title: Exercise-Mediated Increase in Nigral Tyrosine Hydroxylase Is Accompanied by Increased Nigral GFR-α1 and EAAC1 Expression in Aging Rats.
abstract: Exercise may alleviate locomotor impairment in Parkinson's disease (PD) or aging. Identifying molecular responses immediately engaged by exercise in the nigrostriatal pathway and allied tissue may reveal critical targets associated with its long-term benefits. In aging, there is loss of tyrosine hydroxylase (TH) and the glial cell line-derived neurotrophic factor (GDNF) receptor, GFR-α1, in the substantia nigra (SN). Exercise can increase GDNF expression, but its effect on GFR-α1 expression is unknown. Infusion of GDNF into striatum or GFR-α1 in SN, respectively, can increase locomotor activity and TH function in SN but not striatum in aged rats. GDNF may also increase glutamate transporter expression, which attenuates TH loss in PD models. We utilized a footshock-free treadmill exercise regimen to determine the immediate impact of short-term exercise on GFR-α1 expression, dopamine regulation, glutamate transporter expression, and glutamate uptake in 18 month old male Brown-Norway/Fischer 344 F1 hybrid rats. GFR-α1 and TH expression significantly increased in SN but not striatum. This exercise regimen did not affect glutamate uptake or glutamate transporter expression in striatum. However, EAAC1 expression increased in SN. These results indicate that nigral GFR-α1 and EAAC1 expression increased in conjunction with increased nigral TH expression following short-term exercise.
authors.affiliation: Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center , Shreveport, Louisiana 71130, United States.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Arnold
authors.affiliation: Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center , Shreveport, Louisiana 71130, United States.|Department of Pharmacology & Neuroscience, University of North Texas Health Science Center , Fort Worth, Texas 76107, United States.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Salvatore
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism*; D005080:Exercise Test; D005786:Gene Expression Regulation / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008124:Locomotion / Q000502:physiology; D008297:Male; D010805:Physical Conditioning, Animal / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D050580:Excitatory Amino Acid Transporter 3; C494989:Gfra1 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C493398:Slc1a1 protein, rat; D014316:Tritium; D018698:Glutamic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Aging; EAAC1; GFR-α1; exercise; substantia nigra; tyrosine hydroxylase