背景:慢性含咖啡因(CAFF)饮料的影响的证据,单独或与阿戈美拉汀(AGO)或喹硫平(QUET)合用,脑电图(EEG),这与认知有关,癫痫发生,和卵巢功能,仍然缺乏。雌激素,腺苷碱能,褪黑激素信号可能与这些物质的动力学有关。
目的:比较CAFF与AGO+CAFF和QUET+CAFF对脑和卵巢的影响。雌激素的影响,腺苷碱能,并研究了褪黑激素信号和脑-卵巢串扰。
方法:给成年雌性大鼠服用AGO(10mg/kg),QUET(10mg/kg),CAFF,老+CAFF,或QUET+CAFF,每天一次,共8周。脑电图,发情周期进展,并检查了大脑和卵巢的微观结构。脑和卵巢17β-雌二醇(E2),抗苗勒管激素(AMH),雌激素受体α(E2Rα),腺苷受体2A(A2AR),和褪黑素受体2(MT2R)进行评估。
结果:CAFF,单独或与AGO或QUET结合使用,降低了最大脑电图峰值,与卵巢E2Rα呈正相关,与皮质神经变性和卵巢MT2R呈负相关,与囊性卵巢有关.AGO+CAFF和QUET+CAFF出现大量黄体,拮抗CAFF介导的卵巢A2AR增加和皮质E2Rα减少。AGO+CAFF引起TTP延迟和卵巢AMH增加,而QUETCAFF将源脑电图频率减慢至δ范围,并增加了大脑E2。
结论:CAFF治疗引发的脑和卵巢紊乱与AGO或QUET同时给药部分拮抗,但对发情周期进展没有明显影响。雌激素,腺苷碱能,褪黑激素信号和脑-卵巢串扰可以解释这些影响。
BACKGROUND: Evidence of the effects of chronic caffeine (CAFF)-containing beverages, alone or in combination with agomelatine (AGO) or quetiapine (QUET), on electroencephalography (EEG), which is relevant to cognition, epileptogenesis, and ovarian function, remains lacking. Estrogenic, adenosinergic, and melatonergic signaling is possibly linked to the dynamics of these substances.
OBJECTIVE: The brain and ovarian effects of CAFF were compared with those of AGO + CAFF and QUET + CAFF. The implications of estrogenic, adenosinergic, and melatonergic signaling and the brain-ovarian crosstalk were investigated.
METHODS: Adult female rats were administered AGO (10 mg/kg), QUET (10 mg/kg), CAFF, AGO + CAFF, or QUET + CAFF, once daily for 8 weeks. EEG, estrous cycle progression, and microstructure of the brain and ovaries were examined. Brain and ovarian 17β-estradiol (E2), antimullerian hormone (AMH), estrogen receptor alpha (E2Rα), adenosine receptor 2A (
A2AR), and melatonin receptor 2 (MT2R) were assessed.
RESULTS: CAFF, alone or combined with AGO or QUET, reduced the maximum EEG peak, which was positively linked to ovarian E2Rα, negatively correlated to cortical neurodegeneration and ovarian MT2R, and associated with cystic ovaries. A large corpus luteum emerged with AGO + CAFF and QUET + CAFF, antagonizing the CAFF-mediated increased ovarian
A2AR and reduced cortical E2Rα. AGO + CAFF provoked TTP delay and increased ovarian AMH, while QUET + CAFF slowed source EEG frequency to δ range and increased brain E2.
CONCLUSIONS: CAFF treatment triggered brain and ovarian derangements partially antagonized with concurrent AGO or QUET administration but with no overt affection of estrus cycle progression. Estrogenic, adenosinergic, and melatonergic signaling and brain-ovarian crosstalk may explain these effects.