Striatal trophic activity is reduced in the aged rat brain.
Our previous studies demonstrated that the survival of a mesencephalic graft was reduced in aged animals suggesting an age-related decline in target-derived neurotrophic activity. We tested this hypothesis by examining dopamine (DA) and trophic activities from the striatum of intact or unilateral 6-hydroxydopamine (6-OHDA) lesioned rats of increasing age. Fisher 344 rats were 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 earlier. Striatal tissue punches were analyzed for DA, homovanillic acid (HVA), and DA activity (HVA/DA) using HPLC. The remainder of the striatal tissue was homogenized to generate tissue extracts which were added to E14.5 ventral 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, striatal DA ipsilateral to 6-OHDA infusion was below detection limits while the contralateral striatum exhibited age-related changes in DA similar to those seen in the non-lesioned animals. In 4 m.o. lesioned rats, striatal trophic activity ipsilateral to 6-OHDA infusion was elevated by 26% relative to the contralateral side. The ipsi/contra-lateral differences in striatal trophic 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 reduction in striatal DA as well as trophic activity. Moreover, the aged striatum loses its ability to biochemically and trophically compensate for DA reduction and therefore may represent a more challenging environment for the survival, growth, and function of a fetal graft.
Ling
Z D
ZD
Department of Pharmacology, Rush-Presbyterian-St. Luke's Medical Center, Tech 2000, Suite 260, 2242 West Harrison Street, Chicago IL, USA.
Collier
T J
TJ
Sortwell
C E
CE
Lipton
J W
JW
Vu
T Q
TQ
Robie
H C
HC
Carvey
P M
PM
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D007839:Functional Laterality; D006719:Homovanillic Acid / Q000378:metabolism; D008636:Mesencephalon / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D014020:Tissue Extracts / Q000494:pharmacology
D014020:Tissue Extracts; D016627:Oxidopamine; D004298:Dopamine; D006719:Homovanillic Acid