Site-Specific Changes in Brain Extra-SCN Oscillators during Early Pregnancy in the Rat

Abstract

The influence of circadian timekeeping systems on behavior and physiology can change substantially as female mammals undergo the transition from a nonpregnant to a pregnant state. Here, we examined the possibility that site-specific changes in extra-SCN oscillators and in local rhythms might coincide with the emergence of new patterns of temporal organization among various behavioral and physiological rhythms. Specifically, we compared daily patterns of immunoreactive FOS and PER2 in 3 brain regions of pregnant and diestrous rats. We found that, in the oval nucleus of the bed nucleus of the stria terminalis (BnST-ov), the peak of the PER2 rhythm occurred approximately 12 hours out of phase in pregnant and diestrous females. In contrast, the phase of the rhythm in FOS was the same, but pregnant rats expressed more FOS in the BnST-ov than diestrous ones. In the central amygdala (CEA) of diestrous females, PER2 expression was arrhythmic, but Fos expression was elevated at night. No rhythms were seen in this region of pregnant females, nor were any rhythms seen in the basolateral amygdala of either group. Overall, the patterns in the BnST-ov and the CEA were consistent with the hypothesis that differential changes in daily rhythms within some extra-SCN brain regions might mediate the changes in the temporal organization of several behavioral and endocrine functions that occur during the transition from a nonpregnant to a pregnant state.

Pregnancy affects FOS rhythms in brain regions regulating sleep/wake state and body temperature in rats

“…The findings of the present study, along with those from our previous work (Schrader et al, 2010, 2011), are consistent with the hypothesis that the suite of changes in overt rhythms during early pregnancy in the rat are due to differential changes in rhythmic activity in different brain regions. Thus, pregnancy appears to induce a re-organization of the circadian system of the brain and how it interacts with brain regions that are responsible for different behavioral and homeostatic functions.…”

“…We have documented altered rhythms in protein expression in specific components of the circadian system of the brain in early pregnant rats, as compared to diestrous females (Schrader et al, 2010, 2011). This circadian system includes a primary circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus (Moore and Eichler, 1972; Ralph et al, 1990; Rusak, 1977; Stephan and Zucker, 1972), as well as various extra-SCN oscillators (Guilding and Piggins, 2007; Hastings et al, 2003; Reppert and Weaver, 2002; Weinert, 2005).…”

“…The SCN and extra-SCN oscillators contain rhythmic cells that have a molecular transcription/translation loop that takes approximately 24 h to complete (Bell-Pedersen et al, 2005; Dunlap, 1999; Reppert and Weaver, 2002). The phase of the rhythm in expression of the protein Period2 (PER2), a key component of the molecular oscillator, is altered in both the SCN and some extra-SCN oscillators during early pregnancy in the rat (Schrader et al, 2010, 2011). Additionally, expression of FOS, the protein product of the immediate early gene cfos that often rises after neuronal activation (Kovacs, 2008), is elevated during the mid-light phase in the SCN and at other times in some extra-SCN oscillators in early pregnant rats (Schrader et al, 2010, 2011).…”

“…The phase of the rhythm in expression of the protein Period2 (PER2), a key component of the molecular oscillator, is altered in both the SCN and some extra-SCN oscillators during early pregnancy in the rat (Schrader et al, 2010, 2011). Additionally, expression of FOS, the protein product of the immediate early gene cfos that often rises after neuronal activation (Kovacs, 2008), is elevated during the mid-light phase in the SCN and at other times in some extra-SCN oscillators in early pregnant rats (Schrader et al, 2010, 2011). These data indicate that circadian outputs to systems regulating overt functions, such as the sleep/wake and temperature cycles, may be changing with the transition from the non-pregnant state to pregnancy.…”

The neuroendocrine control of the circadian system: Adolescent chronotype

“…In contrast, gonadectomized males have significantly dampened PER2 rhythms [147], and early pregnancy increases the amplitude of both PER2 and FOS rhythms. Early pregnancy also produces a large 8-12 hr phase shift in PER2 rhythms in the BNST [170]. Other brain regions show more subtle changes in response to gonadal hormone fluctuation.…”