Senescence accelerated mice (SAM), a murine model of age-related deterioration in learning ability, were studied neurochemically in terms of the central histaminergic neuron system. Histamine levels in the forebrain and midbrain of SAM mice increased with aging. The forebrain histamine levels in old SAM-P/8 (accelerated senescence prone) mice were significantly higher than those in old SAM-R/1 (accelerated senescence resistant) mice. Experiments with α-fluoromethylhistidine, a specific inhibitor of histamine synthesis, suggested that the increase in histamine levels in the forebrain of P/8 mice was associated with histamine derived from mast cells. The binding of [3H]-pyrilamine to membrane fractions of various regions of brain were almost the same between SAM and ddY mice. The histidine decarboxylase activity in the brain of old P/8 mice was significantly lower than that of old R/1 and young P/8, R/1 and ddY mice. These results indicate the possibility of damage to the central histaminergic neuron system in SAM mice, whereas the mast cell-derived histamine content of the brain was increased in SAM mice.
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|Published - 1992