Neuropharmacology最新文献_第9页

Leveling up: Strategies for taking Neuropharmacology and us all to new heights 升级：将神经药理学和我们所有人带到新高度的策略。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-06 DOI: 10.1016/j.neuropharm.2025.110297

Jared W. Young Ph.D

引用次数: 0

Cholesterol metabolites modulate ionotropic P2X4 and P2X7 receptor current in microglia cells 胆固醇代谢物调节小胶质细胞中P2X4和P2X7受体电流。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-02 DOI: 10.1016/j.neuropharm.2024.110294

Michele Barraco , Eva Kudova , Claudio Bucolo , Lucia Ciranna , Maria Angela Sortino , Mariangela Chisari

The central nervous system is a well-known steroidogenic tissue producing, among others, cholesterol metabolites such as neuroactive steroids, oxysterols and steroid hormones. It is well known that these endogenous molecules affect several receptor classes, including ionotropic GABAergic and NMDA glutamatergic receptors in neurons. It has been shown that also ionotropic purinergic (P2X) receptors are cholesterol metabolites’ targets. Among P2X receptors, purinergic P2X4 and P2X7 receptors are expressed in microglia, the innate immune cells involved in the brain inflammatory response. In this study, we explore the ionotropic purinergic receptors modulation by cholesterol metabolites in microglia. Patch-clamp experiments were performed in BV2 cells, a murine microglia cell line, to evaluate effects of cholesterol metabolites using micro- and nanomolar concentrations. About P2X4 receptor, we found that testosterone butyrate (20 μM and 200 nM) and allopregnanolone (10 μM and 100 nM) both potentiated its current, while neither 25-hydroxycholesterol (10 μM and 100 nM) nor 17β-estradiol (1 μM) showed any effects. On the other hand, P2X7 receptor current was potentiated by allopregnanolone (10 μM) and 25-hydroxycholesterol (10 μM and 100 nM). Taken together, our data show that modulation of either P2X4 and P2X7 current is affected differently by cholesterol metabolites, suggesting a structure-activity relationship among these players. Identifying the possible link between purinergic transmission, microglia and cholesterol metabolites will allow to define new targets for drug development to treat neuroinflammation.

中枢神经系统是众所周知的类固醇生成组织，产生胆固醇代谢产物，如神经活性类固醇、羟甾醇和类固醇激素。众所周知，这些内源性分子影响几种受体，包括神经元中的嗜离子性gaba能受体和NMDA谷氨酸能受体。研究表明，嗜离子嘌呤能（P2X）受体也是胆固醇代谢产物的靶点。在P2X受体中，嘌呤能P2X4和P2X7受体在参与脑炎症反应的先天免疫细胞小胶质细胞中表达。在本研究中，我们探讨了小胶质细胞中胆固醇代谢产物对嗜离子嘌呤能受体的调节。膜片钳实验在小鼠小胶质细胞BV2细胞中进行，以评估微摩尔浓度和纳摩尔浓度对胆固醇代谢物的影响。对于P2X4受体，我们发现丁酸睾酮（20 μM和200 nM）和异孕酮（10 μM和100 nM）均能增强其电流，而25-羟基胆固醇（10 μM和100 nM）和17β-雌二醇（1 μM）对其电流没有影响。另一方面，异孕酮（10 μM）和25-羟基胆固醇（10 μM和100 nM）可增强P2X7受体电流。综上所述，我们的数据显示P2X4和P2X7电流的调节受到胆固醇代谢物的不同影响，表明这些参与者之间存在结构-活性关系。确定嘌呤能传递、小胶质细胞和胆固醇代谢物之间的可能联系，将有助于确定治疗神经炎症的药物开发的新目标。

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引用次数: 0

Microglial activation and neuroinflammation in acute and chronic cognitive deficits in sepsis 脓毒症患者急性和慢性认知缺陷中的小胶质细胞激活和神经炎症。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2024-12-31 DOI: 10.1016/j.neuropharm.2024.110285

Paul Denver , Colm Cunningham

Sepsis is characterised by dysregulated immune responses to infection, leading to multi-organ dysfunction and high rates of mortality. With increasing survival rates in recent years long-term neurological and psychiatric consequences have become more apparent in survivors. Many patients develop sepsis associated encephalopathy (SAE) which encompasses the profound but usually transient neuropsychiatric syndrome delirium but also new brain injury that emerges in the months and years post-sepsis. It is now clear that systemic inflammatory signals reach the brain during sepsis and that very significant neuroinflammation ensues. The major brain resident immune cell population, the microglia, has been implicated in acute and chronic cognitive dysfunction in animal models of sepsis based on a growing number of studies using bacterial endotoxin and in polymicrobial sepsis models such as cecal ligation and puncture. The current review explores the effects of sepsis on the brain, focussing on how systemic insults translate to microglial activation and neuroinflammation and how this disrupts neuronal function and integrity. We examine what has been demonstrated specifically with respect to microglial activation, revealing robust evidence for a role for neuroinflammation in sepsis-induced brain sequelae but less clear information on the extent of the specific microglial contribution to this, arising from findings using global knockout mice, non-selective drugs and treatments that equally target peripheral and central compartments. There is, nonetheless, clear evidence that microglia do become activated and do contribute to brain consequences of sepsis thus arguing for improved understanding of these neuroinflammatory processes toward the prevention and treatment of sepsis-induced brain dysfunction.

脓毒症的特点是对感染的免疫反应失调，导致多器官功能障碍和高死亡率。随着近年来生存率的提高，长期的神经和精神后果在幸存者中变得更加明显。许多患者出现脓毒症相关脑病（SAE），包括严重但通常是短暂的神经精神综合征谵妄，但也有新的脑损伤出现在脓毒症后的几个月和几年。现在很清楚，在败血症期间，全身炎症信号到达大脑，随之而来的是非常严重的神经炎症。基于越来越多的使用细菌内毒素和多微生物脓毒症模型（如盲肠结扎和穿刺）的研究，主要的脑免疫细胞群小胶质细胞与脓毒症动物模型中的急性和慢性认知功能障碍有关。目前的综述探讨了败血症对大脑的影响，重点关注系统性损伤如何转化为小胶质细胞激活和神经炎症，以及这如何破坏神经元功能和完整性。我们研究了关于小胶质细胞激活的具体证明，揭示了神经炎症在败血症诱导的脑后遗症中的作用的有力证据，但关于特定小胶质细胞对此的贡献程度的不明确信息，这些信息来自使用全局敲除小鼠、非选择性药物和同样针对外周和中央室的治疗的发现。尽管如此，有明确的证据表明，小胶质细胞确实被激活，并且确实有助于败血症的脑后果，因此，为了预防和治疗败血症引起的脑功能障碍，需要改进对这些神经炎症过程的理解。

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引用次数: 0

A term as Editor-in-Chief of Neuropharmacology: Ups and downs and highs and lows 作为《神经药理学》主编的一个术语：起起落落，起起伏伏。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2024-12-30 DOI: 10.1016/j.neuropharm.2024.110270

Bruno G. Frenguelli

引用次数: 0

Thank you to our reviewers

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2024-12-30 DOI: 10.1016/j.neuropharm.2024.110274

引用次数: 0

Clozapine and rapamycin reverse behavioral abnormalities in an animal model of autoimmune schizophrenia 氯氮平和雷帕霉素逆转自身免疫性精神分裂症动物模型中的行为异常

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2024-12-27 DOI: 10.1016/j.neuropharm.2024.110286

Duilin Liu , Caiyun Zhu , Hui Wei

Objective

Autoantibody-associated psychosis represents a distinct disease subgroup of patients with schizophrenia with a suspected autoimmune origin. Although preliminary studies have suggested adjunctive drug treatment strategies targeting the immune system, further validation of these findings is warranted. Autoantibodies against SFT2D2 have been identified in patients with schizophrenia. ApoE^−/− mice immunized with SFT2D2-peptides can be used as a model for testing immunotherapy in this subgroup of patients. We used the atypical antipsychotic drug clozapine and immunosuppressant rapamycin to test their effects in this mouse model.

Methods

The mice were evaluated for cognitive and schizophrenia-like behaviors. Following behavioral testing, brain samples were collected for analyzing specific pathological changes and dendritic spine formation.

Results

Clozapine and rapamycin reversed impaired pre-pulse inhibition, motor impairment, and improved cognitive ability in ApoE ^−/− mice exposed to anti-SFT2D2 immunoglobulin G. Immunohistochemical assays revealed that both clozapine and rapamycin significantly reduced activated microglial infiltration and restored neuronal dendritic spine density.

Conclusions

Our study results suggested that clozapine and rapamycin possess therapeutic benefits for managing autoimmune psychosis and provide mechanistic insights into immunotherapies involving immunosuppressive agents.

目的：自身抗体相关精神病是精神分裂症患者的一个独特的疾病亚组，疑似自身免疫性起源。虽然初步研究已经提出了针对免疫系统的辅助药物治疗策略，但需要进一步验证这些发现。在精神分裂症患者中发现了针对SFT2D2的自身抗体。用sft2d2肽免疫的ApoE-/-小鼠可以作为测试该亚组患者免疫治疗的模型。我们使用非典型抗精神病药物氯氮平和免疫抑制剂雷帕霉素在小鼠模型中测试它们的作用。方法：对小鼠的认知行为和精神分裂症样行为进行评估。行为测试后，采集脑样本分析具体病理变化和树突棘形成情况。结果：氯氮平和雷帕霉素逆转了暴露于抗sft2d2免疫球蛋白g的ApoE -/-小鼠的脉冲前抑制受损、运动障碍和认知能力改善。免疫组化分析显示，氯氮平和雷帕霉素均显著减少了活化的小胶质细胞浸润，恢复了神经元树突棘密度。结论：我们的研究结果表明氯氮平和雷帕霉素在治疗自身免疫性精神病方面具有治疗效果，并为免疫抑制剂的免疫治疗提供了机制见解。

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引用次数: 0

Angiotensin 1-7 injected into the rat paraventricular nucleus of hypothalamus increases blood pressure and heart rate via various receptors 大鼠下丘脑室旁核注射血管紧张素1-7，可通过多种受体提高血压和心率。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2024-12-26 DOI: 10.1016/j.neuropharm.2024.110279

K. Mińczuk , E. Schlicker , A. Krzyżewska , B. Malinowska

Although angiotensin 1-7 (Ang 1–7) and its role as a part of the “protective” axis of the renin-angiotensin system are well described in the literature, the mechanisms of its angiotensin II-like pressor and tachycardic effects following its acute central administration are not fully understood. It was the aim of the present study to examine which receptors contribute to the aforementioned cardiovascular effects. Ang 1–7 and antagonists for glutamate, GABA, vasopressin, thromboxane A₂ (TP), α₁-adrenergic, and P2X purinoceptors or modulators of oxidative stress were injected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anesthetized male Wistar rats. Acute injection of Ang 1–7 into the PVN increased blood pressure (BP) by about 15 mmHg and heart rate (HR) by about 14 beats/min. After preinjection with bicuculline (GABA_A receptor antagonist), CNQX + D-AP5 (AMPA/kainate and NMDA receptor antagonists) and SQ29548 (TP receptor antagonist) the BP and HR reactions to Ang 1–7 were attenuated or abolished. The vasopressin V_1A and V_1B receptor antagonists conivaptan and nelivaptan, and the NADPH oxidase inhibitor apocynin even reversed the pressor and tachycardic effects of Ang 1–7. Antagonists of P2X (PPADS) and α₁-adrenergic receptors (prazosin), the free radical scavenger tempol and the superoxide dismutase inhibitor DETC did not modify the cardiovascular effects of Ang 1–7. The (Mas receptor-related) rise in BP and HR evoked by Ang 1-7 administered to the rat PVN is linked to glutamate, vasopressin, GABA_A and thromboxane receptors, and to oxidative stress, but does not seem to involve α₁-adrenergic or P2X receptors.

尽管血管紧张素1-7 （Ang 1-7）及其作为肾素-血管紧张素系统“保护”轴的一部分的作用在文献中得到了很好的描述，但其血管紧张素ii样加压和急性中枢给药后的心动过速作用的机制尚未完全了解。本研究的目的是检查哪些受体有助于上述心血管效应。将Ang 1-7和谷氨酸、GABA、血管加压素、血栓素A2 （TP）、α1-肾上腺素能和P2X嘌呤受体拮抗剂或氧化应激调节剂注射到聚氨酯麻醉的雄性Wistar大鼠下丘脑室旁核（PVN）。急性向PVN注射Ang 1-7使血压（BP）升高约15 mmHg，心率（HR）升高约14次/分。预注射双库兰（GABAA受体拮抗剂）、CNQX + D-AP5 （AMPA/kainate和NMDA受体拮抗剂）和SQ29548 （TP受体拮抗剂）后，Ang 1-7的BP和HR反应减弱或消失。抗利尿激素V1A和V1B受体拮抗剂康伐他坦和奈利伐他坦，以及NADPH氧化酶抑制剂罗布宁甚至逆转了Ang 1-7的升压和心动过速作用。P2X （PPADS）和α1-肾上腺素能受体（prazosin）的拮抗剂、自由基清除剂tempol和超氧化物歧化酶抑制剂DETC没有改变Ang 1-7的心血管作用。给药大鼠PVN的Ang 1-7引起的（Mas受体相关的）血压和心率升高与谷氨酸、加压素、GABAA和血栓素受体以及氧化应激有关，但似乎与α1-肾上腺素能或P2X受体无关。

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引用次数: 0

Curcumin analog C16 attenuates bone cancer pain induced by MADB 106 breast cancer cells in female rats and inhibits the CREB/NLGN2 signaling axis by targeting CaMKⅠα 姜黄素类似物C16通过靶向CaMKⅠα抑制CREB/NLGN2信号轴，减轻雌性大鼠MADB 106乳腺癌细胞诱导的骨癌疼痛。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2024-12-25 DOI: 10.1016/j.neuropharm.2024.110284

Liping Chen , Chaobo Ni , Dashan Lu , Shuyao Zhang , Yuhua Li , Dongjie Wang , Bohan Hua , Huadong Ni , Longsheng Xu , Ming Yao

Bone cancer pain (BCP) is one of the most severe complications faced by patients with cancer; however, current pharmacological options are limited. Curcumin has been demonstrated to possess anti-inflammatory and analgesic properties; however, our preliminary research found that the analgesic efficiency of curcumin is not high in BCP. Consequently, curcumin analogs have emerged as a significant focus of our research. This study aimed to systematically investigate the analgesic effects of C16 in rats with BCP induced by MADB 106 breast cancer cells (MADB 106-induced BCP) and elucidate the underlying molecular mechanisms. A range of experimental methods, including kinase profiling, transcriptome sequencing, behavioral tests, immunofluorescence, and biochemical analyses, were employed to comprehensively assess the role of C16 in the MADB 106-induced BCP model. The results indicated that C16 significantly alleviated bone cancer pain induced by Luciferin-MADB 106 cells (10ˆ6 cells) in a dose-dependent manner. Importantly, kinase profiling and validation experiments identified CaMKIα in spinal dorsal horn neurons as the primary target of C16's analgesic effect on MADB 106-induced BCP. Continuous intrathecal administration of C16 markedly suppressed the expression of CREB and P-CREB and reduced the expression of neuroligin 2 in the spinal cords of BCP rats, thereby clarifying the mechanism of action of C16 in alleviating MADB 106-induced BCP. These findings suggest that C16 possesses significant therapeutic potential for mitigating MADB 106-induced BCP nociceptive hypersensitivity, providing a foundation for the future development of novel drugs targeting MADB 106-induced BCP.

This article is part of the Special Issue on "Empathic Pain".

骨癌疼痛是癌症患者面临的最严重的并发症之一；然而，目前的药物选择是有限的。姜黄素已被证明具有抗炎和镇痛的特性；然而，我们的初步研究发现，姜黄素在BCP中的镇痛作用并不高。因此，姜黄素类似物已成为我们研究的一个重要焦点。本研究旨在系统探讨C16对MADB 106乳腺癌细胞诱导的BCP （MADB 106诱导的BCP）大鼠的镇痛作用，并阐明其分子机制。采用一系列实验方法，包括激酶谱分析、转录组测序、行为测试、免疫荧光和生化分析，全面评估C16在MADB 106诱导的BCP模型中的作用。结果表明，C16显著缓解Luciferin-MADB 106细胞（10 - 6细胞）诱导的骨癌疼痛，且呈剂量依赖性。重要的是，激酶谱分析和验证实验发现，脊髓背角神经元中的CaMKIα是C16对MADB 106诱导的BCP镇痛作用的主要靶点。持续鞘内给药C16可显著抑制BCP大鼠脊髓中CREB和P-CREB的表达，降低神经素2的表达，从而阐明C16缓解madb106诱导的BCP的作用机制。上述结果提示，C16在缓解MADB 106诱导的BCP伤害性超敏反应方面具有显著的治疗潜力，为未来开发针对MADB 106诱导的BCP的新药奠定了基础。

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引用次数: 0

Inosine exerts dopaminergic neuroprotective effects via mitigation of NLRP3 inflammasome activation 肌苷通过减轻NLRP3炎性体激活发挥多巴胺能神经保护作用。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2024-12-24 DOI: 10.1016/j.neuropharm.2024.110278

Shristi Khanal , Eun-Joo Shin , Chang Jae Yoo , Jaekwang Kim , Dong-Young Choi

Neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Transformation of pro-interleukin (IL)-1β into a mature IL-1β via active inflammasome may be related to the progression of PD. Therefore, the modification of inflammasome activity may be a potential therapeutic strategy for PD. Inosine has been shown to exert anti-inflammatory effects in various disease models. In this study, we evaluated inosine's inhibitory effects on the microglial NLRP3 inflammasome, which may be related to the dopaminergic neuroprotective effects of inosine. Inosine suppresses lipopolysaccharides (LPS)-induced NLRP3 inflammasome activation in BV-2 microglial cells dose dependently. When SH-SY5Y cells were treated with conditioned medium from BV-2 cells treated with LPS and inosine, an NLRP3 inhibitor, or a caspase-1 inhibitor, the viability of SH-SY5Y cells was reduced indicating that LPS-induced microglial inflammasome activation could contribute to neuronal death. Inosine's modulatory effect on NLRP3 inflammasome activity appears to rely on the adenosine A_2A and A₃ receptors activation, as A_2A or A₃ receptor antagonists reversed the amelioration of NLRP3 activation by inosine. In addition, inosine treatment attenuated intracellular and mitochondrial ROS production mediated by LPS and this effect might be related to attenuation of NLRP3 inflammasome activity, as the antioxidant, N-acetyl cysteine ameliorated LPS-induced activation of the inflammasome. Finally, we assessed the inosine's neuroprotective effects via inflammasome activity modulation in mice receiving an intranigral injection of LPS. Immunohistochemical analysis revealed that LPS caused a significant loss of nigral dopaminergic neurons, which was mitigated by inosine treatment. LPS increased NLRP3 expression in IBA1-positive microglial cells, which was attenuated by inosine injection. These findings indicate that inosine can rescue neurons from LPS-induced injury by ameliorating NLRP3 inflammasome activity. Therefore, inosine could be applied as an intervention for neuroinflammatory diseases such as Parkinson's disease.

神经炎症在帕金森病（PD）的发病机制中起着至关重要的作用。白细胞介素(IL)-1β通过活性炎性体转化为成熟的IL-1β可能与PD的进展有关。因此，炎性体活性的改变可能是帕金森病的一种潜在治疗策略。肌苷已被证明在各种疾病模型中发挥抗炎作用。在本研究中，我们评估了肌苷对小胶质NLRP3炎性体的抑制作用，这可能与肌苷的多巴胺能神经保护作用有关。肌苷抑制脂多糖（LPS）诱导的BV-2小胶质细胞NLRP3炎性体激活的剂量依赖性。当SH-SY5Y细胞用LPS和肌苷（一种NLRP3抑制剂或caspase-1抑制剂）处理的BV-2细胞的条件培养基处理时，SH-SY5Y细胞的活力降低，这表明LPS诱导的小胶质炎性体活化可能导致神经元死亡。肌苷对NLRP3炎性体活性的调节作用似乎依赖于腺苷A2A和A3受体的激活，因为A2A或A3受体拮抗剂逆转了肌苷对NLRP3激活的改善。此外，肌苷处理减弱了LPS介导的细胞内和线粒体ROS的产生，这种作用可能与NLRP3炎症小体活性的减弱有关，因为抗氧化剂n -乙酰半胱氨酸改善了LPS诱导的炎症小体活化。最后，我们评估了肌苷的神经保护作用，通过炎症小体活性调节小鼠接受黑质内注射LPS。免疫组织化学分析显示，LPS引起神经多巴胺能神经元的显著损失，肌苷处理减轻了这种损失。LPS增加了iba1阳性小胶质细胞中NLRP3的表达，肌苷可减弱这种表达。这些发现表明肌苷可以通过改善NLRP3炎性体活性来拯救lps诱导的损伤神经元。因此，肌苷可以作为神经炎性疾病如帕金森病的干预手段。

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引用次数: 0

Moderate prenatal alcohol exposure alters GABAergic transmission and the actions of acute alcohol in the medial central amygdala of adolescent rats 适度的产前酒精暴露改变了青春期大鼠中央杏仁核内侧的gaba能传递和急性酒精的作用。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2024-12-24 DOI: 10.1016/j.neuropharm.2024.110283

Sarah E. Winchester , Marvin R. Diaz

Individuals with prenatal alcohol exposure (PAE) are at a higher risk for developing alcohol use disorder (AUD). Using a rat model of moderate PAE (mPAE) on gestational day 12 (G12; ∼2nd trimesters in humans), a critical period for amygdala development, we have shown disruptions in medial central amygdala (CeM) function, an important brain region associated with the development of AUD. In addition to this, acute ethanol (EtOH) increases GABA transmission in the CeM of rodents in a sex-dependent manner, a mechanism that potentially contributes to alcohol misuse. How mPAE alters acute alcohol's effects within the CeM is unknown. Given these findings, we investigated how mPAE may interact with acute alcohol to alter neuronal and synaptic mechanisms in the CeM of adolescent rats in order to understand PAE-induced alcohol-related behaviors. Under basal conditions, mPAE males showed reduced rheobase, indicative of reduced excitability, and females showed a reduction in GABA transmission, indicated by lower spontaneous inhibitory postsynaptic currents (sIPSCs). We found that acute EtOH increased sIPSCs in control males at the middle concentration (66 mM), while mPAE males showed increased sIPSCs only at the highest tested concentration (88 mM). Adolescent females, regardless of PAE status, were largely insensitive to EtOH's effects at all tested concentrations. However, mPAE females showed a significant increase in sIPSCs at the highest tested concentration (88 mM). Overall, these findings support the hypothesis that mPAE leads to sex-specific changes in synaptic activity and neuronal function. Future research is needed to better understand the specific mechanisms by which acute EtOH affects neurotransmission in the adolescent brain of individuals with a history of PAE.

产前酒精暴露（PAE）的个体患酒精使用障碍（AUD）的风险更高。采用妊娠第12天(G12；在人类中，这是杏仁核发育的关键时期，我们已经发现内侧中央杏仁核（CeM）功能中断，这是一个与AUD发展相关的重要大脑区域。此外，急性乙醇（EtOH）以性别依赖的方式增加GABA在啮齿动物CeM中的传递，这一机制可能导致酒精滥用。mPAE如何改变急性酒精在CeM中的作用尚不清楚。鉴于这些发现，我们研究了mPAE如何与急性酒精相互作用，改变青春期大鼠CeM中的神经元和突触机制，以了解pae诱导的酒精相关行为。在基础条件下，mPAE雄性小鼠表现出流变酶降低，表明兴奋性降低，雌性小鼠表现出GABA传递减少，表明自发抑制性突触后电流（sIPSCs）降低。我们发现，在中等浓度（66 mM）的对照男性中，急性EtOH增加了sIPSCs，而在最高浓度（88 mM）的mPAE男性中，sippsc仅增加。无论PAE状态如何，青春期女性在所有测试浓度下对EtOH的影响都不敏感。然而，在最高测试浓度（88 mM）下，mPAE雌性小鼠的sIPSCs显著增加。总的来说，这些发现支持了mPAE导致突触活动和神经元功能的性别特异性变化的假设。未来的研究需要更好地了解急性EtOH影响有PAE病史的青少年大脑神经传递的具体机制。

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引用次数: 0