Sex differences in α-adrenergic receptor function contribute to impaired hypothalamic metaplasticity following chronic intermittent ethanol exposure.
Sex differences in α-adrenergic receptor function contribute to impaired hypothalamic metaplasticity following chronic intermittent ethanol exposure.
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慢性间歇性乙醇暴露后，α-肾上腺素受体功能的性别差异导致下丘脑化生性受损。
DOI：
10.1111/acer.14900
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发表时间：
2022-08
期刊：
影响因子：
--
通讯作者：
Spigelman, Igor
中科院分区：
文献类型：
--
作者：
Munier, Joseph J.;Marty, Vincent N.;Spigelman, Igor
患有酒精使用障碍(AUD)的人表现出下丘脑-垂体-肾上腺(HPA)轴对压力的适应不良反应，这与戒酒期间高复发率有关。促肾上腺皮质激素释放因子(CRF)位于下丘脑室旁核(PVN)内的小细胞神经内分泌细胞(PNC)在应激诱导的HPA轴激活中起关键作用。在这里，我们研究了应激相关神经递质去甲肾上腺素(NE)在AUD大鼠模型中在PNC突触传递和可塑性方面的性别差异。成年SD大鼠暴露于40天的慢性间歇性乙醇(CIE)蒸气和30-60天的长期戒断。我们用全细胞膜片钳记录的方法，观察了去甲肾上腺素(NE，10μM)和选择性α-1肾上腺素能受体(AR)拮抗剂哌唑嗪(10μM)或α-2AR拮抗剂替帕美唑(10μM)作用于PNC和暴露于空气的对照组大鼠脑片的保持电流、诱发突触电流和短期谷氨酸可塑性的变化。NE可引起两种截然不同的效应：去极化的内向突触后电流和诱发的谷氨酸能兴奋性突触后电流(EEPSC)幅度降低。这两种影响都是性别和CIE特有的。哌唑嗪阻断突触后内向电流，而阿替帕唑阻断NE对eEPSCs的抑制作用。此外，只有在压力幼稚的雄性动物施加NE后，STP的形成才被促进，而在CIE暴露后暴露于30分钟束缚应激的应激动物中，这种反应消失了。此外，NE+哌唑嗪可恢复应激CIE雄性大鼠STP的形成。NE对CRF、PVN、PNC均有兴奋和抑制作用，且这两种作用均受性别和CIE的影响。对应激的行为和激素反应受PVN内STP形成的影响，这种反应在CIE后消失，并在预先应用哌唑嗪后恢复。因此，选择性阻断α1AR可能以一种性别特异性的方式改善CIE诱导的HPA应激反应缺陷。
Individuals afflicted with alcohol use disorder (AUD) exhibit maladaptive responses of the hypothalamic-pituitary-adrenal (HPA) axis to stress, which has been linked to high relapse rates to drinking during abstinence. Corticotropin-releasing factor (CRF) parvocellular neuroendocrine cells (PNCs) within the paraventricular nucleus of the hypothalamus (PVN) are critical to stress-induced HPA axis activation. Here, we investigate sex differences in synaptic transmission and plasticity in PNCs following application of stress-associated neurotransmitter, norepinephrine (NE) in a rat model of AUD. Adult Sprague-Dawley rats were exposed to 40 days of chronic intermittent ethanol (CIE) vapor and 30–60 days of protracted withdrawal. We measured changes in holding current, evoked synaptic currents, and short-term glutamatergic plasticity (STP) in putative PNCs following NE (10 μM) application with and without selective α1 adrenergic receptor (AR) antagonist, prazosin (10μM) or α2AR antagonist, atipamezole (10μM), using whole-cell patch clamp recordings in slices from CIE rats and air-exposed controls. NE application caused two distinct effects: a depolarizing, inward, postsynaptic current and a reduction in evoked glutamatergic excitatory postsynaptic current (eEPSC) amplitude. Both effects were sex and CIE-specific. Prazosin blocked the postsynaptic inward current, while atipamezole blocked the NE-mediated suppression of eEPSCs. Additionally, STP formation was facilitated following NE application in only stress-naïve males and this response was lost in stressed animals exposed to a 30-minute restraint stress following CIE exposure. Furthermore, NE + prazosin restored STP formation in stressed CIE males. NE exerts excitatory and inhibitory effects onto CRF PVN PNCs and both effects are influenced by sex and CIE. Behavioral and hormonal responses to stress are influenced by STP formation within the PVN, which is lost following CIE and restored with pre-application of prazosin. Selective blockade of α1AR may therefore ameliorate CIE-induced deficits in HPA responses to stress in a sex-specific manner.
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影响因子：
6.2
作者：
Gaidin, Sergei G.;Zinchenko, Valery P.;Kosenkov, Artem M.
通讯作者：
Kosenkov, Artem M.
影响因子：
3.4
作者：
Nielsen CK;Simms JA;Bito-Onon JJ;Li R;Ananthan S;Bartlett SE
通讯作者：
Bartlett SE
影响因子：
3.6
作者：
Getachew, Bruk;Hauser, Sheketha R.;Tizabi, Yousef
通讯作者：
Tizabi, Yousef
DOI：
10.1111/acer.13434
发表时间：
2017-08
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Kimbrough A;Kim S;Cole M;Brennan M;George O
通讯作者：
George O
影响因子：
25
作者：
Daviu, Nuria;Fuzesi, Tamas;Bains, Jaideep S.
通讯作者：
Bains, Jaideep S.