| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
"Psychogenic fever" is one of the most common psychosomatic diseases. However, it is still unknown how psychological stress increases core body temperature (Tc) in these patients. Therefore, to elucidate the mechanisms of psychological stress-induced hyperthermia, the following experiments were conducted.
(1) To determine the brain regions crucial for prostaglandin E2 (PGE2)-induced fever, I compared lipopolysaccharide (LPS)-induced Fos-immunoreactivity (Fos-ir) positive cell expression between the EP3 receptor gene knockout (KO) mice and wild type (WT) mice. LPS (10 μg/kg, intraperitoneally) increased Tc (1.0℃) and induced Fos-ir positive cells in the intermediolateral cell column only in the WT mice. Fos-ir positive cells were observed in the ventromedial preoptic area (VMPO) and the raphe pallidus nucleus (RPa) in both mice.
(2) To investigate if psychological stress activates brain nuclei that are activated during LPS-induced fever, I observed Fos-ir expression in the VMPO and the RPa in rats. Cage exchange stress increased Tc (0.9℃) and induced Fos-ir positive cells in the RPa but not in the VMPO.
(3) To assess the involvement of cytokines and PGE2 in the hyperthermia of "psychogenic fever" patients, I investigated the effect of aspirin on Tc and compared blood levels of pyrogenic cytokines such as IL-1, 11-6, and MIP-1α between before and after treatment. Aspirin (660mg, p.o., twice a day) failed to attenuate the hyperthermia. Blood cytokine levels were not different between the pre (37.6℃) and post-treatment (36.8℃). To note, four weeks administration of paroxetine, a selective serotonin (5-HT) reuptake inhibitor, significantly improved persistent hyperthermia.
These findings suggest that (1) the VMPO may not be involved in PSH, (2) psychological stress increases Tc via cytokines- or PGE2-independent mechanisms, and (3) central 5-HTergic hypofunction may account for stress-induced, persistent hyperthermia.
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