神经类固醇[3α,5α]-3-羟基孕甾-20-酮能增强嗜酒大鼠脑中的 CX3CL1-CX3CR1 通路,且具有性别特异性

Life Pub Date : 2024-07-09 DOI:10.3390/life14070860
Irina Balan, Adelina Grusca, S. L. Chéry, Baylee R. Materia, T. O’Buckley, A. L. Morrow
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引用次数: 0

摘要

本研究探讨了异孕烯醇酮([3α,5α]3-羟基孕甾-20-酮或 3α,5α-四氢孕甾酮(3α,5α-THP);10毫克/千克,IP)对雄性和雌性酒精偏好大鼠(P)的脑核(NAc)中分叉碱/CX3-C motif趋化因子配体1(CX3CL1)水平、相关信号成分以及小胶质细胞和星形胶质细胞标记物的影响。以前的研究表明,3α,5α-THP 能增强雄性酒精偏好大鼠大脑中抗炎性白细胞介素-10(IL-10)细胞因子的产生,但在雌性大鼠中没有观察到类似的效果。本研究发现,3α,5α-THP 可使雌性 P 型大鼠 NAc 中的 CX3CL1 水平升高 16%,而在雄性大鼠中未观察到明显变化。3α,5α-THP诱导的CX3CL1水平升高在雌性大鼠的多个脑区均可观察到,包括NAc、杏仁核、下丘脑和中脑,而在雄性大鼠中则未发现明显影响。此外,用 3α,5α-THP治疗的雌性P大鼠的CX3CL1受体(CX3CR1;48%)和转化生长因子-β1(TGF-β1;24%)水平明显升高,NAc中信号转导和转录激活因子1(STAT1;85%)的激活(磷酸化)也有所增强。相反,在雄性 P 型大鼠身上没有观察到类似的变化。此外,3α,5α-THP 还能使雌性和雄性 P 型大鼠 NAc 中神经胶质纤维酸性蛋白(GFAP)水平降低 19%,但不会影响小神经胶质标记物电离钙结合适配分子 1(IBA1)和跨膜蛋白 119(TMEM119)。这些研究结果表明,3α,5α-THP 可增强雌性 P 大鼠大脑中的 CX3CL1/CX3CR1 通路,但对雄性 P 大鼠没有影响,主要影响星形胶质细胞的反应性,对小胶质细胞的活化没有观察到影响。
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Neurosteroid [3α,5α]-3-Hydroxy-pregnan-20-one Enhances the CX3CL1-CX3CR1 Pathway in the Brain of Alcohol-Preferring Rats with Sex-Specificity
This study investigates the impact of allopregnanolone ([3α,5α]3-hydroxypregnan-20-one or 3α,5α-tetrahydroprogesterone (3α,5α-THP); 10 mg/kg, IP) on fractalkine/CX3-C motif chemokine ligand 1 (CX3CL1) levels, associated signaling components, and markers for microglial and astrocytic cells in the nucleus accumbens (NAc) of male and female alcohol-preferring (P) rats. Previous research suggested that 3α,5α-THP enhances anti-inflammatory interleukin-10 (IL-10) cytokine production in the brains of male P rats, with no similar effect observed in females. This study reveals that 3α,5α-THP elevates CX3CL1 levels by 16% in the NAc of female P rats, with no significant changes observed in males. The increase in CX3CL1 levels induced by 3α,5α-THP was observed in females across multiple brain regions, including the NAc, amygdala, hypothalamus, and midbrain, while no significant effect was noted in males. Additionally, female P rats treated with 3α,5α-THP exhibited notable increases in CX3CL1 receptor (CX3CR1; 48%) and transforming growth factor-beta 1 (TGF-β1; 24%) levels, along with heightened activation (phosphorylation) of signal transducer and activator of transcription 1 (STAT1; 85%) in the NAc. Conversely, no similar alterations were observed in male P rats. Furthermore, 3α,5α-THP decreased glial fibrillary acidic protein (GFAP) levels by 19% in both female and male P rat NAc, without affecting microglial markers ionized calcium-binding adaptor molecule 1 (IBA1) and transmembrane protein 119 (TMEM119). These findings indicate that 3α,5α-THP enhances the CX3CL1/CX3CR1 pathway in the female P rat brain but not in males, primarily influencing astrocyte reactivity, with no observed effect on microglial activation.
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