Integrating neurotrophic and anti-inflammatory pathways: press-needle acupuncture as a multi-target therapy for adolescent depression

BACKGROUND: Press needle therapy, may alleviate depressive-like behaviors. METHODS: = 8): Normal control group (CON), Chronic Unpredictable Mild Stress(CUMS) group (CUMS), Press-needle group (PN), and Fluoxetine group (FLX). A depressive-like model was established by the CUMS paradigm for 28 consecutive days. Body weights were recorded at baseline and on Days 7, 14, and 28. Behavioral assessments were conducted, including: open field test (OFT), elevated plus maze (EPM), forced swim test (FST), and sucrose preference test (SPT). Protein expression levels of BDNF, CREB, TrkB, AKT, PKA, 5-HT1A receptor, and 5-HT2C receptor in hippocampal tissues were quantified by Western blot analysis. Concurrently, enzyme-linked immunosorbent assay (ELISA) measured the concentrations of PI3K and AKT in hippocampal homogenates, and IL-6 and TNF-α in both hippocampal homogenates and serum samples. Hippocampal mRNA expression levels of 5-HTT, 5-HT1A receptor, TrkB, MAPK, and BDNF were determined using quantitative real-time polymerase chain reaction (RT-qPCR). For morphological assessment, hematoxylin and eosin (H&E) staining was performed on paraffin-embedded hippocampal sections. RESULTS: Press-needle ameliorated depressive-like behaviors in CUMS-exposed rats, restored body weight gain and improved behavioral performance. The treatment upregulated the hippocampal BDNF/TrkB/CREB signaling pathway, increasing BDNF, TrkB, CREB, AKT, and PI3K in the hippocampus. The therapy modulated serotonergic neurotransmission by increasing hippocampal 5-HTT expression, while downregulating 5-HT1A and 5-HT2C receptors and PKA. Notably, press-needle exerted anti-neuroinflammatory effects, reducing hippocampal and serum levels of TNF-α and IL-6. Histopathological analysis confirmed its neuroprotective efficacy, demonstrating attenuated neuronal damage in hippocampal tissues.