TY - JOUR
T1 - Neuronal adenosine A
2A
receptor overexpression is neuroprotective towards 3-nitropropionic acid-induced striatal toxicity
T2 - a rat model of Huntington’s disease
AU - Domenici, Maria Rosaria
AU - Chiodi, Valentina
AU - Averna, Mirko
AU - Armida, Monica
AU - Pèzzola, Antonella
AU - Pepponi, Rita
AU - Ferrante, Antonella
AU - Bader, Michael
AU - Fuxe, Kjell
AU - Popoli, Patrizia
PY - 2018/9/1
Y1 - 2018/9/1
N2 -
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.
AB -
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.
KW - 3-Nitropropionic acid
KW - Adenosine A receptors
KW - Huntington’s disease
KW - Striatum
KW - Synaptic transmission
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U2 - 10.1007/s11302-018-9609-4
DO - 10.1007/s11302-018-9609-4
M3 - Article
C2 - 29770921
AN - SCOPUS:85047106475
VL - 14
SP - 235
EP - 243
JO - Purinergic Signalling
JF - Purinergic Signalling
SN - 1573-9538
IS - 3
ER -