Psychopharmacology · 2025
Neurosteroid (3α,5α)3-hydroxypregnan-20-one enhancement of anti-inflammatory chemokine CX3CL1 exhibits sex, brain region, and cellular specificity in alcohol-preferring rats.
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Chéry Samantha Lucenell, Materia Baylee R, O'Buckley Todd K, Balan Irina, Morrow A Leslie
Аннотация
RATIONALE: The neurosteroid [3α,5α]3-hydroxypregnan-20-one (3α,5α-THP) possesses anti-inflammatory properties that modulate chemokine and cytokine expression following the activation of toll-like receptors. The expression of fractalkine (CX3CL1), a chemokine involved in cross-communication in neurons, microglia, and astroglia, varies with 3α,5α-THP treatments, prompting further investigation.
OBJECTIVES: This study investigates the influence of 3α,5α-THP on fractalkine expression in neurons, microglia, and astroglia in male and female alcohol-preferring P rats.
METHODS: Double-immunofluorescence confocal microscopy against CX3CL1 and markers for neuronal (neuronal nuclear antigen, NeuN), microglial (transmembrane protein 119, TMEM119), and astrocytes (glial fibrillary acidic protein, GFAP) were assessed in the nucleus accumbens (NAc) and central amygdala (CeA) an hour after an intraperitoneal injection of 15 mg/kg 3α,5α-THP.
RESULTS: 3α,5α-THP increases the expression of CX3CL1 in female (41%) and male (52%) CeA, decreases it in female NAc (-37%), and does not alter it in the male NAc. Measuring the shared voxel (intersection) between CX3CL1 and cellular markers revealed that 3α,5α-THP significantly decreases only the intersection of CX3CL1 and NeuN in both female (-32%) and male (-30%) NAc, without affecting the intersection with cellular markers in the CeA. 3α,5α-THP did not alter NeuN, TMEM119, or GFAP expression.
CONCLUSIONS: 3α,5α-THP alters the expression of neuronal CX3CL1 in a sex- and brain region-dependent manner. The results clarify the specificity of the effect of 3α,5α-THP on neuroimmune protection in the brain.
OBJECTIVES: This study investigates the influence of 3α,5α-THP on fractalkine expression in neurons, microglia, and astroglia in male and female alcohol-preferring P rats.
METHODS: Double-immunofluorescence confocal microscopy against CX3CL1 and markers for neuronal (neuronal nuclear antigen, NeuN), microglial (transmembrane protein 119, TMEM119), and astrocytes (glial fibrillary acidic protein, GFAP) were assessed in the nucleus accumbens (NAc) and central amygdala (CeA) an hour after an intraperitoneal injection of 15 mg/kg 3α,5α-THP.
RESULTS: 3α,5α-THP increases the expression of CX3CL1 in female (41%) and male (52%) CeA, decreases it in female NAc (-37%), and does not alter it in the male NAc. Measuring the shared voxel (intersection) between CX3CL1 and cellular markers revealed that 3α,5α-THP significantly decreases only the intersection of CX3CL1 and NeuN in both female (-32%) and male (-30%) NAc, without affecting the intersection with cellular markers in the CeA. 3α,5α-THP did not alter NeuN, TMEM119, or GFAP expression.
CONCLUSIONS: 3α,5α-THP alters the expression of neuronal CX3CL1 in a sex- and brain region-dependent manner. The results clarify the specificity of the effect of 3α,5α-THP on neuroimmune protection in the brain.