BDNF is necessary for maintenance of noradrenergic innervations in the aged rat brain

• Published in: Neurobiology of aging 2004-03, Vol.25 (3), p.341-348
• Main Authors: Matsunaga, Wataru, Shirokawa, Tetsuya, Isobe, Kenichi
• Format: Article
• Language: English
• Subjects: Aging; Aging - metabolism; Animals; Antibodies - pharmacology; Axons; BDNF; Biological and medical sciences; Brain-Derived Neurotrophic Factor - antagonists & inhibitors; Brain-Derived Neurotrophic Factor - pharmacology; Cell Survival - drug effects; Cell Survival - physiology; Development. Senescence. Regeneration. Transplantation; Drug Administration Routes; F344 rat; Frontal cortex; Frontal Lobe - drug effects; Frontal Lobe - growth & development; Frontal Lobe - metabolism; Fundamental and applied biological sciences. Psychology; Intracerebral infusion; Locus coeruleus; Locus Coeruleus - drug effects; Locus Coeruleus - growth & development; Locus Coeruleus - metabolism; Male; Neural Pathways - drug effects; Neural Pathways - growth & development; Neural Pathways - metabolism; Noradrenergic innervation; Norepinephrine - metabolism; Rats; Rats, Inbred F344; TrkB; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(03)00093-9

In the axon terminals of the locus coeruleus (LC) neurons, a high level of axonal branching was occurred in the middle-aged brain, and the increased branching was maintained in the aged brain. In the present study, we hypothesized that neurotrophic support is necessary for the morphological age-related changes seen in the noradrenergic innervations from the LC to frontal cortex. Through immunohistochemical and quantitative image analyses, we examined the age-dependent effects of brain-derived neurotrophic factor (BDNF) on the noradrenergic axon terminals in the frontal cortex of F344 rats. We continuously infused BDNF into the frontal cortex of young (6-months-old), middle-aged (13-months-old), or aged (25-months-old) rats. Exogenous BDNF infusion caused a marked increase in the density of noradrenergic axons in the aged brain, but no trophic action of BDNF was observed in the young and middle-aged brain. Neutralization of endogenous BDNF with a specific function-blocking antibody to BDNF led to a reduction in noradrenergic axons in the frontal cortex of 19-month-old rats. The present results suggest that BDNF is not involved in the augmentation of noradrenergic innervations in the aging brain, but it is necessary for the maintenance of noradrenergic innervations in the aged brain.