Striatal trophic activity is reduced in the aged rat brain

Our previous studies demonstrated that the survival of a mesencephalic graf t was reduced in aged animals suggesting an age-related decline in target-d erived neurotrophic activity. We tested this hypothesis by examining dopami ne (DA) and trophic activities from the striatum of intact or unilateral 6- hydroxydopamine (6-OHDA) lesioned rats of increasing age. Fisher 344 rats w ere 4, 12, 18, and 23 months old (m.o.) at sacrifice. Half the animals had received unilateral 6-OHDA lesions of the mesostriatal DA pathway 8 weeks e arlier. Striatal tissue punches were analyzed for DA, homovanillic acid (HV A), and DA activity (HVA/DA) using HPLC. The remainder of the striatal tiss ue was homogenized to generate tissue extracts which were added to E14.5 ve ntral mesencephalic cultures to test trophic activity. In the non-lesioned animals, striatal DA was reduced and striatal DA activity was increased in the 18 and 23 m.o. animals relative to the 4 and 12 m.o. animals. Striatal trophic activity was inversely related to age. In the lesioned animals, str iatal DA ipsilateral to 6-OHDA infusion was below detection limits while th e contralateral striatum exhibited age-related changes in DA similar to tho se seen in the non-lesioned animals. In 4 m.o. lesioned rats, striatal trop hic activity ipsilateral to 6-OHDA infusion was elevated by 26% relative to the contralateral side. The ipsi/contra-lateral differences in striatal tr ophic activity were reduced in 12 m.o. animals and absent in the 18 and 23 m.o. groups. These data suggest that advancing age is associated with a red uction in striatal DA as well as trophic activity. Moreover, the aged stria tum loses its ability to biochemically and trophically compensate for DA re duction and therefore may represent a more challenging environment for the survival, growth, and function of a fetal graft. (C) 2000 Published by Else vier Science B.V. All rights reserved.