Abstract
It is uncertain how lack of dystrophin results in muscle necrosis and mental retardation in Duchenne muscular dystrophy (DMD). To find a cellular event subsequent to the lack of dystrophin, fatigability of neuromuscular junction in diaphragm and spatial learning were studied with weaning (3-4 wks-old) muscular dystrophy (mdx) mice with little muscle degeneration and the control mice. A half decay time of contraction of isolated diaphragm produced by the phrenic nerve stimulation at 100 Hz was greater significantly in the weaning mdx mice than the control mice, while it was the same between them when the diaphragm was stimulated directly. This finding may be accounted for by assuming a greater number of acetylcholine receptors in the diaphragm of the weaning mdx mice than the control mice, since a partial blockade of acetylcholine receptors by D-tubocrarine and 1,3-PBIT dihydrobromide shortened the half decay time. In the Morris water maze, mice were given a total of three trials a day on 4 consecutive days. Escape latency, the time taken for the animal to climb onto a hidden platform (7 cm diameter) after being placed in the water in a pool, shortened during the training days. The escape latency on the 4th day was greater in order of weaning mdx mice > adult (10-14 wks-old) mdx mice > weaning control mice = adult control mice, suggesting that spatial learning is severely impaired in the weaning mdx mice. It is quite important to determine if abnormal distribution of nicotinic-acetylcholine receptor is a link between the lack of dystrophin and various symptoms in DMD. [Jpn J Physiol 55 Suppl:S230 (2005)]
