Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.
Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.
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DOI：
10.1111/ejn.13870
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Donaldson ST
中科院分区：
文献类型：
--
作者：
Ravenelle R;Berman AK;La J;Mason B;Asumadu E;Yelleswarapu C;Donaldson ST
在人类和动物模型中，报告了焦虑样行为和对焦虑刺激的反应的性别差异。在当前的工作中，我们研究了焦虑样行为和对典型抗焦虑药物地西泮的反应。我们使用具有高和低焦虑样行为表型的成年Long Evans大鼠的第6代远交系来研究发情前期对基线和地西泮诱导的行为的影响。在三个剂量的地西泮（0、0.1和1.0 mg/kg，i. p.）下，我们测量了成年雄性和雌性大鼠在高架十字迷宫上的焦虑反应。我们使用免疫组织化学评估了与焦虑/压力有关的前脑和边缘结构中的小清蛋白和脑源性神经营养因子蛋白水平。在基线时，我们看到焦虑线之间存在显著差异，高焦虑线显示高架十字迷宫开放臂上的时间更少，开放臂条目更少，无论性别如何。在发情前期，与雄性动物相比，0.1 mg/kg剂量组高焦虑雌性动物的焦虑样行为较少，而0.1和1.0剂量组低焦虑雌性动物的焦虑样行为较少。脑源性神经营养蛋白升高，女性在内侧前额叶皮层和中央杏仁核，而小白蛋白免疫反应阳性细胞在男性内侧前额叶皮层。高焦虑女性的小白蛋白阳性细胞在CA 2和齿状回相对于来自同一行的男性更高。总之，当在发情前期进行测试时，雌性动物表现出比雄性动物更强的地西泮抗焦虑作用，这与皮质边缘结构中神经营养因子和小清蛋白神经元密度增加相关。使用表型为显示高（HAn）和低焦虑（LAn）样行为的动物的远交系，我们证实了HAn F6后代在基线时在高架十字迷宫（高架十字迷宫）的开放臂上不太活跃。在地西泮治疗后，HAn和LAn雌性动物在张开的双臂上更活跃。使用图形用户间期，我们计数了更多的阳性染色的小清蛋白神经元（即，染色GABA神经元的子集）。
In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1 and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. Using outbred lines of animals phenotyped as showing high (HAn) and low anxiety (LAn)-like behavior, we confirmed HAn F6 offspring were less active on the open arms of the elevated plus maze (EPM) at baseline. HAn and LAn females were more active on the open arms of the EPM after diazepam treatment. Using a graphic user interphase, we counted a greater number of positively stained parvalbumin neurons (i.e., that stain a subset of GABA neurons) in CA2 and DG of the hippocampus.
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影响因子：
10.6
作者：
Bath, Kevin G.;Chuang, Jocelyn;Spencer-Segal, Joanna L.;Amso, Dima;Altemus, Margaret;McEwen, Bruce S.;Lee, Francis S.
通讯作者：
Lee, Francis S.
影响因子：
1.6
作者：
Kelly TH;Delzer TA;Martin CA;Harrington NG;Hays LR;Bardo MT
通讯作者：
Bardo MT
影响因子：
3.5
作者：
Lofgren, Magnus;Johansson, Inga-Maj;Backstrom, Torbjorn
通讯作者：
Backstrom, Torbjorn
影响因子：
5.3
作者：
Earnheart, John C.;Schweizer, Claude;Luscher, Bernhard
通讯作者：
Luscher, Bernhard
影响因子：
1.9
作者：
BITRAN, D;HILVERS, RJ;KELLOGG, CK
通讯作者：
KELLOGG, CK