Parkin Catherine, Ortiz Juliet, Cruz Sofia, Bath Kevin G, Romeo Russell D
Department of Neuroscience and Behavior, Barnard College of Columbia University, New York, New York, USA.
Department of Psychiatry, Columbia University, New York, New York, USA.
Dev Neurosci. 2024 Oct 28:1-11. doi: 10.1159/000542277.
Pubertal maturation is marked by significant changes in stress-induced hormonal responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis, with prepubertal male and female rats often exhibiting greater HPA reactivity compared to adult males and females. Though the implications of these changes are unclear, elevated stress responsiveness might contribute to the stress-related vulnerabilities often associated with puberty.
The current experiments sought to determine whether differences in cellular activation, as measured by FOS immunohistochemistry, or excitatory ionotropic glutamate receptor subunit expression, as measured by qRT-PCR, in the paraventricular nucleus (PVN) were associated with these noted pubertal shifts in stress reactivity in male and female rats. As the PVN is the key nucleus responsible for activating the hormonal stress response, we predicted greater cellular activation and higher expression levels of glutamate receptor subunits in the PVN of prepubertal males and females compared to their adult counterparts.
Our FOS data revealed that while prepubertal males showed greater stress-induced activation in the PVN than adult males, prepubertal females showed less activation than adult females. Moreover, many of the NMDA, AMPA, and kainate receptor subunits measured, including Grin1, Grin2b, Gria1, Gria2, Grik1, and Grik2, had higher expression levels in adults, particularly in males.
Though not supporting our initial predictions, these data do indicate that age and stress influence the activation of the PVN and the expression of glutamate receptor subunits important in its function. These data also suggest that the effects of age and stress are different in males and females. Though still far from a clear understanding of what mechanism(s) mediate pubertal shift in stress reactivity, these data add to our growing understanding of how age, stress, and sex influence HPA function.
青春期成熟的标志是下丘脑 - 垂体 - 肾上腺(HPA)轴介导的应激诱导激素反应发生显著变化,青春期前的雄性和雌性大鼠通常比成年雄性和雌性表现出更高的HPA反应性。尽管这些变化的影响尚不清楚,但应激反应性升高可能导致与青春期相关的应激易感性。
当前实验旨在确定通过FOS免疫组织化学测量的细胞激活差异,或通过qRT-PCR测量的室旁核(PVN)中兴奋性离子型谷氨酸受体亚基表达差异,是否与雄性和雌性大鼠应激反应性的青春期变化有关。由于PVN是激活激素应激反应的关键核团,我们预测青春期前的雄性和雌性PVN中的细胞激活程度更高,谷氨酸受体亚基的表达水平也高于成年大鼠。
我们的FOS数据显示,青春期前的雄性大鼠在PVN中的应激诱导激活程度高于成年雄性大鼠,而青春期前的雌性大鼠的激活程度低于成年雌性大鼠。此外,所测量的许多NMDA、AMPA和海人酸受体亚基,包括Grin1、Grin2b、Gria1、Gria2、Grik1和Grik2,在成年大鼠中表达水平更高,尤其是在雄性大鼠中。
尽管不支持我们最初的预测,但这些数据确实表明年龄和应激会影响PVN的激活及其功能中重要的谷氨酸受体亚基的表达。这些数据还表明年龄和应激对雄性和雌性的影响不同。尽管仍远未清楚了解介导应激反应性青春期变化的机制,但这些数据增加了我们对年龄、应激和性别如何影响HPA功能的认识。