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Neuronal adenosine A(2A) receptor overexpression is neuroprotective towards 3-nitropropionic acid-induced striatal toxicity: a rat model of Huntington's disease

Item Type:Article
Title:Neuronal adenosine A(2A) receptor overexpression is neuroprotective towards 3-nitropropionic acid-induced striatal toxicity: a rat model of Huntington's disease
Creators Name:Domenici, M.R. and Chiodi, V. and Averna, M. and Armida, M. and Pèzzola, A. and Pepponi, R. and Ferrante, A. and Bader, M. and Fuxe, K. and Popoli, P.
Abstract:The A(2A) adenosine receptor (A(2A)R) is widely distributed on different cellular types in the brain, where it exerts a broad spectrum of pathophysiological functions, and for which a role in different neurodegenerative diseases has been hypothesized or demonstrated. To investigate the role of neuronal A(2A)Rs in neurodegeneration, we evaluated in vitro and in vivo the effect of the neurotoxin 3-nitropropionic acid (3-NP) in a transgenic rat strain overexpressing A(2A)Rs under the control of the neural-specific enolase promoter (NSEA(2A) rats). We recorded extracellular field potentials (FP) in corticostriatal slice and found that the synaptotoxic effect of 3-NP was significantly reduced in NSEA(2A) rats compared with wild-type animals (WT). In addition, after exposing corticostriatal slices to 3-NP 10 mM for 2 h, we found that striatal cell viability was significantly higher in NSEA(2A) rats compared to control rats. These in vitro results were confirmed by in vivo experiments: daily treatment of female rats with 3-NP 10 mg/kg for 8 days induced a selective bilateral lesion in the striatum, which was significantly reduced in NSEA(2A) compared to WT rats. These results demonstrate that the overexpression of the A(2A)R selectively at the neuronal level reduced 3-NP-induced neurodegeneration, and suggest an important function of the neuronal A(2A)R in the modulation of neurodegeneration.
Keywords:Adenosine A(2A) Receptors, Huntington's Disease, 3-Nitropropionic Acid, Synaptic Transmission, Striatum, Animals, Rats
Source:Purinergic Signalling
ISSN:1573-9538
Publisher:Springer (The Netherlands)
Volume:14
Number:3
Page Range:235-243
Date:September 2018
Official Publication:https://doi.org/10.1007/s11302-018-9609-4
PubMed:View item in PubMed

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