Abstract
There are many evidences implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). This neurodegenerative disorder is characterized by the progressive loss of motor neurons, whose pathogenesis is thought to involve Ca2+ influx mediated by α-amino-3-hydroxy-5-methyl-isoxazole-4- propionate receptors (AMPARs). In the present study we report alterations in the AMPARs function in a transgenic mouse-model of the human SOD1 G93A familial ALS. Compared with those expressed in motor neurons carrying the human wild type gene, AMPAR-gated channels expressed in motor neurons carrying the human mutant gene exhibited modified permeability, altered agonist cooperativity between the sites involved in the process of channel opening and were responsible for slower spontaneous synaptic events. These observations demonstrate that the SOD1G93A mutation induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS.
| Original language | English |
|---|---|
| Pages (from-to) | 47-58 |
| Number of pages | 12 |
| Journal | Neuroscience |
| Volume | 122 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Nov 20 2003 |
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Keywords
- ALS
- Excitotoxicity
- Glutamate receptors
- Patch-clamp
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors in spinal cord motor neurons are altered in transgenic mice overexpressing human Cu,Zn superoxide dismutase (Gly93→Ala) mutation. / Pieri, M.; Gaetti, C.; Spalloni, A.; Cavalcanti, S.; Mercuri, N.; Bernardi, G.; Longone, P.; Zona, C.
In: Neuroscience, Vol. 122, No. 1, 20.11.2003, p. 47-58.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors in spinal cord motor neurons are altered in transgenic mice overexpressing human Cu,Zn superoxide dismutase (Gly93→Ala) mutation
AU - Pieri, M.
AU - Gaetti, C.
AU - Spalloni, A.
AU - Cavalcanti, S.
AU - Mercuri, N.
AU - Bernardi, G.
AU - Longone, P.
AU - Zona, C.
PY - 2003/11/20
Y1 - 2003/11/20
N2 - There are many evidences implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). This neurodegenerative disorder is characterized by the progressive loss of motor neurons, whose pathogenesis is thought to involve Ca2+ influx mediated by α-amino-3-hydroxy-5-methyl-isoxazole-4- propionate receptors (AMPARs). In the present study we report alterations in the AMPARs function in a transgenic mouse-model of the human SOD1 G93A familial ALS. Compared with those expressed in motor neurons carrying the human wild type gene, AMPAR-gated channels expressed in motor neurons carrying the human mutant gene exhibited modified permeability, altered agonist cooperativity between the sites involved in the process of channel opening and were responsible for slower spontaneous synaptic events. These observations demonstrate that the SOD1G93A mutation induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS.
AB - There are many evidences implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). This neurodegenerative disorder is characterized by the progressive loss of motor neurons, whose pathogenesis is thought to involve Ca2+ influx mediated by α-amino-3-hydroxy-5-methyl-isoxazole-4- propionate receptors (AMPARs). In the present study we report alterations in the AMPARs function in a transgenic mouse-model of the human SOD1 G93A familial ALS. Compared with those expressed in motor neurons carrying the human wild type gene, AMPAR-gated channels expressed in motor neurons carrying the human mutant gene exhibited modified permeability, altered agonist cooperativity between the sites involved in the process of channel opening and were responsible for slower spontaneous synaptic events. These observations demonstrate that the SOD1G93A mutation induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS.
KW - ALS
KW - Excitotoxicity
KW - Glutamate receptors
KW - Patch-clamp
UR - http://www.scopus.com/inward/record.url?scp=0142226957&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142226957&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2003.07.003
DO - 10.1016/j.neuroscience.2003.07.003
M3 - Article
C2 - 14596848
AN - SCOPUS:0142226957
VL - 122
SP - 47
EP - 58
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 1
ER -