Frahm Krystle A, Handa Robert J, Tobet Stuart A
Department of Biomedical Sciences and School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523.
Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, PA 15261.
J Endocr Soc. 2017 Dec 28;2(2):140-153. doi: 10.1210/js.2017-00439. eCollection 2018 Feb 1.
Neurons in the paraventricular nucleus of the hypothalamus (PVN) integrate peripheral signals and coordinate responses that maintain numerous homeostatic functions. An excess of glucocorticoids during fetal development results in long-lasting consequences tied to disrupted PVN development. The PVN contains a distinct neuronal population and a threefold greater vascular density than the surrounding brain regions that prepubertally is reduced in offspring exposed to excess glucocorticoids . This study expands the examination of sex-specific nonneuronal PVN composition by examining astrocytes, astrocytic endfeet, and pericytes. Blood-brain barrier (BBB) competency and composition were examined along with depressive-like behavior and hypothalamic-pituitary-adrenal function in male and female mice. For PVN vasculature, female offspring of vehicle (veh)-treated mothers had significantly more astrocytes and pericytes than male offspring from the same litters. Female offspring from dexamethasone (dex)-treated mothers had significantly lower levels of astrocytes than female offspring from veh-treated mothers, whereas male offspring from dex-treated mothers had greater levels of pericytes compared with veh-treated male offspring. Using the tail-suspension test, male and female offspring from dex-treated mothers had significantly shorter latencies to immobility, indicating an increase in depression-like behavior, and showed greater plasma corticosterone after restraint stress, which was significantly greater in female offspring from dex-treated mothers even after recovery. Therefore, in addition to long-term sex differences in cellular components of the BBB in the PVN that were differentially regulated by fetal glucocorticoid exposure, there were behavioral differences observed into early adulthood in a sex-specific manner.
下丘脑室旁核（PVN）中的神经元整合外周信号并协调维持多种稳态功能的反应。胎儿发育期间糖皮质激素过量会导致与PVN发育中断相关的长期后果。PVN包含独特的神经元群体，其血管密度比周围脑区高三倍，在青春期前，暴露于过量糖皮质激素的后代中这种血管密度会降低。本研究通过检查星形胶质细胞、星形胶质细胞终足和周细胞，扩展了对PVN性别特异性非神经元组成的研究。研究了雄性和雌性小鼠的血脑屏障（BBB）功能和组成，以及抑郁样行为和下丘脑-垂体-肾上腺功能。对于PVN脉管系统，接受载体（veh）处理的母亲所生的雌性后代比同窝雄性后代有更多的星形胶质细胞和周细胞。接受地塞米松（dex）处理的母亲所生的雌性后代的星形胶质细胞水平显著低于接受veh处理的母亲所生的雌性后代，而接受dex处理的母亲所生的雄性后代与接受veh处理的雄性后代相比，周细胞水平更高。使用尾悬测试，接受dex处理的母亲所生的雄性和雌性后代静止不动的潜伏期显著缩短，表明抑郁样行为增加，并且在束缚应激后血浆皮质酮水平更高，即使在恢复后，接受dex处理的母亲所生的雌性后代的血浆皮质酮水平也显著更高。因此，除了PVN中BBB细胞成分存在长期的性别差异，且这种差异受到胎儿糖皮质激素暴露的不同调节外，在成年早期还观察到了性别特异性的行为差异。
