Abstract
This study was conducted to determine if an oral squamous cell carcinoma alters mRNA expression of serotonin transporter (5-HTT) in the central nervous system. KB cell line derived from a human oral squamous cell carcinoma was inoculated into nude mice, and mRNA expression level of 5-HTT in the dorsal raphe nucleus (DRN) was examined by in situ hybridization when the tumor mass reached to -10% of total body weight. Plasma leptin levels were determined by radioimmunoassay method using a commercial kit. 5-HTT mRNA level was significantly decreased in the DRN of tumor bearing mice, compared to the age-matching non-tumor control. Plasma leptin level decreased concomitantly in tumor bearing mice. These results suggest that oral carcinoma may suppress 5-HTT gene expression in the central nervous system, perhaps in relation with decreased plasma leptin level.
Highlights
Dysregulation of serotonin (5-hydroxytryptamine, 5-HT) system is known to play a role in the pathophysiology of depressive disorders (Maes and Meltzer, 1995; Mann, 1999)
Depression is one of the major symptoms commonly found in cancer patients, and reported to worsen survival of the patients (Goodwin et al, 2004; Klinkenberg et al, 2004)
Tumor bearing mice were sacrificed for 5-HT reuptake transporter (5-HTT) in situ hybridization when the tumor mass reached to -10% of total body weight (n = 6)
Summary
HT) system is known to play a role in the pathophysiology of depressive disorders (Maes and Meltzer, 1995; Mann, 1999). 5-HTT mRNA level in the DRN has been suggested to correlate with plasma leptin level (Jahng et al, 1998; Collin et al, 2000; Johansen et al, 2000). It has been reported that leptin increases brain 5-HT levels in wild-type and ob/ob mice (Harris et al, 1998; Calapai et al, 1999), and that leptin receptors are localized in 5-HT or 5-HTT containing neurons in the DRN (Collin et al, 2000; Finn et al, 2001; HaySchmidt et al, 2001). The DRN expression of 5-HTT mRNA and the plasma leptin level were examined in the mice bearing an oral squamous cell carcinoma, in order to define the molecular mechanism of the pathogenesis of depression in cancer subjects. Mice received free access to standard laboratory food (Purina Rodent Chow, Purina Co., Seoul, Korea) and water (membrane filtered purified water) ad libitum, and were cared according to The Guide for Animal Experiments, 2000, edited by The Korean Academy of Medical Sciences, which is consistent with NIH Guideline for the Care and Use of Laboratory Animals, 1996 revised
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