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孕激素和别孕烯醇酮对雌性大鼠认知功能和海马基底(放射层)树突棘的周期性变化和作用。

Cyclic changes and actions of progesterone and allopregnanolone on cognition and hippocampal basal (stratum oriens) dendritic spines of female rats.

机构信息

Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico.

Facultad de Medicina, Universidad Autónoma de México, Mexico.

出版信息

Behav Brain Res. 2020 Feb 3;379:112355. doi: 10.1016/j.bbr.2019.112355. Epub 2019 Nov 12.

DOI:10.1016/j.bbr.2019.112355
PMID:31730784
Abstract

Ovarian steroids modulate the neuronal structure and function during the estrous cycle, contrasting peak effects during the proestrus cycle and low effects during the metestrus cycle. An ovariectomy (OVX) decreases gonadal hormones and tests the effects of substitutive therapies. We studied female rats with a normal estrous cycle and we also studied the effects of systemic progesterone (P4, 4.0 mg/kg) or its reduced metabolite allopregnanolone (ALLO, 4.0 mg/kg, both for 10 days) in females who had had an OVX 16.5 weeks prior to the study (long-term OVX) with the novel object recognition test (NORT) for associative memory. The dendritic shape and spine density in Golgi-impregnated basal dendrites (stratum oriens) of hippocampal pyramidal neurons was also studied. Proestrus females had a better performance than metestrus or OVX females in short-term memory (tested 1 h after the acquisition phase). Proestrus and metestrus females showed better results than OVX females for long-term memory (24 h after the initial phase). Both P4 and ALLO recovered the cognitive impairment induced by long-term OVX. Also, proestrus females had a higher density of dendritic spines than metestrus females, OVX reduced the density of spines when compared to intact females, whereas both P4 and ALLO treatments increased the dendritic spine density, number of dendritic branches along the dendritic length, and branching order compared to vehicle. These data add the dendrites of the stratum oriens as an additional site for naturally occurring changes in spine density during the estrous cycle and evidence the actions of progestins in both behavioral recovery and the structural dendritic rearrangement of hippocampal pyramidal neurons in long-term OVX female rats.

摘要

卵巢类固醇在动情周期中调节神经元的结构和功能,在发情前期周期中呈现高峰效应,而在动情中期周期中呈现低效应。卵巢切除术(OVX)会降低性腺激素,并测试替代疗法的效果。我们研究了具有正常动情周期的雌性大鼠,还研究了全身性孕酮(P4,4.0mg/kg)或其还原代谢产物孕烷醇酮(ALLO,4.0mg/kg,均持续 10 天)对研究前 16.5 周进行 OVX 的雌性大鼠的影响,使用新颖物体识别测试(NORT)进行联想记忆测试。还研究了海马锥体神经元的高尔基浸渍基底树突(放射层)中的树突形状和棘突密度。在短期记忆(获得阶段后 1 小时测试)中,发情前期雌性的表现优于发情中期或 OVX 雌性。在长期记忆(初始阶段后 24 小时)中,发情前期和发情中期雌性的表现优于 OVX 雌性。P4 和 ALLO 均恢复了长期 OVX 引起的认知障碍。此外,发情前期雌性的树突棘密度高于发情中期雌性,OVX 与完整雌性相比降低了棘突密度,而 P4 和 ALLO 处理均增加了树突棘密度、沿树突长度的树突分支数量和分支顺序与载体相比。这些数据将放射层的树突添加为在动情周期中自然发生的棘突密度变化的另一个部位,并证明孕激素在长期 OVX 雌性大鼠的行为恢复和海马锥体神经元的结构树突重排中均具有作用。

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