Altered long-term corticostriatal synaptic plasticity in transgenic mice overexpressing human CU/ZN superoxide dismutase (GLY(93)-->ALA) mutation
| Autoři: | Raffaella Geracitano, Giorgio Bernardi, Martine Ammassari-Teule, Nicola Berretta, S Prisco, Cristina Zona, Ezia Guatteo, N. B. Mercuri, Patrizia Longone, Egle Paolucci |
|---|---|
| Rok vydání: | 2003 |
| Témata: | amyotrophic lateral sclerosis, Patch-Clamp Techniques, animal diseases, striatum, Long-Term Potentiation, Action Potentials, Inbred C57BL, Transgenic, Mice, Neural Pathways, 5-Tetrahydro-7, 8-dihydroxy-1-phenyl-1H-3-benzazepine, Neurons, Alanine, Neuronal Plasticity, General Neuroscience, Dopaminergic, Long-term potentiation, Valine, SOD1, Dopamine Agonists, LTD, NMDA receptor, Settore MED/26 - Neurologia, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, LTP, medicine.drug, medicine.medical_specialty, Quinpirole, Genotype, Neurologic Mutants, Glycine, Substantia nigra, Mice, Transgenic, Biology, In Vitro Techniques, Motor Activity, Medium spiny neuron, Gyrus Cinguli, Settore BIO/09, Mice, Neurologic Mutants, Internal medicine, Dopaminergic Cell, medicine, Avoidance Learning, Animals, Humans, Superoxide Dismutase, Calcium, Disease Models, Animal, Electric Stimulation, Cell Membrane, Corpus Striatum, Mice, Inbred C57BL, Mutation, Animal, nutritional and metabolic diseases, nervous system diseases, Endocrinology, nervous system, Synaptic plasticity, Disease Models, amyotrophic lateral sclerosis, LTD, LTP, striatum, SOD1, Neuroscience |
| Popis: | Apart from the extensive loss of motor neurons, degeneration of midbrain dopaminergic cells has been described in both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Mice overexpressing the mutant human Cu/Zn superoxide dismutase (SOD1) show an ALS-like phenotype in that they show a progressive death of motor neurons accompanied by degeneration of dopaminergic cells. To describe the functional alterations specifically associated with this dopaminergic dysfunction, we have investigated the corticostriatal synaptic plasticity in mice overexpressing the human SOD1 (SOD1+) and the mutated (Gly(93)-->Ala) form (G93A+) of the same enzyme. We show that repetitive stimulation of the corticostriatal pathway generates long-term depression (LTD) in SOD1+ mice and in control (G93A-/SOD1-) animals, whereas in G93A+ mice the same stimulation generates an N-methyl-D-aspartic acid receptor-dependent long-term potentiation. No significant alterations were found in the intrinsic membrane properties of striatal medium spiny neurons and basal corticostriatal synaptic transmission of G93A+ mice. Bath perfusion of dopamine or the D(2) dopamine receptor agonist quinpirole restored LTD in G93A+ mice. Consistent with these in vitro results, habituation of locomotor activity and striatal-dependent active avoidance learning were impaired in G93A+ mice. Thus, degeneration of dopaminergic neurons in the substantia nigra of G93A+ mice causes substantial modifications in striatal synaptic plasticity and related behaviors, and may be a cellular substrate of the extrapyramidal motor and cognitive disorders observed in familial and sporadic ALS. |
| Jazyk: | English |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::43a68a0b97bc836562443d19211ac901 http://hdl.handle.net/2108/54439 |
| Rights: | CLOSED |
| Přírůstkové číslo: | edsair.doi.dedup.....43a68a0b97bc836562443d19211ac901 |
| Autor: | Raffaella Geracitano, Giorgio Bernardi, Martine Ammassari-Teule, Nicola Berretta, S Prisco, Cristina Zona, Ezia Guatteo, N. B. Mercuri, Patrizia Longone, Egle Paolucci |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
amyotrophic lateral sclerosis
Patch-Clamp Techniques animal diseases striatum Long-Term Potentiation Action Potentials Inbred C57BL Transgenic Mice Neural Pathways 5-Tetrahydro-7 8-dihydroxy-1-phenyl-1H-3-benzazepine Neurons Alanine Neuronal Plasticity General Neuroscience Dopaminergic Long-term potentiation Valine SOD1 Dopamine Agonists LTD NMDA receptor Settore MED/26 - Neurologia 2 3 4 5-Tetrahydro-7 8-dihydroxy-1-phenyl-1H-3-benzazepine LTP medicine.drug medicine.medical_specialty Quinpirole Genotype Neurologic Mutants Glycine Substantia nigra Mice Transgenic Biology In Vitro Techniques Motor Activity Medium spiny neuron Gyrus Cinguli Settore BIO/09 Mice Neurologic Mutants Internal medicine Dopaminergic Cell medicine Avoidance Learning Animals Humans Superoxide Dismutase Calcium Disease Models Animal Electric Stimulation Cell Membrane Corpus Striatum Mice Inbred C57BL Mutation Animal nutritional and metabolic diseases nervous system diseases Endocrinology nervous system Synaptic plasticity Disease Models amyotrophic lateral sclerosis LTD LTP striatum SOD1 Neuroscience |
| Popis: | Apart from the extensive loss of motor neurons, degeneration of midbrain dopaminergic cells has been described in both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Mice overexpressing the mutant human Cu/Zn superoxide dismutase (SOD1) show an ALS-like phenotype in that they show a progressive death of motor neurons accompanied by degeneration of dopaminergic cells. To describe the functional alterations specifically associated with this dopaminergic dysfunction, we have investigated the corticostriatal synaptic plasticity in mice overexpressing the human SOD1 (SOD1+) and the mutated (Gly(93)-->Ala) form (G93A+) of the same enzyme. We show that repetitive stimulation of the corticostriatal pathway generates long-term depression (LTD) in SOD1+ mice and in control (G93A-/SOD1-) animals, whereas in G93A+ mice the same stimulation generates an N-methyl-D-aspartic acid receptor-dependent long-term potentiation. No significant alterations were found in the intrinsic membrane properties of striatal medium spiny neurons and basal corticostriatal synaptic transmission of G93A+ mice. Bath perfusion of dopamine or the D(2) dopamine receptor agonist quinpirole restored LTD in G93A+ mice. Consistent with these in vitro results, habituation of locomotor activity and striatal-dependent active avoidance learning were impaired in G93A+ mice. Thus, degeneration of dopaminergic neurons in the substantia nigra of G93A+ mice causes substantial modifications in striatal synaptic plasticity and related behaviors, and may be a cellular substrate of the extrapyramidal motor and cognitive disorders observed in familial and sporadic ALS. |
| Databáze: | OpenAIRE |
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