L-dopa-responsive movement disorder caused by Nocardia asteroides localized in the brains of mice

Abstract

Nocardia asteroides can cause infections in the brain of humans and a variety of animals. In mice, invasion of the central nervous system results in specific neurologic signs. Following intravenous injection of various doses of log-phase N. asteroides GUH-2 into female BALB/c mice, localization and growth of nocardial cells within the brains were determined, histopathological sections were prepared, and Nissl substance and tyrosine hydroxylase immunoreactivity were observed. Mice were monitored for the development of neurologic signs, and their responsiveness to L-dopa was determined. It was shown that nocardial cells became localized within specific regions of the brain and then underwent rapid growth followed by a delayed clearance, and there was no inflammatory response at the site of invasion for 24 h. Mice that received a subclinical dose of nocardiae developed specific neurologic signs that emerged following the elimination of nocardial cells from the brain. On the basis of the specific signs, mice could be divided into distinct groups. One group consisted of animals that had a form of hemiparesis that did not respond to L-dopa. They expressed a deviation of the head and a tendency to roll, and when suspended by the tail they would spin rapidly. The second group of mice developed a rhythmic, uncontrolled vertical shake of the head (four to five times per s) tremulous movement, stooped posture, restlessness, and no signs of hemiparesis. The head shakes were temporarily stopped by treatment with L-dopa. Mice that expressed head shakes had a loss of Nissl substance and tyrosine hydroxylase immunoreactivity in the neurons of the substantia nigra and ventral tegmental areas of the brain. Hyaline inclusion bodies that resembled Lewy bodies were found in the neurons of mice with head shake 1 month after infection. Therefore, mice infected with N. asteroides may serve as a model for studying parkinsonian signs and other degenerative diseases involving extrapyramidal and pyramidal systems.