Penix Jonathon, DeFazio R Anthony, Dulka Eden A, Schnell Santiago, Moenter Suzanne M
Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
R Soc Open Sci. 2020 Aug 12;7(8):201040. doi: 10.1098/rsos.201040. eCollection 2020 Aug.
Gonadotropin-releasing hormone (GnRH) neurons form the final pathway for the central neuronal control of fertility. GnRH is released in pulses that vary in frequency in females, helping drive hormonal changes of the reproductive cycle. In the common fertility disorder polycystic ovary syndrome (PCOS), persistent high-frequency hormone release is associated with disrupted cycles. We investigated long- and short-term action potential patterns of GnRH neurons in brain slices before and after puberty in female control and prenatally androgenized (PNA) mice, which mimic aspects of PCOS. A Monte Carlo (MC) approach was used to randomize action potential interval order. Dataset distributions were analysed to assess (i) if organization persists in GnRH neuron activity , and (ii) to determine if any organization changes with development and/or PNA treatment. GnRH neurons in adult control, but not PNA, mice produce long-term patterns different from MC distributions. Short-term patterns differ from MC distributions before puberty but become absorbed into the distributions with maturation, and the distributions narrow. These maturational changes are blunted by PNA treatment. Firing patterns of GnRH neurons in brain slices thus maintain organization dictated at least in part by the biologic status of the source and are disrupted in models of disease.
促性腺激素释放激素(GnRH)神经元构成了生育能力中枢神经控制的最终通路。GnRH以脉冲形式释放,其频率在女性中有所变化,有助于驱动生殖周期的激素变化。在常见的生育障碍多囊卵巢综合征(PCOS)中,持续的高频激素释放与月经周期紊乱有关。我们研究了雌性对照小鼠和模拟PCOS某些方面的产前雄激素化(PNA)小鼠在青春期前后脑片中GnRH神经元的长期和短期动作电位模式。采用蒙特卡罗(MC)方法对动作电位间隔顺序进行随机化。分析数据集分布以评估:(i)GnRH神经元活动中是否存在组织规律;(ii)确定是否有任何组织规律随发育和/或PNA处理而变化。成年对照小鼠而非PNA小鼠的GnRH神经元产生与MC分布不同的长期模式。短期模式在青春期前与MC分布不同,但随着成熟被纳入分布中,且分布变窄。这些成熟变化因PNA处理而减弱。因此,脑片中GnRH神经元的放电模式维持着至少部分由来源的生物学状态决定的组织规律,并且在疾病模型中受到破坏。