Effects of age and GDNF on noradrenergic innervation of the hippocampal formation: studies from intraocular grafts.
Recent studies have suggested that factors in the target tissue influence the degree of plasticity and regeneration following aging and/or specific insults. We have investigated whether young or aged targets differ in their noradrenergic innervation from fetal locus coeruleus (LC) neurons, and also if a specific growth factor, glial cell line-derived neurotrophic factor (GDNF) can affect this innervation pattern. Tissue pieces of fetal brainstem and young (3 months) or old (18 months) iris tissue were transplanted simultaneously into the anterior chamber of the eye of adult hosts. We found that aged iris transplants became innervated to a significantly lesser degree by the cografted LC neurons than young iris transplants. Fetal hippocampal tissue was then grafted to adult hosts, and a fetal brainstem graft containing LC neurons was placed adjacent to the first graft, either at 3 or 21 months post-grafting. Thus, old/young chimeras of the noradrenergic coeruleo-hippocampal pathway were created. Aged hippocampal grafts received a much less dense innervation from co-grafted LC neurons than young hippocampal grafts. Tyrosine hydroxylase-positive-immunoreactive innervation was only found in the outskirts of aged grafts, while the young hippocampal grafts contained an even innervation pattern. The innervation density of hippocampal grafts was significantly enhanced by GDNF treatment. These findings demonstrate that target-derived factors may regulate neuronal plasticity, and that the age of the target is more important for innervation properties than the age of the neuron innervating a particular target.
Granholm
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AC
Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA. granholm@musc.edu
Helt
C
C
Srivastava
N
N
Backman
C
C
Gerhardt
G A
GA
D000375:Aging / Q000502:physiology*; D000818:Animals; D016380:Brain Tissue Transplantation / Q000502:physiology; D005123:Eye; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006085:Graft Survival / Q000502:physiology; D006624:Hippocampus / Q000196:embryology / Q000502:physiology* / Q000637:transplantation; D007498:Iris / Q000637:transplantation; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D033581:Stem Cell Transplantation; D014446:Tyrosine 3-Monooxygenase
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase