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.
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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.