Morphologic alterations of choline acetyltransferase-positive neurons in the basal forebrain of aged behaviorally characterized fisher 344 rats

David M. Armstrong, Roxanne Sheffield, Gyorgy Buzsaki, Karen S. Chen, Louis B. Hersh, Bruce Nearing, Fred H. Gage

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

We examined Fisher 344 female rats aged 6, 27, and 33 months old. Prior to sacrifice and morphometric analyses of forebrain cholinergic neurons all rats underwent behavioral characterization in a spatial learning task using the Morris water maze. Performance on the spatial task permitted subsequent grouping of the 27- and 33-month-old animals into impaired groups. Importantly, the percentage of animals that displayed spatial impairments increased sharply with advancing age. Quantitative assessment of the size and density of choline acetyltransferase (ChAT) - positive neurons throughout the basal forebrain revealed a significant enlargement of forebrain cholinergic neurons within 27-month-old nonimpaired rats compared to 6-month-old rats and 27- and 33-month-old impaired animals. This increase in size was most noted in the medial septum and nucleus of the diagonal band. Significant decreases in the density of ChAT-positive neurons was observed only in the nucleus of the diagonal band of 27-month-old impaired rats compared to 6-month-old controls. Although the significance of enlarged forebrain cholinergic neurons is unclear, we discuss the possibility that within aged rodents neuronal swelling is an active event and represents an early manifestation of the aging process and may constitute a restorative and/or compensatory event in that these rats are relatively asymptomatic with respect to their behavioral deficits. In addition, we discuss in some detail various technical and life effect issues which may vary the outcome of investigations of aged rodents.

Original languageEnglish
Pages (from-to)457-470
Number of pages14
JournalNeurobiology of Aging
Volume14
Issue number5
DOIs
StatePublished - 1993

Bibliographical note

Funding Information:
This work supportbeyd N IH Grants AG05344, AG08206, AG06088, theP EW Foundation, and Athlzeh eimer'Dsi sease and Related Disorders Association.

Funding

This work supportbeyd N IH Grants AG05344, AG08206, AG06088, theP EW Foundation, and Athlzeh eimer'Dsi sease and Related Disorders Association.

FundersFunder number
Greek Association of Alzheimer's Disease and Related Disorders
National Institute on AgingR01AG006088
theP EW Foundation

    Keywords

    • Aged rats
    • Basal forebrain
    • Choline acetyltransferase
    • Morphology
    • Nerve growth factor receptor

    ASJC Scopus subject areas

    • Clinical Neurology
    • Geriatrics and Gerontology
    • Aging
    • General Neuroscience
    • Developmental Biology

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