治疗由生长激素缺乏所引起的生长发育迟缓的研究已逾百年；并且，生长激素的替代疗法，重组人生长激素（recombinant human Growth Hormone , rhGH）也已用于治疗儿童期发病的生长激素分泌不足所诱发的身材矮小和智力发育迟缓。申请人近期的研究发现生长激素对感觉皮层和海马的椎体神经元突触传递的调控随发育进程改变：在出生后14天的小鼠（P14）脑中只上调兴奋性突触传递；在P21的小鼠脑中同时增加兴奋性和抑制性突触传递。此外，大脑的正常认知功能依赖于其复杂而精细的神经网络。申请人最新的研究发现，生长激素能够在抑制性突触传递形成的高峰显著的促进小鼠大脑皮层神经网络的兴奋-抑制平衡。实验结果提示，生长激素这一在个体出生后的生长和发育起决定性影响的肽类激素对神经系统早期发育与脑功能的正常维持具有关键的调控作用。因此，我们假设生长激素对神经元兴奋性和抑制性突触传递时序差异性的调控在发育早期神经环路可塑性中发挥重要作用。相关研究成果发表在了Acta Pharmacological Sinica 上。该研究有望为揭示生长激素在出生后早期调控认知相关脑区的突触传递、神经环路发育的神经机制提供依据。