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.
| Original language | English |
|---|---|
| Pages (from-to) | 235-243 |
| Number of pages | 9 |
| Journal | Purinergic Signalling |
| Volume | 14 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Sep 1 2018 |
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Keywords
- 3-Nitropropionic acid
- Adenosine A receptors
- Huntington’s disease
- Striatum
- Synaptic transmission
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology
Cite this
Neuronal adenosine A 2A receptor overexpression is neuroprotective towards 3-nitropropionic acid-induced striatal toxicity : a rat model of Huntington’s disease. / Domenici, Maria Rosaria; Chiodi, Valentina; Averna, Mirko; Armida, Monica; Pèzzola, Antonella; Pepponi, Rita; Ferrante, Antonella; Bader, Michael; Fuxe, Kjell; Popoli, Patrizia.
In: Purinergic Signalling, Vol. 14, No. 3, 01.09.2018, p. 235-243.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=85047106475&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047106475&partnerID=8YFLogxK
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 -