Adenosine A2A receptor antagonism increases nNOS-immunoreactive neurons in the striatum of Huntington transgenic mice

S Cipriani; E Bizzoco; M Gianfriddo; A Melani; M G Vannucchi; F Pedata

doi:10.1016/j.expneurol.2008.05.015

Adenosine A2A receptor antagonism increases nNOS-immunoreactive neurons in the striatum of Huntington transgenic mice

Exp Neurol. 2008 Sep;213(1):163-70. doi: 10.1016/j.expneurol.2008.05.015. Epub 2008 Jun 30.

Authors

S Cipriani¹, E Bizzoco, M Gianfriddo, A Melani, M G Vannucchi, F Pedata

Affiliation

¹ Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy.

PMID: 18586241
DOI: 10.1016/j.expneurol.2008.05.015

Abstract

Medium spiny GABAergic projection neurons are progressively lost in Huntington's disease (HD), whereas there is preferential sparing of the few interneurons co-expressing NPY, somatostatin and neuronal nitric oxide synthase. We investigated the effect of the selective adenosine A(2A) receptor antagonist SCH58261 (0.01 mg/kg, acutely and chronically administered i.p.) on nNOS striatal expression and motor impairment in R6/2 transgenic mice in clearly symptomatic phase (10-11-week old). SCH58261 chronically administered increased the number of nNOS-immunoreactive neurons (nNOS-IR) in the striatum of R6/2 mice. No glial activation was detected in the striatum or cortex. SCH58261 also improved walking in the inclined plane test but not motor capability evaluated by the rotarod test. These findings demonstrate for the first time a role of adenosine A(2A) receptors in regulating nNOS expression in the striatum. We suggest that the protective effect of A(2A) antagonism in HD is related to the increase in striatal nNOS-IR neurons.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / metabolism
Adenosine A2 Receptor Antagonists
Animals
Corpus Striatum / drug effects
Corpus Striatum / metabolism*
Corpus Striatum / physiopathology
Cytoprotection / drug effects
Cytoprotection / physiology
Disease Models, Animal
Enzyme Activation / drug effects
Enzyme Activation / physiology
Huntington Disease / drug therapy*
Huntington Disease / metabolism*
Huntington Disease / physiopathology
Interneurons / drug effects
Interneurons / metabolism
Male
Mice
Mice, Transgenic
Neuroprotective Agents / pharmacology
Nitrergic Neurons / drug effects
Nitrergic Neurons / metabolism*
Nitric Oxide / biosynthesis
Nitric Oxide Synthase Type I / metabolism*
Pyrimidines / pharmacology
Receptor, Adenosine A2A / metabolism*
Triazoles / pharmacology
Up-Regulation / drug effects
Up-Regulation / physiology

Substances

5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
Adenosine A2 Receptor Antagonists
Neuroprotective Agents
Pyrimidines
Receptor, Adenosine A2A
Triazoles
Nitric Oxide
Nitric Oxide Synthase Type I
Adenosine