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Article

Neurosteroid [3α,5α]-3-Hydroxy-pregnan-20-one Enhances the CX3CL1-CX3CR1 Pathway in the Brain of Alcohol-Preferring Rats with Sex-Specificity

by
Irina Balan
1,2,
Adelina Grusca
1,
Samantha Lucenell Chéry
1,3,
Baylee R. Materia
1,
Todd K. O’Buckley
1 and
A. Leslie Morrow
1,2,4,*
1
Bowles Center for Alcohol Studies, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2
Department of Psychiatry, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3
Neuroscience Curriculum, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4
Department of Pharmacology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
*
Author to whom correspondence should be addressed.
Life 2024, 14(7), 860; https://doi.org/10.3390/life14070860 (registering DOI)
Submission received: 24 April 2024 / Revised: 4 June 2024 / Accepted: 3 July 2024 / Published: 9 July 2024
(This article belongs to the Section Physiology and Pathology)

Abstract

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.
Keywords: fractalkine; inflammation; allopregnanolone; chemokines; cytokines fractalkine; inflammation; allopregnanolone; chemokines; cytokines

Share and Cite

MDPI and ACS Style

Balan, I.; Grusca, A.; Chéry, S.L.; Materia, B.R.; O’Buckley, T.K.; Morrow, A.L. Neurosteroid [3α,5α]-3-Hydroxy-pregnan-20-one Enhances the CX3CL1-CX3CR1 Pathway in the Brain of Alcohol-Preferring Rats with Sex-Specificity. Life 2024, 14, 860. https://doi.org/10.3390/life14070860

AMA Style

Balan I, Grusca A, Chéry SL, Materia BR, O’Buckley TK, Morrow AL. Neurosteroid [3α,5α]-3-Hydroxy-pregnan-20-one Enhances the CX3CL1-CX3CR1 Pathway in the Brain of Alcohol-Preferring Rats with Sex-Specificity. Life. 2024; 14(7):860. https://doi.org/10.3390/life14070860

Chicago/Turabian Style

Balan, Irina, Adelina Grusca, Samantha Lucenell Chéry, Baylee R. Materia, Todd K. O’Buckley, and A. Leslie Morrow. 2024. "Neurosteroid [3α,5α]-3-Hydroxy-pregnan-20-one Enhances the CX3CL1-CX3CR1 Pathway in the Brain of Alcohol-Preferring Rats with Sex-Specificity" Life 14, no. 7: 860. https://doi.org/10.3390/life14070860

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