Function of cytokine in the brain in manifestation of central fatigue and its involvement to the regulation of metabolism

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1. Activation mechanism of latant-TGF-β in the brainBecause matrix metalloproteinases (MMP) are reported to be involved to activation of inacvtive latent-TGF-β, the activity of MMP in the brain were determined in the exercise which caused fatigue. Increases in the expression of MMP-9 were found after exercise in pons, medulla oblongata, mesencephalon, and diencephalon.2. Expression sites of receptors for TGF-β in the rat brain.Type 1 and type 2 receptor for TGF-β were found to be expressed in paraventricular nucleus of hypothalamus (PVH) in the brain by in situ hybridization and immunohistochemical staining.3. Neurochemical studies of mechanism of TGF-β action in the brainMeasurements of the extracellular concentration of neurotransmitters with intracisternal administration of TGF-β were conducted in some regions of rat brain. Following changes were observed : increases in the extracellular concentrations of serotonin and noradrenaline in the ventromedial nucleus of hypothalamus (VMH), decreases in those of serotonin in lateral hypothalamic area (LHA) and medial prefrontal cortex (mPFC). No changes in the extracellular concentration of dopamine was found.4. Mechanism of action of intracisternally administered TGF-β on peripheral tissuesChanges in concentrations of hormones (adrenalin, noradrenaline, insulin, glucagon, and leptin) in serum were measured. No changes was found in these hormones concentrations by intracisternal administration of TGF-b. However, this treatment caused increase in the activity of lipoprotein lipase (LPL) in skeletal muscles of hind legs. In addition, the concentrations of malonyl-CoA which is a key substance of fat metabolism decreased in the liver and red part of gastrocnemius muscle.