title: Effects of aging on glutamate neurotransmission in the substantia nigra of Gdnf heterozygous mice.
abstract: Glial cell line-derived neurotrophic factor (GDNF) helps protect dopaminergic neurons in the nigrostriatal tract. Although the cause of nigrostriatal degeneration is unknown, one theory is that excess glutamate from the subthalamic nucleus results in excitotoxic events in the substantia nigra (SN). Because dopaminergic degeneration is accompanied by a reduction in GDNF, we examined glutamate neurotransmission in the SN using a Gdnf heterozygous mouse model (Gdnf(+/-)) at 8 and 12 months of age. At 8 months, Gdnf(+/-) mice have greater glutamate release and higher basal glutamate levels, which precede the SN dopaminergic degeneration observed at 12 months of age. However, at 12 months, Gdnf(+/-) mice have lower basal levels of glutamate and less glutamate release than wild-type mice. Also at 8 months, Gdnf(+/-) mice have lower levels of glutamate transporter-1 and greater glial fibrillary acidic protein levels in the SN compared with wild-type mice, differences that increase with age. These data suggest that reduced levels of GDNF induce excess glutamate release and dysregulation of glutamate transporter-1, causing excitotoxicity in the SN that precedes dopaminergic degeneration.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Ariana Q
authors.initials: AQ
authors.lastname: Farrand
authors.affiliation: Department of Comparative Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Gregory
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Scofield
authors.affiliation: Department of Comparative Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Helke
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA. Electronic address: boger@musc.edu.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boger
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology / Q000502:physiology*; D000818:Animals; D059290:Dopaminergic Neurons / Q000473:pathology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000172:deficiency* / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D006579:Heterozygote; D008297:Male; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000209:etiology* / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology* / Q000503:physiopathology*; D020531:Subthalamic Nucleus / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology*
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018698:Glutamic Acid
keywords: Glial cell line-derived neurotrophic factor (GDNF); Glutamate; In vivo electrochemistry; Neurodegeneration; Striatum; Substantia nigra