Biomaterial Database

Glial cell line-derived neurotrophic factor induces the dopaminergic and cholinergic phenotype and increases locomotor activity in aged Fischer 344 rats. 1997

P A Lapchak, and P J Miller, and S Jiao

AMGEN Inc., Department of Neuroscience, Thousand Oaks, CA 91320-1789, U.S.A.

Glial cell line-derived neurotrophic factor has been shown to affect dopaminergic and cholinergic neuron markers and functions in young rats. However, it is not known if the response to exogenous glial cell line-derived neurotrophic factor is augmented during normal aging. Thus, the effects of chronic intraventricular infusions of glial cell line-derived neurotrophic factor were determined in young adult (three-months-old) and aged (24-months-old) Fischer 344 (F344) male rats. The effects of glial cell line-derived neurotrophic factor were compared to the effects of the neurotrophin nerve growth factor. Growth factors were administered at a dose of 10 mg/day for 14 days. Locomotor activity and weight changes were also examined in all rats. Aged F344 rats showed significantly reduced (by 75-80%) locomotor activity compared to young rats. In glial cell line-derived neurotrophic factor-treated aged and young rats there was significantly increased (242% and 149%, respectively) locomotor activity measured at seven days. There was also a significant increase in locomotor activity measured 14 days after the start of infusion. Both glial cell line-derived neurotrophic factor and nerve growth factor reduced weight gain by 10% in young and old F344 rats. Two weeks following the start of nerve growth factor or glial cell line-derived neurotrophic factor administration the brains were used for neurochemical analyses. Glial cell line-derived neurotrophic factor significantly increased tyrosine hydroxylase activity in the substantia nigra and striatum of aged rats and in the substantia nigra of young rats. Nerve growth factor treatment did not significantly affect tyrosine hydroxylase activity. However, glial cell line-derived neurotrophic factor and nerve growth factor increased choline acetyltransferase activity in the septum, hippocampus, striatum and cortex of aged rats and in the hippocampus and striatum of young rats to a comparable degree. These findings indicate that specific dopaminergic and cholinergic neuron populations remain responsive to glial cell line-derived neurotrophic factor during the life span of the rat and may be involved in maintaining phenotypic expression within multiple neuronal populations. Additionally, the glial cell line-derived neurotrophic factor-induced up-regulation of brain neurotransmitter systems may be responsible for increased locomotor activity in F344 rats.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009043	Motor Activity	Body movements of a human or an animal as a behavioral phenomenon.	Activities, Motor,Activity, Motor,Motor Activities
D009414	Nerve Growth Factors	Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.	Neurite Outgrowth Factor,Neurite Outgrowth Factors,Neuronal Growth-Associated Protein,Neuronotrophic Factor,Neurotrophic Factor,Neurotrophic Factors,Neurotrophin,Neurotrophins,Growth-Associated Proteins, Neuronal,Neuronal Growth-Associated Proteins,Neuronotrophic Factors,Neurotrophic Protein,Neurotrophic Proteins,Proteins, Neuronal Growth-Associated,Factor, Neurite Outgrowth,Factor, Neuronotrophic,Factor, Neurotrophic,Factors, Nerve Growth,Factors, Neurite Outgrowth,Factors, Neuronotrophic,Factors, Neurotrophic,Growth Associated Proteins, Neuronal,Growth-Associated Protein, Neuronal,Neuronal Growth Associated Protein,Neuronal Growth Associated Proteins,Outgrowth Factor, Neurite,Outgrowth Factors, Neurite,Protein, Neuronal Growth-Associated
D009419	Nerve Tissue Proteins		Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009457	Neuroglia	The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.	Bergmann Glia,Bergmann Glia Cells,Bergmann Glial Cells,Glia,Glia Cells,Satellite Glia,Satellite Glia Cells,Satellite Glial Cells,Glial Cells,Neuroglial Cells,Bergmann Glia Cell,Bergmann Glial Cell,Cell, Bergmann Glia,Cell, Bergmann Glial,Cell, Glia,Cell, Glial,Cell, Neuroglial,Cell, Satellite Glia,Cell, Satellite Glial,Glia Cell,Glia Cell, Bergmann,Glia Cell, Satellite,Glia, Bergmann,Glia, Satellite,Glial Cell,Glial Cell, Bergmann,Glial Cell, Satellite,Glias,Neuroglial Cell,Neuroglias,Satellite Glia Cell,Satellite Glial Cell,Satellite Glias
D009928	Organ Specificity	Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.	Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D011916	Rats, Inbred F344	An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes.	Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D001835	Body Weight	The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	Body Weights,Weight, Body,Weights, Body
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell