Brain Regions Responding to Endogenous Prolactin during Pregnancy and Lactation

Prolactin;Brain;Pregnancy;Post-partum;Anxiety;Depression

McFadden, Sarah Louise ; Larsen, Caroline ; Grattan, Dave

University of Otago

关键词: Prolactin;    Brain;    Pregnancy;    Post-partum;    Anxiety;    Depression;   

Others  :  https://ourarchive.otago.ac.nz/bitstream/10523/4080/1/McFaddenSara2013BBioMedSc%28Hons%29

美国|英语

来源: Otago University Research Archive

【 摘 要 】

There is an increased incidence of dysfunctional mood disorders postpartum, affecting approximately 10-20% of all women. Postpartum mood disorders can have devastating effects on the mother, and lead to altered relationships with offspring, an increased incidence of child abuse, and increased conflict in relationships leading to a higher rate of separation.It has been discovered that low levels of prolactin during early pregnancy prevent the normal increase in neurogenesis in the subventricular zone (SVZ) from occurring, resulting in markedly increased anxiety postpartum in mice. However, it has been observed that the SVZ does not express prolactin receptor mRNA, nor prolactin-induced phosphorylation of the transcription factor STAT5 (pSTAT5), a marker of prolactin mediated signal transduction. Therefore, we hypothesized that the normal elevation of prolactin that occurs in early pregnancy initiates changes in other areas of the maternal brain that indirectly lead to increased neurogenesis in the SVZ. The aim of this study was to characterize which areas of the brain are activated in response to the normal surges of prolactin that occur during early pregnancy, and also if there is a difference in the regions of the brain that are activated during pregnancy and in the postpartum period. A group of mice were killed on day 3 of pregnancy at a time when prolactin levels were low, and another group of mice were killed during a surge when prolactin levels were high. Two groups of mice were also killed on day 7, one at a time when prolactin was low, and the other when prolactin was high. The final two groups were killed on postpartum day 4; one group had been exposed to pups, and the other had not. Using immunohistochemistry we analyzed levels of pSTAT5 throughout the mouse brain.We found that expression of pSTAT5 was significantly increased when prolactin levels were high compared to when they were low during pregnancy. Expression of pSTAT5 was seen in regions of the brain known to be crucial for regulation of mood and behaviour, such as the medial preoptic area, and also in the Arcuate nucleus and the VMH (ventromedial hypothalamic nucleus). In the lactating mice, a higher expression of pSTAT5 was seen in these areas, as well as in additional areas not seen during pregnancy, such as the Bed Nucleus of the Stria Terminalis, the Amygdala and the Dorsomedial Hypothalamic Nucleus. These areas may be areas necessary for maternal behaviours at the time of lactation.We also stained for c-fos, a marker of early gene activation in neurons to establish if there were nuclei that are indirectly responding to prolactin. The c-fos data showed that it was not a good marker for prolactin activation, but it was able to show areas of the brain important for maternal behaviour.In conclusion, this study confirmed that prolactin does not activate pSTAT5 in the sub ventricular zone during pregnancy, consistent with the hypothesis that prolactin induced increase in neurogenesis in this area is mediated indirectly. We identified the MPA, the arcuate and the VMH as the major areas responsive to endogenous prolactin in early pregnancy. Moreover, we found that there were more prolactin-responsive areas in the maternal brain during lactation.