Evaluation of 5-hydroxytryptamine (5-HT) on Cognitive Function in Rats with Gut-Brain Axis Dysfunction Following...

To investigate how 5-hydroxytryptamine (5-HT) modulates acceleration-induced gut-brain axis dysfunction (10 gravitational acceleration [Gz]) and its cognitive impacts in rats, focusing on microbiota-immune interactions and hippocampal neuroinflammation. Sixty male Sprague-Dawley rats were divided into four groups (n = 15/group): Control (0 Gz); + 10 Gz (acceleration exposure via animal centrifuge at 10 Gz for 5 min); 5-HT-Enriched + 10Gz (tryptophan 2.4%) and5-HT-Depleted + 10Gz (tryptophan 0%). Cognitive assessments (Morris water maze, open-field test) and sample collection were performed at 6, 24, and 72 h post-exposure. Serum 5-HT, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) levels were quantified by enzyme-linked immunosorbent assay (ELISA). Hippocampal CA1 microglial activation was assessed by CD11b/Iba-1 immunofluorescence. Fecal microbiota composition was analyzed via 16S ribosomal RNA sequencing (V3-V4 region, QIIME2 pipeline).  + 10 Gz group showed prolonged escape latency (72 h: 111.88 ± 7.96 s vs. control 32.15 ± 5.43 s, P < 0.001) and reduced open-field exploration (central crossingsat 6 h: 9.60 ± 2.88 vs. control 21.4 ± 8.26, P < 0.05), which was reversed by 5-HT supplementation (escape latency at 72 h: 34.12 ± 4.21 s, P < 0.001). + 10 Gz increased Firmicutes/Bacteroidetes ratio (62.1%:18.7% vs. control 48.3%:32.5%), while 5-HT-Enriched + 10Gz enhanced Lactobacillus abundance (21.3% vs. + 10Gz 8.7%, P < 0.05). Serum TNF-α (72 h: 5.56 ± 0.40 pg/mg vs. control 0.12 ± 0.03 pg/mg) and IL-1β (4.21 ± 0.32 pg/mg vs. 0.08 ± 0.01 pg/mg) surged following acceleration exposure (P < 0.001). 5-HT supplementation significantly attenuated these cytokine elevations, with TNF-α reduced to 8.34 ± 0.19 pg/mg (P = 0.003) and IL-1β to 4.41 ± 0.47 pg/mg (P = 0.02) compared to the + 10Gz group. Meanwhile, hippocampal CA1 microglial activation progressively increased (CD11b + area: 6 h 28.3 ± 3.1% → 72 h 45.6 ± 4.8%, P < 0.001), which was attenuated by 5-HT (19.7 ± 2.3%, P < 0.01). 5-HT ameliorates acceleration-induced cognitive deficits by rebalancing gut microbiota and suppressing CA1-specific neuroinflammation, suggesting therapeutic potential for gut-brain axis disorders.