Astrocytic Modulation of Supraoptic Oxytocin Neuronal Activity in Rat Dams with Pup-Deprivation at Different Stages of Lactation

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) inWestern blotswhile 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 mu mol/L, 5 min before oxytocin). In addition, inhibition of AQP4 with TGN-020 blocked excitation in oxytocin neurons evoked by prostaglandin E-2, 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.

Automated summary

Appropriate interactions between astrocytes and oxytocin neurons are essential for normal lactation. Intermittent pup-deprivation led to decreased suckling duration and litter's body weight gain, associated with increased expressions of GFAP and AQP4 in astrocytes. Oxytocin treatment reduced the length of GFAP filaments and AQP4 puncta while increasing GFAP staining, indicating the importance of AQP4-associated astrocytic plasticity in regulating oxytocin neuronal activity during lactation.