Dopamine D1-like receptors depress excitatory synaptic transmissions in striatal neurons after transient forebrain ischemia

Yuchun Zhang, Ping Deng, Yiwen Ruan, Zao C. Xu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE: Spiny neurons in the neostriatum are highly vulnerable to ischemia. Despite an enormous body of research suggesting that dopamine is involved in ischemia-induced neuronal loss in the striatum, it remains unclear how dopamine interacts with the glutamatergic excitotoxicity that is widely accepted as a major cause of ischemic cell death. Our study was designed to investigate the effects of dopamine D1 receptor (D1R) activation on excitatory neurotransmission in postischemic striatal neurons. METHODS: We used the 4-vessel occlusion ischemia model and brain slice preparations. Whole-cell voltage-clamp recording was performed on striatal neurons to measure excitatory postsynaptic currents (EPSCs). Systemic administration of a D1R agonist after ischemia and hematoxylin/eosin staining were performed to evaluate the effects of D1R activation on ischemia-induced neuronal degeneration in the striatum. RESULTS: D1R activation depressed EPSCs in postischemic striatal neurons. The depression was attributable to inhibition of presynaptic release. An activator of cAMP-dependent protein kinase A (PKA) mimicked the depressive effects of D1R activation. Bath application of a PKA inhibitor blocked the depression of EPSCs, whereas intracellular postsynaptic application of the PKA inhibitor had no effect. The D1R agonist failed to reduce EPSC amplitude in the presence of an adenosine A1 receptor antagonist. Systemic administration of a D1R agonist after ischemia significantly attenuated ischemia-induced cell death in the striatum. CONCLUSIONS: These results indicate that D1R activation presynaptically depresses excitatory synaptic transmission in striatal neurons after ischemia through activation of PKA and adenosine A1 receptors and thus demonstrate a novel mechanism of D1R-mediated protection against ischemia.

Original languageEnglish
Pages (from-to)2370-2376
Number of pages7
JournalStroke
Volume39
Issue number8
DOIs
StatePublished - Aug 1 2008

Fingerprint

Corpus Striatum
Dopamine D1 Receptors
Prosencephalon
Synaptic Transmission
Ischemia
Neurons
Cyclic AMP-Dependent Protein Kinases
Excitatory Postsynaptic Potentials
Protein Kinase Inhibitors
Dopamine
Cell Death
Adenosine A1 Receptor Antagonists
Neostriatum
Adenosine A1 Receptors
Hematoxylin
Eosine Yellowish-(YS)
Brain Ischemia
Baths
Staining and Labeling

Keywords

  • Adenosine
  • Dopamine
  • Excitatory postsynaptic currents
  • Ischemia
  • Striatum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Medicine(all)

Cite this

Dopamine D1-like receptors depress excitatory synaptic transmissions in striatal neurons after transient forebrain ischemia. / Zhang, Yuchun; Deng, Ping; Ruan, Yiwen; Xu, Zao C.

In: Stroke, Vol. 39, No. 8, 01.08.2008, p. 2370-2376.

Research output: Contribution to journalArticle

Zhang, Yuchun ; Deng, Ping ; Ruan, Yiwen ; Xu, Zao C. / Dopamine D1-like receptors depress excitatory synaptic transmissions in striatal neurons after transient forebrain ischemia. In: Stroke. 2008 ; Vol. 39, No. 8. pp. 2370-2376.
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