The Noradrenergic System of Aged GDNF Heterozygous Mice
Abstract:Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for noradrenergic (NE) neurons of the pontine nucleus locus coeruleus (LC). Decreased function of the LC-NE neurons has been found during normal aging and in neurodegenerative disorders. We have previously shown that GDNF participates in the differentiation of LC-NE neurons during development. However, the continued role of GDNF for LC-NE neurons during maturation and aging has not been addressed. We examined alterations in aged mice that were heterozygous for the GDNF gene (Gdnf+/−). Wild-type (Gdnf+/+) and Gdnf+/− mice (18 months old) were tested for locomotor activity and brain tissues were collected for measuring norepinephrine levels and uptake, as well as for morphological analysis. Spontaneous locomotion was reduced in Gdnf+/− mice in comparison with Gdnf+/+ mice. The reduced locomotor activity of Gdnf+/− mice was accompanied by reductions in NE transporter activity in the cerebellum and brain stem as well as decreased norepinephrine tissue levels in the LC. Tyrosine hydroxylase (TH) immunostaining demonstrated morphological alterations of LC-NE cell bodies and abnormal TH-positive fibers in the hippocampus, cerebellum, and frontal cortex of Gdnf+/− mice. These findings suggest that the LC-NE system of Gdnf+/− mice is impaired and suggest that GDNF plays an important role in continued maintenance of this neuronal system throughout life.
Document Type: Research Article
Affiliations: 1: *Department of Physiology and Neuroscience and the Center on Aging, Medical University of South Carolina, Charleston, SC 29425 2: §Department of Neurology, Medical University of South Carolina, Charleston, SC 29425 3: ‡Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425 4: ¶National Institute on Drug Abuse, IRP, Baltimore, MD 21224 5: #Chandler Medical Center, Department of Anatomy & Neurobiology, University of Kentucky, Lexington, KY 40536-0098
Publication date: 2003-01-01
- Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.