Document Detail

Ischemic-LTP in striatal spiny neurons of both direct and indirect pathway requires the activation of D1-like receptors and NO/soluble guanylate cyclase/cGMP transmission.
MedLine Citation:
PMID:  23149555     Owner:  NLM     Status:  MEDLINE    
Striatal medium-sized spiny neurons (MSNs) are highly vulnerable to ischemia. A brief ischemic insult, produced by oxygen and glucose deprivation (OGD), can induce ischemic long-term potentiation (i-LTP) of corticostriatal excitatory postsynaptic response. Since nitric oxide (NO) is involved in the pathophysiology of brain ischemia and the dopamine D1/D5-receptors (D1-like-R) are expressed in striatal NOS-positive interneurons, we hypothesized a relation between NOS-positive interneurons and striatal i-LTP, involving D1R activation and NO production. We investigated the mechanisms involved in i-LTP induced by OGD in corticostriatal slices and found that the D1-like-R antagonist SCH-23390 prevented i-LTP in all recorded MSNs. Immunofluorescence analysis confirmed the induction of i-LTP in both substance P-positive, (putative D1R-expressing) and adenosine A2A-receptor-positive (putative D2R-expressing) MSNs. Furthermore, i-LTP was dependent on a NOS/cGMP pathway since pharmacological blockade of NOS, guanylate-cyclase, or PKG prevented i-LTP. However, these compounds failed to prevent i-LTP in the presence of a NO donor or cGMP analog, respectively. Interestingly, the D1-like-R antagonism failed to prevent i-LTP when intracellular cGMP was pharmacologically increased. We propose that NO, produced by striatal NOS-positive interneurons via the stimulation of D1-like-R located on these cells, is critical for i-LTP induction in the entire population of MSNs involving a cGMP-dependent pathway.
Sara Arcangeli; Alessandro Tozzi; Michela Tantucci; Cristiano Spaccatini; Antonio de Iure; Cinzia Costa; Massimiliano Di Filippo; Barbara Picconi; Carmen Giampà; Francesca Romana Fusco; Salvatore Amoroso; Paolo Calabresi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-01     Completed Date:  2013-03-25     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  278-86     Citation Subset:  IM    
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MeSH Terms
Benzazepines / pharmacology
Brain Ischemia / metabolism*,  pathology,  physiopathology
Corpus Striatum / metabolism*,  physiopathology
Cyclic GMP / metabolism*
Glucose / metabolism
Guanylate Cyclase / metabolism*
Interneurons / metabolism*,  pathology
Long-Term Potentiation / drug effects
Nerve Tissue Proteins / metabolism*
Nitric Oxide / metabolism*
Nitric Oxide Donors / pharmacology
Oxygen / metabolism
Rats, Wistar
Receptor, Adenosine A2A / metabolism
Receptors, Dopamine D1 / antagonists & inhibitors,  metabolism*
Receptors, Dopamine D5 / antagonists & inhibitors,  metabolism
Synaptic Transmission*
Reg. No./Substance:
0/Benzazepines; 0/Nerve Tissue Proteins; 0/Nitric Oxide Donors; 0/Receptor, Adenosine A2A; 0/Receptors, Dopamine D1; 0/SCH 23390; 137750-35-7/Receptors, Dopamine D5; 31C4KY9ESH/Nitric Oxide; EC Cyclase; H2D2X058MU/Cyclic GMP; IY9XDZ35W2/Glucose; S88TT14065/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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