title: Age-dependent changes in projections from locus coeruleus to hippocampus dentate gyrus and frontal cortex.
abstract: Age-dependent changes in noradrenergic innervations of the hippocampal dentate gyrus (DG) and the frontal cortex (FC) have been studied in male F344 rats. The projections from the nucleus locus coeruleus (LC) to DG or FC with advancing age (from 7 to 27 months) in rats have been quantified by electrophysiological and immunohistochemical methods. In the electrophysiological study, we observed that the percentage of LC neurons activated antidromically by electrical stimulation (P-index) of DG or FC decreased with age. We found that the percentage of LC neurons showing multiple antidromic latencies (M-index), which suggests axonal branching of individual LC neurons, increased markedly between 15 and 17 months in DG or FC. In DG, the M-index increased steadily between 15 and 24 months. In contrast, the increased M-index in FC was maintained until 24 months. The increased M-index in both targets declined at 27 months. These results suggest that LC neurons give rise to axonal branching following the loss of projections to DG or FC with age. In the immunohistochemical study, the density of dopamine-beta-hydroxylase-positive axonal varicosities was measured in molecular, granule cell and polymorphic layers of DG. The density in the polymorphic layer significantly decreased in the earlier stage of ageing (7-19 months), whilst the density in the molecular and granule cell layers decreased in the later stage (27 months). These findings suggested that a layer-specific decline occurred with age in the noradrenergic axon terminals in DG.
authors.affiliation: Department of Basic Gerontology, National Institute for Longevity Sciences, Gengo 36-3, Morioka-cho, Obu 474-0031, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishida
authors.forename: T
authors.initials: T
authors.lastname: Shirokawa
authors.forename: O
authors.initials: O
authors.lastname: Miyaishi
authors.forename: Y
authors.initials: Y
authors.lastname: Komatsu
authors.forename: K
authors.initials: K
authors.lastname: Isobe
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D048429:Cell Size / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology* / Q000254:growth & development; D004299:Dopamine beta-Hydroxylase / Q000032:analysis; D004594:Electrophysiology; D005625:Frontal Lobe / Q000166:cytology* / Q000254:growth & development; D008125:Locus Coeruleus / Q000166:cytology* / Q000254:growth & development; D008297:Male; D009434:Neural Pathways; D009474:Neurons / Q000201:enzymology; D009638:Norepinephrine / Q000502:physiology; D017729:Presynaptic Terminals / Q000737:chemistry / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000502:physiology
chemical_list: D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine