Effects of intraventricular substantia nigra allografts as a function of donor age

Abstract

Transplantation of fetal substantia nigra into the brain can alleviate some of the manifestations of animal models of Parkinson's disease. The purpose of the present experiment was to determine the optimal embryonic donor age for solid tissue substantia nigra grafts. Rats with unilateral substantia nigra lesions were tested for rotational behavior in response to apomorphine. Animals then received intraventricular grafts of ventral mesencephalon from fetal donors of 11, 13, 15, 17, or 19 days gestational age, and were tested for rotational behavior 6 and 12 weeks after transplantation. After 12 weeks, animals receiving grafts from donors of 11 through 17 days gestation showed similar decreases (means= 42−58%) in rotation. All 4 groups showed greater decreases in rotation than the 19 day group (17%). In both the 11 and 13 day groups, however, there were substantial decreases in rotational behavior from the 6th to the 12th week testing periods. This study confirms that during a critical period of rat fetal development, between 17 and 19 days gestational age, the substantia nigra loses much of its ability to produce functional effects after transplantation. Grafts from very immature donors did not, however, produce markedly greater effects, and the youngest grafts required more time for the development of maximal effects.