title: Exacerbated loss of cell survival, neuropeptide Y-immunoreactive (IR) cells, and serotonin-IR fiber lengths in the dorsal hippocampus of the aged flinders sensitive line "depressed" rat: Implications for the pathophysiology of depression?
abstract: Impairment of hippocampal neurogenesis has been proposed to provide a cellular basis for the development of major depression. Studies have shown that serotonin (5-HT) and neuropeptide Y (NPY) may be involved in stimulating cell proliferation in the dentate gyrus. The Flinders-sensitive line (FSL) rat represents a genetic model of depression with characterized 5-HT and NPY abnormalities in the hippocampus. Consequently, it could be hypothesized that hippocampal neurogenesis in the FSL rat would be impaired. The present study examined the relationship among 1) number of BrdU-immunoreactive (IR) cells, 2) NPY-IR cells in the dentate gyrus, and 3) length of 5-HT-IR fibers in the dorsal hippocampus, as well as volume and number of 5-HT-IR cells in the dorsal raphé nucleus, in adult and aged FSL rats and control Flinders-resistant line (FRL) rats. Surprisingly, adult FSL rats had significantly more BrdU-IR and NPY-IR cells compared with adult FRL rats. However, aging caused an exacerbated loss of these cell types in the FSL strain compared with FRL. The aged FSL rats also had shortened 5-HT-IR fibers in the dorsal hippocampus, indicative of an impaired 5-HT innervation of this area, compared with FRL. These results suggest that, for "depressed" FSL rats, compared with FRL rats, aging is associated with an excacerbated loss of newly formed cells in addition to NPY-IR cells and 5-HT-IR dendrites in the hippocampus. These observations may be of relevance to the depression-like behavior of the FSL rat and, by inference, to the pathophysiology of depression.
authors.affiliation: Disease Pharmacology, Department of Psychopharmacology, Lundbeck A/S, Valby, Denmark. hhu@lundbeck.com
authors.forename: H
authors.initials: H
authors.lastname: Husum
authors.forename: S
authors.initials: S
authors.lastname: Aznar
authors.forename: S
authors.initials: S
authors.lastname: Høyer-Hansen
authors.forename: M Hald
authors.initials: MH
authors.lastname: Larsen
authors.forename: J D
authors.initials: JD
authors.lastname: Mikkelsen
authors.forename: A
authors.initials: A
authors.lastname: Møller
authors.forename: A A
authors.initials: AA
authors.lastname: Mathé
authors.forename: G
authors.initials: G
authors.lastname: Wörtwein
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic; D001973:Bromodeoxyuridine; D002470:Cell Survival / Q000502:physiology; D003863:Depression / Q000235:genetics / Q000503:physiopathology*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D009412:Nerve Fibers / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D009478:Neuropeptide Y; D012701:Serotonin; D001973:Bromodeoxyuridine