Is Prolactin Action on Forebrain Neurons During Pregnancy Important for Maternal Neurogenesis and Behaviours?
Cashen, Sarah Christina
Pregnancy is associated with a dramatic increase in serum prolactin levels that is essential for the normal increase in neurogenesis in the maternal brain, and for the associated expression of maternal behaviours after birth. As yet, it is not known which neurons prolactin acts on in the maternal brain to induce these changes, but it has been shown that prolactin receptors are present on GABAergic neurons in forebrain nuclei implicated in the regulation of maternal behaviour. This study aimed to examine the effect that prolactin action on forebrain neurons has on expression of maternal behaviour and on levels of neurogenesis, employing conditional deletion of the prolactin receptor using cre-lox technology. This technology allowed the creation of mice with prolactin receptors removed from CaM kinase II containing neurons (most forebrain neurons; CKC mice), and more specifically from neurons containing the vesicular GABA transporter (vGAT mice). When cre positive mice and controls (wildtype C57BL/6J and cre negative mice), were reproductively mature (6-8 weeks old), some mice were placed in individual cages and mated with a stud male. Neurogenesis was assessed on day seven of pregnancy, using injections of BrdU, which labels newly dividing cells. Other groups of mice were allowed to continue the pregnancy until term, and the day of parturition was designated as postpartum day one (PPD1). Maternal behaviour was tested on PPD2 by placing the mouse and three pups in a clean novel cage and observing all behaviours. On PPD3 maternal behaviour was tested in a similar manner in the home cage. Mice were also tested for anxiety on PPD4 in the light-dark box. Both CKC and vGAT cre positive mice showed significantly impaired maternal behaviour in the home cage compared with control mice, but the impairment was greater in the CKC positive mice than the vGAT cre positive mice. While all mice showed impairment in the novel cage, maternal behaviour was once again significantly more impaired in the CKC positive mice. CKC positive mice mostly ignored the pups, but at times were aggressive towards them, either eating pups before, or after death. Consequently, pup survival was dramatically reduced in CKC cre positive mice, compared with controls. There was no difference in levels of anxiety between the groups postpartum, suggesting that prolactin acts elsewhere to exert the postpartum anxiolytic effect. Surprisingly, given the maternal behaviour results, the levels of neurogenesis on day seven of pregnancy in the transgenic mice were not reduced as expected. There was no significant decrease in neurogenesis in either cre positive group compared with the controls. These findings suggest that prolactin acts through receptors on GABAergic neurons to stimulate some aspects of maternal behaviour, but other neurons must also contribute, and that prolactin acts somewhere other than forebrain neurons to induce neurogenesis.
Advisor: Larsen, Caroline; Grattan, Dave
Degree Name: Bachelor of Medical Science with Honours
Degree Discipline: Anatomy
Publisher: University of Otago
Keywords: prolactin; neurogenesis; rodent; forebrain; pregnancy
Research Type: Thesis