title: Reactive astrocytosis and glial glutamate transporter clustering are early changes in a spinocerebellar ataxia type 1 transgenic mouse model.
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.
authors.affiliation: Department of Surgical Sciences, University of Milano-Bicocca, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giovannoni
authors.forename: Nicola
authors.initials: N
authors.lastname: Maggio
authors.forename: Maria
authors.initials: M
authors.lastname: Rosaria Bianco
authors.forename: Carlo
authors.initials: C
authors.lastname: Cavaliere
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cirillo
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Lavitrano
authors.forename: Michele
authors.initials: M
authors.lastname: Papa