Appropriate interactions between astrocytes and oxytocin neurons in the hypothalamo- neurohypophysial system are essential for normal lactation. To further explore the mechanisms underlying astrocytic modulation of oxytocin neuronal activity, we observed astrocytic plasticity in the supraoptic nucleus of lactating rats with intermittent pup-deprivation (PD, 20 h/day) at early (day 1–5) and middle (day 8–12) stages of lactation. PD at both stages decreased suckling duration and litter’s body weight gain. They also significantly increased the expression of glial fibrillary acidic protein (GFAP) in Western blots while increased GFAP filaments and the colocalization of GFAP filaments with aquaporin 4 (AQP4) puncta in astrocyte processes surrounding oxytocin neuronal somata in immunohistochemistry in the supraoptic nucleus. Suckling between adjacent milk ejections but not shortly after them decreased molecular association between GFAP and AQP4. In hypothalamic slices from male rats, oxytocin treatment (0.1 nmol/L, 10 min) significantly reduced the length of GFAP filaments and AQP4 puncta in the processes but increased GFAP staining in the somata. These oxytocin effects were blocked by pretreatment of the slices with N-(1,3,4-Thiadiazolyl) nicotinamide (TGN-020, inhibitor of AQP4, 10 µmol/L, 5 min before oxytocin). In addition, inhibition of AQP4 with TGN-020 blocked excitation in oxytocin neurons evoked by prostaglandin E₂, a downstream signal of oxytocin receptor and mediator of oxytocin-evoked burst firing, in whole-cell patch-clamp recordings. These results indicate that AQP4-associated astrocytic plasticity is essential for normal oxytocin neuronal activity during lactation and that PD-evoked hypogalactia is associated with astrocytic process expansion following increased GFAP and AQP4 expressions.

下丘脑神经垂体系统中星形胶质细胞和催产素神经元之间的适当相互作用对于正常哺乳至关重要。为了进一步探讨星形胶质细胞调节催产素神经元活动的机制，我们在早期（第1-5天）和中期（第8天）间歇性幼崽剥夺（PD，20小时/天）的哺乳大鼠视上核中观察到星形胶质细胞的可塑性–12) 哺乳阶段。两个阶段的PD都会减少哺乳时间和窝体重增加。他们还显着增加了蛋白质印迹中胶质纤维酸性蛋白（GFAP）的表达，同时在视上核免疫组织化学中增加了GFAP丝，以及GFAP丝与水通道蛋白4（AQP4）点周围星形胶质细胞突起中的共定位。在相邻的乳汁喷射之间而不是在它们之后不久的哺乳会降低 GFAP 和 AQP4 之间的分子关联。在雄性大鼠下丘脑切片中，催产素处理（0.1 nmol/L，10 分钟）显着缩短了突起中的 GFAP 丝和 AQP4 斑点的长度，但增加了体细胞中 GFAP 的染色。通过用 N-(1,3,4-噻二唑基)烟酰胺（TGN-020，AQP4 抑制剂，10 µmol/L，在催产素前 5 分钟）预处理切片，可以阻断这些催产素作用。此外，在全细胞膜片钳记录中，用 TGN-020 抑制 AQP4 可以阻断前列腺素 E 2 诱发的催产素神经元的兴奋，前列腺素 E ₂是催产素受体的下游信号，也是催产素诱发的突发放电的介体。 这些结果表明，AQP4 相关的星形胶质细胞可塑性对于哺乳期间正常的催产素神经元活动至关重要，并且 PD 诱发的缺乳与 GFAP 和 AQP4 表达增加后的星形胶质细胞过程扩张相关。