Abstract
Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeats within the coding sequence of the ataxin-1 protein. In the present study, we used a conditional transgenic mouse model of SCA1 to investigate very early molecular and morphological changes related to the behavioral phenotype. In mice with neural deficits detected by rotarod performance, and simultaneous spatial impairments in exploratory activity and uncoordinated gait, we observed both significant altered expression and patchy distribution of excitatory amino acids transporter 1. The molecular changes observed in astroglial compartments correlate with changes in synapse morphology; synapses have a dramatic reduction of the synaptic area external to the postsynaptic density. By contrast, Purkinje cells demonstrate preserved structure. In addition, severe reactive astrocytosis matches changes in the glial glutamate transporter and synapse morphology. We propose these morpho-molecular changes are the cause of altered synaptic transmission, which, in turn, determines the onset of the neurological symptoms by altering the synaptic transmission in the cerebellar cortex of transgenic animals. This model might be suitable for testing drugs that target activated glial cells in order to reduce CNS inflammation.
| Original language | English |
|---|---|
| Pages (from-to) | 335-351 |
| Number of pages | 17 |
| Journal | Neuron Glia Biology |
| Volume | 3 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Nov 2007 |
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Keywords
- EAAT1
- Neurodegeneration
- SCA1
- Synaptic plasticity
ASJC Scopus subject areas
- Cell Biology
- Cellular and Molecular Neuroscience
Cite this
Reactive astrocytosis and glial glutamate transporter clustering are early changes in a spinocerebellar ataxia type 1 transgenic mouse model. / Giovannoni, Roberto; Maggio, Nicola; Rosaria Bianco, Maria; Cavaliere, Carlo; Cirillo, Giovanni; Lavitrano, Marialuisa; Papa, Michele.
In: Neuron Glia Biology, Vol. 3, No. 4, 11.2007, p. 335-351.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reactive astrocytosis and glial glutamate transporter clustering are early changes in a spinocerebellar ataxia type 1 transgenic mouse model
AU - Giovannoni, Roberto
AU - Maggio, Nicola
AU - Rosaria Bianco, Maria
AU - Cavaliere, Carlo
AU - Cirillo, Giovanni
AU - Lavitrano, Marialuisa
AU - Papa, Michele
PY - 2007/11
Y1 - 2007/11
N2 - Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeats within the coding sequence of the ataxin-1 protein. In the present study, we used a conditional transgenic mouse model of SCA1 to investigate very early molecular and morphological changes related to the behavioral phenotype. In mice with neural deficits detected by rotarod performance, and simultaneous spatial impairments in exploratory activity and uncoordinated gait, we observed both significant altered expression and patchy distribution of excitatory amino acids transporter 1. The molecular changes observed in astroglial compartments correlate with changes in synapse morphology; synapses have a dramatic reduction of the synaptic area external to the postsynaptic density. By contrast, Purkinje cells demonstrate preserved structure. In addition, severe reactive astrocytosis matches changes in the glial glutamate transporter and synapse morphology. We propose these morpho-molecular changes are the cause of altered synaptic transmission, which, in turn, determines the onset of the neurological symptoms by altering the synaptic transmission in the cerebellar cortex of transgenic animals. This model might be suitable for testing drugs that target activated glial cells in order to reduce CNS inflammation.
AB - Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeats within the coding sequence of the ataxin-1 protein. In the present study, we used a conditional transgenic mouse model of SCA1 to investigate very early molecular and morphological changes related to the behavioral phenotype. In mice with neural deficits detected by rotarod performance, and simultaneous spatial impairments in exploratory activity and uncoordinated gait, we observed both significant altered expression and patchy distribution of excitatory amino acids transporter 1. The molecular changes observed in astroglial compartments correlate with changes in synapse morphology; synapses have a dramatic reduction of the synaptic area external to the postsynaptic density. By contrast, Purkinje cells demonstrate preserved structure. In addition, severe reactive astrocytosis matches changes in the glial glutamate transporter and synapse morphology. We propose these morpho-molecular changes are the cause of altered synaptic transmission, which, in turn, determines the onset of the neurological symptoms by altering the synaptic transmission in the cerebellar cortex of transgenic animals. This model might be suitable for testing drugs that target activated glial cells in order to reduce CNS inflammation.
KW - EAAT1
KW - Neurodegeneration
KW - SCA1
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=46749137502&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=46749137502&partnerID=8YFLogxK
U2 - 10.1017/S1740925X08000185
DO - 10.1017/S1740925X08000185
M3 - Article
C2 - 18634565
AN - SCOPUS:46749137502
VL - 3
SP - 335
EP - 351
JO - Neuron Glia Biology
JF - Neuron Glia Biology
SN - 1740-925X
IS - 4
ER -