Hippocampal neurotrophin levels after injury: Relationship to the age of the hippocampus at the time of injury.
Aging impairs the competence of the hippocampus for synaptic reorganization after injury. This potentially is due to the inability of the aging hippocampus to up-regulate the critical neurotrophic factors for prolonged periods after injury to levels at which they can stimulate neurite outgrowth and facilitate synaptic reorganization. We hypothesize that the concentrations of neurotrophins in the hippocampus after injury depend on the age at the time of injury. We quantified the concentrations of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) in the hippocampus of young, middle-aged, and aged Fischer 344 rats at 4 days after kainic acid (KA)-induced injury. In comparison with the age-matched intact hippocampus, the KA-lesioned hippocampus exhibited increased levels of BDNF and NGF in all three age groups. In contrast, the NT-3 concentration was unaltered after KA lesion. Notwithstanding similar percentage increases in BDNF after injury, the lesioned middle-aged and aged hippocampus contained 45-52% less BDNF than the lesioned young hippocampus. NGF and NT-3 levels after injury were comparable across the three age groups, however. Furthermore, lower BDNF concentration in the injured aging hippocampus was associated with normal astrocytic response but significantly diminished microglial reaction. Thus, in comparison with the injured young hippocampus, the injured aging hippocampus contains considerably less BDNF but similar levels of NGF and NT-3. Lower BDNF levels in the injured aging hippocampus might underlie the diminished spontaneous healing response observed in the aging hippocampus after injury, particularly in terms of synaptic reorganization and dentate neurogenesis.
Medical Research Service, Veterans Affairs Medical Center, Durham, North Carolina 27710, USA. ashok.shetty@duke.edu
Ashok K
AK
Shetty
Muddanna S
MS
Rao
Bharathi
B
Hattiangady
Vandana
V
Zaman
Geetha A
GA
Shetty
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001923:Brain Chemistry / Q000187:drug effects; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D007276:Injections, Intraventricular / Q000379:methods; D007608:Kainic Acid; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D007608:Kainic Acid