ArticleFrontiers in physiology2026
TPM-like manipulations exerted an antidepressant effect and regulated amino acid metabolism and GHR/IGF-1 pathway in the liver in adolescent female CUMS rats.
Article in Frontiers in physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: To explore whether traditional-pediatric-massage-like (TPM-like) manipulations exert antidepressant effects and regulate amino acid metabolism and GHR/IGF-1 pathway in the liver from the liver-brain axis perspective in adolescent female CUMS rats. Methods: Female Sprague-Dawley rats (3-4 weeks) were randomly divided into four groups (n=7-8): control (CON), chronic unpredictable mild stress (CUMS), CUMS + TPM-like manipulations (TPM), and CUMS + fluoxetine (FLX). Depressive-like behaviors were assessed using the sucrose preference test, open field test, and Morris water maze test. Hippocampal insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) expressions were detected by qRT-PCR and WB. Hippocampal and hepatic tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) were assessed by qRT-PCR, and hepatic histopathology was evaluated by HE staining. Hepatic growth hormone receptor (GHR) and IGF-1 expressions were detected by qRT-PCR and WB. Liver metabolism was assessed by UPLC-MS/MS. Hepatic L-Aspartic Acid and plasma IGF-1, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured by ELISA. Associations among liver metabolites, L-Aspartic Acid, depressive-like behaviors, and GHR/IGF-1 expression were analyzed. Results: CUMS induced depressive-like behaviors, inflammation and reduced expressions of IGF-1 and IGF-1R in the hippocampus in adolescent female rats. Moreover, CUMS significantly disturbed amino acid metabolism, particularly lowered the concentration of L-Aspartic Acid, reduced the expressions of GHR/IGF-1 pathway in the liver, induced liver inflammation. TPM-like manipulations exerted antidepressant effects, maintained amino acid metabolic homeostasis in the liver and mitigated inflammation in both the hippocampus and the liver. Importantly, the concentration level of L-Aspartic Acid was negatively related to the severity of depressive-like behaviors, positively related to the expression levels of IGF-1 and IGF-1R in the hippocampus as well as GHR and IGF-1 in the liver. Conclusion: TPM-like manipulations prevented CUMS-induced depressive-like behaviors, increased concentration of L-Aspartic Acid, increased the expressions of GHR and IGF-1 in the liver, increased the expressions of IGF-1 and IGF-1R, and inhibited inflammation in the hippocampus in adolescent female rats. However, further study is warranted to draw confirmative results related to liver-brain axis.
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