a Universidade Federal de Pernambuco , Cidade Universitaria , Brazil.
Nutr Neurosci. 2019 Mar;22(3):174-184. doi: 10.1080/1028415X.2017.1358472. Epub 2017 Sep 10.
Ovarian hormones (OH) and early malnutrition may affect the developing brain, with repercussions on behavioral and excitability-dependent processes. However, the possible synergistic effects of both factors have not been analyzed. In this study, we investigated the effect of treatment in early life with OH and suckling among distinct litter sizes on recognition memory, anxiety behavior, and the excitability-dependent phenomenon known as cortical spreading depression (CSD).
Female Wistar rats were suckled under favorable and unfavorable lactation, corresponding to litters with 9 and 15 pups (L and L groups, respectively). From postnatal days (P) 7 to 21, the animals received 50 µg/kg of β-estradiol or progesterone. From P80 to P84, we tested behavioral reactions. From P90 to P120, we analyzed CSD parameters.
Compared with the corresponding L groups, the OH-treated L groups performed worse in recognition memory tasks. No intergroup difference in the anxiety parameters was observed. Compared with naive and vehicle-treated controls, OH-treated groups displayed higher CSD velocities and amplitudes and shorter CSD durations.
Early treatment with OH facilitates recognition memory and CSD, and in association with unfavorable lactation (L) impaired recognition memory, but not anxiety behavior, in the adult brain. OH treatment and L lactation condition seem to interact regarding OH action on memory, but not on CSD. Data suggest a long-lasting differential effect that might be related to the lasting hormonal action on brain excitability. We postulate and discuss the possibility that these findings may be implicated in human neurological diseases.
卵巢激素(OH)和早期营养不良可能会影响大脑发育,对行为和兴奋性相关过程产生影响。然而,这两个因素的协同作用尚未得到分析。在这项研究中,我们研究了在不同窝仔数的早期生活中用 OH 和哺乳进行治疗对识别记忆、焦虑行为以及称为皮质扩散性抑制(CSD)的兴奋性依赖性现象的影响。
雌性 Wistar 大鼠在有利和不利的哺乳期下哺乳,对应于 9 只和 15 只幼崽的窝仔数(L 和 L 组,分别)。从出生后第 7 天到第 21 天,动物接受 50µg/kg 的β-雌二醇或孕酮。从第 80 天到第 84 天,我们测试了行为反应。从第 90 天到第 120 天,我们分析了 CSD 参数。
与相应的 L 组相比,OH 治疗的 L 组在识别记忆任务中表现较差。在焦虑参数方面没有观察到组间差异。与未处理的和载体处理的对照组相比,OH 处理组的 CSD 速度和幅度更高,CSD 持续时间更短。
早期用 OH 治疗可促进识别记忆和 CSD,并且与不利的哺乳(L)相结合,损害了成年大脑的识别记忆,但不损害焦虑行为。OH 治疗和 L 哺乳条件似乎在 OH 对记忆的作用方面相互作用,但在 CSD 方面没有。数据表明存在长期的差异效应,这可能与激素对大脑兴奋性的持久作用有关。我们假设并讨论了这些发现可能与人类神经疾病有关的可能性。