Balan Irina, Grusca Adelina, Chéry Samantha Lucenell, Materia Baylee R, O'Buckley Todd K, Morrow A Leslie
Bowles Center for Alcohol Studies, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Psychiatry, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Life (Basel). 2024 Jul 9;14(7):860. doi: 10.3390/life14070860.
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.
本研究调查了别孕烯醇酮（[3α,5α]3 - 羟基孕烷 - 20 - 酮或3α,5α - 四氢孕酮（3α,5α - THP）；10毫克/千克，腹腔注射）对雄性和雌性嗜酒（P）大鼠伏隔核（NAc）中趋化因子/CX3 - C基序趋化因子配体1（CX3CL1）水平、相关信号转导成分以及小胶质细胞和星形胶质细胞标志物的影响。先前的研究表明，3α,5α - THP可增强雄性P大鼠大脑中抗炎性白细胞介素 - 10（IL - 10）细胞因子的产生，而在雌性大鼠中未观察到类似效果。本研究表明，3α,5α - THP可使雌性P大鼠NAc中的CX3CL1水平升高16%，而雄性大鼠中未观察到显著变化。在雌性大鼠的多个脑区，包括NAc、杏仁核、下丘脑和中脑，均观察到3α,5α - THP诱导的CX3CL1水平升高，而在雄性大鼠中未观察到显著影响。此外，用3α,5α - THP处理的雌性P大鼠在NAc中CX3CL1受体（CX3CR1；48%）和转化生长因子 - β1（TGF - β1；24%）水平显著升高，同时信号转导和转录激活因子1（STAT1；85%）的激活（磷酸化）增强。相反，在雄性P大鼠中未观察到类似变化。此外，3α,5α - THP使雌性和雄性P大鼠NAc中的胶质纤维酸性蛋白（GFAP）水平降低19%，而不影响小胶质细胞标志物离子钙结合衔接分子1（IBA1）和跨膜蛋白119（TMEM119）。这些发现表明，3α,5α - THP增强了雌性P大鼠大脑中的CX3CL1/CX3CR1通路，但在雄性大鼠中未增强，主要影响星形胶质细胞反应性，而未观察到对小胶质细胞激活的影响。
