Gregorio Tamires, Lorenzon Flaviano, Niebisch Fernanda, Stolte Rafaela Carla Kachel, Rafacho Alex, Dos Santos Gustavo Jorge, Lino de Oliveira Cilene, Lima Fernanda Barbosa
Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus, Florianópolis, SC, Brazil.
Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil.
Physiol Behav. 2022 May 15;249:113765. doi: 10.1016/j.physbeh.2022.113765. Epub 2022 Feb 26.
Overexposure to glucocorticoids during gestation can lead to long-term mental disorders. Given the higher prevalence of depression in females, we investigated whether late gestational administration of dexamethasone could generate a depressive-like phenotype in the adult female offspring and if vitamin D could have a neuroprotective effect in this context. Pregnant rats received vitamin D (VitD, 500 IU/day) or vehicle (CTL) during gestation. Other pregnant rats received dexamethasone (Dex 0.1 mg/kg/ - 14th to the 19th gestational day) or dexamethasone + vitamin D (DexVitD). The offspring were tested for anhedonia (sucrose preference) and depressive-like behavior (forced swimming test) at postnatal months (PNM) 3, 6 and 12. Components of the serotonergic system, as well as glucocorticoids' receptors, were evaluated in the dorsal raphe nucleus at PNM 6 and 12. Prenatal vitamin D and dexamethasone increased sucrose preference at PNM 12. Prenatal vitamin D had an antidepressant-like effect at PNM 3 in rats overexposed to dexamethasone. However, at PNM 12, this effect was blunted in the DexVitD group. Prenatal dexamethasone reduced the protein content of SERT, TPH, and 5-HT receptors in the dorsal raphe nucleus at 6 but not at 12 PNM. The glucocorticoids' receptors expression was similar in all groups. We concluded that prenatal overexposure to dexamethasone does not change emotional behaviors in females, but it blunts the antidepressant-like effect of gestational vitamin D in an age-dependent manner. The antidepressant-like activity of vitamin D in the offspring was not related either to alterations of the serotonergic system or the glucocorticoids' receptors expression in the dorsal raphe nucleus.
孕期糖皮质激素暴露过量可导致长期精神障碍。鉴于女性抑郁症患病率较高，我们研究了妊娠晚期给予地塞米松是否会在成年雌性后代中产生类似抑郁的表型，以及维生素D在此情况下是否具有神经保护作用。妊娠大鼠在孕期接受维生素D（VitD，500 IU/天）或赋形剂（CTL）。其他妊娠大鼠接受地塞米松（Dex，0.1 mg/kg，从妊娠第14天至第19天）或地塞米松+维生素D（DexVitD）。在出生后3、6和12个月对后代进行快感缺失（蔗糖偏好）和类似抑郁行为（强迫游泳试验）测试。在出生后6个月和12个月评估中缝背核中血清素能系统的组成部分以及糖皮质激素受体。产前维生素D和地塞米松增加了出生后12个月时的蔗糖偏好。产前维生素D对过度暴露于地塞米松的大鼠在出生后3个月时有类似抗抑郁的作用。然而，在出生后12个月时，DexVitD组的这种作用减弱。产前地塞米松在出生后6个月时降低了中缝背核中SERT、TPH和5-HT受体的蛋白质含量，但在出生后12个月时没有降低。所有组中糖皮质激素受体的表达相似。我们得出结论，产前过度暴露于地塞米松不会改变雌性的情绪行为，但会以年龄依赖的方式减弱孕期维生素D的类似抗抑郁作用。后代中维生素D的类似抗抑郁活性与中缝背核中血清素能系统的改变或糖皮质激素受体的表达均无关。
