Adolescent female rats exhibiting activity-based anorexia express elevated levels of GABA(A) receptor α4 and δ subunits at the plasma membrane of hippocampal CA1 spines.
Adolescent female rats exhibiting activity-based anorexia express elevated levels of GABA(A) receptor α4 and δ subunits at the plasma membrane of hippocampal CA1 spines.
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DOI：
10.1002/syn.21528
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发表时间：
2012-05
期刊：
影响因子：
2.3
通讯作者：
Barbarich-Marsteller, Nicole C.
中科院分区：
文献类型：
--
作者：
Aoki, Chiye;Sabaliauskas, Nicole;Chowdhury, Tara;Min, Jung-Yun;Colacino, Anna Rita;Laurino, Kevin;Barbarich-Marsteller, Nicole C.
关键词：
基于活动的厌食症(ABA)是一种神经性厌食症的动物模型，它揭示了遗传与焦虑特征和下丘脑神经化学特征的联系。然而，很少有研究使用这种动物模型来研究青春期和青春期女性对ABA易感性的生物学基础，尽管绝大多数神经性厌食症病例是在青春期表现出首发症状的女性。对海马体的GABA能抑制强烈地调节焦虑和整个生命的可塑性。我们最近发现雌性小鼠的海马CA1在青春期开始时经历了戏剧性的变化-从青春期前几乎不表达非突触的α4βδGABA受体(GABAR)到青春期开始在大约7%的CA1树突棘膜上表达这些GABA受体。此外，我们还发现，这一变化是应激神经类固醇THP(3a-OH-5α[β)-孕酮-20-酮或[allo]孕酮增强焦虑、神经元兴奋性和NMDA受体依赖性突触可塑性的基础。在这里，我们使用定量电子显微镜来确定在青春期诱导雌性大鼠是否也像在小鼠青春期开始时观察到的那样，上调α4和δ亚基α4βδGABA的表达。我们的分析显示，大鼠在青春期开始时也表现出α4和δ亚基的升高，因为在青春期开始(出生后32-36天；P32-36天)，大约6%的αβδ锥体细胞的树突棘膜上可以检测到这些亚基，但到P40-P44时，这一比例下降到约2%。在P40雌鼠暴露于产生ABA所需的两种环境因素中的任何一种时，α4和δ亚单位的水平保持在较低水平。这一模式与ABA动物的模式形成了鲜明的对比，ABA动物的模式是两种环境因素的结合。在ABA动物的海马区，12%的脊柱轮廓被标记为α4，比年龄匹配(P44)的对照组雌性海马区增加了6倍[p<；0.005]。同时，7%的脊柱轮廓被标记为δ，比对照组的3%增加了130%(p=0.0 1)。没有检测到脊柱大小的可测量变化。观察到的脊椎α4和δ亚基的增加幅度足以增加应激期间海马体的紧张性抑制和焦虑，从而可能加剧多动和体重减轻。
Activity-based anorexia (ABA) is an animal model for anorexia nervosa that has revealed genetic links to anxiety traits and neurochemical characteristics within the hypothalamus. However, few studies have used this animal model to investigate the biological basis for vulnerability of pubertal and adolescent females to ABA, even though the great majority of the anorexia nervosa cases are females exhibiting the first symptoms during puberty. GABAergic inhibition of the hippocampus strongly regulates anxiety as well as plasticity throughout life. We recently showed that the hippocampal CA1 of female mice undergo a dramatic change at puberty onset – from expressing virtually none of the non-synaptic α4βδ GABAA receptors (GABARs) pre-pubertally to expressing these GABARs at approximately 7% of the CA1 dendritic spine membranes at puberty onset. Furthermore, we showed that this change underlies the enhanced modulation of anxiety, neuronal excitability and NMDA receptor-dependent synaptic plasticity in the hippocampus by the stress neurosteroid, THP (3a-OH-5α[β]-pregnan-20-one or [allo]pregnanolone). Here, we used quantitative electron microscopy to determine whether ABA induction in female rats during adolescence also elevates the expression of α4 and δ subunits of α4βδ GABARs, as was observed at puberty onset for mice. Our analysis revealed that rats also exhibit a rise of α4 and δ subunits of α4βδ GABARs at puberty onset, in that these subunits are detectable at approximately 6% of the dendritic spine membranes of CA1 pyramidal cells at puberty onset (postnatal day 32–36; P32–36) but this drops to about 2% by P40 – P44. The levels of α4 and δ subunits at the CA1 spines remained low following exposure of P40 females to either of the two environmental factors needed to generate ABA - food restriction and access to a running wheel for four days (P40 to P44). This pattern contrasted greatly from those of ABA animals, for which the two environmental factors were combined. Within the hippocampus of ABA animals, 12% of the spine profiles were labeled for α4, reflecting a six-fold increase, relative to hippocampi of age-matched (P44) control females [p<0.005]. Concurrently, 7% of the spine profiles were labeled for δ, reflecting a 130% increase from the control values of 3% (p=0.01). No measurable change was detected for spine size. The observed magnitude of increase in the α4 and δ subunits at spines is sufficient to increase both tonic inhibition of hippocampus and anxiety during stress, thereby likely to exacerbate hyperactivity and weight loss.
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影响因子：
3.7
作者：
Gutierrez, E.;Churruca, I.;Echevarria, E.
通讯作者：
Echevarria, E.
影响因子：
1.7
作者：
Gutierrez, Emilio;Baysari, Melissa T.;Boakes, Robert A.
通讯作者：
Boakes, Robert A.
影响因子：
5.5
作者：
Birmingham, CL;Su, J;Gao, M
通讯作者：
Gao, M
影响因子：
25
作者：
Essrich, C;Lorez, M;Lüscher, B
通讯作者：
Lüscher, B
DOI：
10.1073/pnas.72.10.4172
发表时间：
1975-01-01
影响因子：
11.1
作者：
FRISCH, RE;HEGSTED, DM;YOSHINAGA, K
通讯作者：
YOSHINAGA, K