Developmental changes in the hypothalamic mRNA expression levels of PACAP and its receptor PAC1 and their sensitivity to fasting in male and female rats

Abstract

The actions and responses of hypothalamic appetite regulatory and factors change markedly during the neonatal to pre-pubertal period. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been found to play pivotal roles in the regulation of metabolic and nutritional status through its specific receptor PAC1. PACAP/PAC1 have anorectic roles, and their functions are regulated by leptin in adulthood. In the present study, we showed that hypothalamic PACAP mRNA expression decreases during the neonatal to pre-pubertal period (from postnatal day 10-30) in both male and female rats. During this period, hypothalamic PACAP mRNA expression was not affected by 24h fasting in either sex, while the serum leptin levels (leptin is a positive regulator of hypothalamic PACAP expression in adulthood) of both sexes were decreased by fasting. On the other hand, hypothalamic PAC1 mRNA expression did not change during the neonatal to pre-pubertal period in either sex; however, its levels were consistently higher in males than in females. Hypothalamic PAC1 mRNA expression was decreased by 24h fasting in males, but no such changes were observed in females. These results indicate while hypothalamic PACAP expression is sensitive to a negative energy state and the serum leptin level in adulthood, no such relationships are seen in the pre-pubertal period. In addition, we speculate that differences in the gonadal steroidal milieu might induce sexual dimorphism in the basal hypothalamic PAC1 mRNA level and its response to fasting. The mechanisms responsible for and the physiological effects of such changes in hypothalamic PACAP and PAC1 expression during the developmental period remain to be clarified.

Shorebirds’ Longer Migratory Distances Are Associated With Larger ADCYAP1 Microsatellites and Greater Morphological Complexity of Hippocampal Astrocytes

“…Moreover, PACAP is affected by diet and fasting (Iwasa et al, 2016;Nakata et al, 2016) with important implications for regulation of food intake (Kataoka et al, 2013;Nguyen et al, 2020) and energy homeostasis (Chang et al, 2021) and this seems to include birds (Tachibana et al, 2015;Simon et al, 2017). PACAP is also affected by photoperiodic light changes (Saino et al, 2015;Bazzi et al, 2016a;Adamska et al, 2018;Haraguchi et al, 2019), reproductive conditions (Prisco et al, 2019;Winters and Moore, 2020) and stress (Agarwal et al, 2005;Norrholm et al, 2005;Hammack et al, 2010).…”

The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF

“…Compared to the restraint physical stressor and the other two psychological stressors (elevated platform and predator odor), the MS stressor exhibits more extensive influence on the brain, which is speculated to be associated with the social factor in this stress model. For example, besides the hippocampus and prefrontal cortex, which are susceptible to stress, MS has been reported to affect BDNF expression in the amygdala [27,72], nucleus accumbens [73], VTA [74], striatum [74,75], cerebellum [76], and hypothalamus [77,78] of rodents. In humans, a previous study showed a positive association between serum BDNF levels and maternal overprotection in the Val66Met mutant [79].…”