Bilateral effects of unilateral GDNF administration on dopamine- and GABA-regulating proteins in the rat nigrostriatal system

Michael Francis Salvatore, Greg A. Gerhardt, Robert D. Dayton, Ronald L. Klein, John A. Stanford

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24 Citations (Scopus)

Abstract

Dopamine (DA) affects GABA neuronal function in the striatum and together these neurotransmitters play a large role in locomotor function. We recently reported that unilateral striatal administration of GDNF, a growth factor that has neurotrophic effects on DA neurons and enhances DA release, bilaterally increased striatal neuron activity related to locomotion in aged rats. We hypothesized that the GDNF enhancement of DA function and resulting bilateral enhancement of striatal neuronal activity was due to prolonged bilateral changes in DA- and GABA-regulating proteins. Therefore in these studies we assessed dopamine- and GABA-regulating proteins in the striatum and substantia nigra (SN) of 24 month old Fischer 344 rats, 30 days after a single unilateral striatal delivery of GDNF. The nigrostriatal proteins investigated were the DA transporter (DAT), tyrosine hydroxylase (TH), and TH phosphorylation and were examined by blot-immunolabeling. The striatal GABA neuron-related proteins were examined by assay of the DA D 1 receptor, DARPP-32, DARPP-32 Thr 34 phosphorylation, and glutamic acid decarboxylase (GAD). Bilateral effects of GDNF on TH and DAT occurred only in the SN, as 30 μg GDNF increased ser19 phosphorylation, and 100 μg GDNF decreased DAT and TH protein levels. GDNF also produced bilateral changes in GAD protein in the striatum. A decrease in DARPP-32 occurred in the ipsilateral striatum, while increased D 1 receptor and DARPP-32 phosphorylation occurred in the contralateral striatum. The 30 μg GDNF infusion into the lateral striatum was confined to the ipsilateral striatum and substantia nigra. Thus, long-lasting bilateral effects of GDNF on proteins regulating DA and GABA neuronal function likely alter physiological properties in neurons, some with bilateral projections, associated with locomotion. Enhanced nigrostriatal excitability and DA release by GDNF may trigger these bilateral effects.

Original languageEnglish
Pages (from-to)197-207
Number of pages11
JournalExperimental Neurology
Volume219
Issue number1
DOIs
StatePublished - 1 Sep 2009

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Glial Cell Line-Derived Neurotrophic Factor
gamma-Aminobutyric Acid
Dopamine
Corpus Striatum
Tyrosine 3-Monooxygenase
Proteins
Substantia Nigra
Phosphorylation
Glutamate Decarboxylase
Locomotion
Neurons
GABAergic Neurons
Dopamine Plasma Membrane Transport Proteins
Dopaminergic Neurons
Inbred F344 Rats
Neurotransmitter Agents

Keywords

  • Bilateral
  • DARPP-32
  • Dopamine transporter
  • GDNF
  • Glutamic acid decarboxylase (GAD)
  • Nigrostriatal
  • Striatonigral
  • Trophic factor
  • Tyrosine hydroxylase

Cite this

Salvatore, Michael Francis ; Gerhardt, Greg A. ; Dayton, Robert D. ; Klein, Ronald L. ; Stanford, John A. / Bilateral effects of unilateral GDNF administration on dopamine- and GABA-regulating proteins in the rat nigrostriatal system. In: Experimental Neurology. 2009 ; Vol. 219, No. 1. pp. 197-207.
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Bilateral effects of unilateral GDNF administration on dopamine- and GABA-regulating proteins in the rat nigrostriatal system. / Salvatore, Michael Francis; Gerhardt, Greg A.; Dayton, Robert D.; Klein, Ronald L.; Stanford, John A.

In: Experimental Neurology, Vol. 219, No. 1, 01.09.2009, p. 197-207.

Research output: Contribution to journalArticleResearchpeer-review

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