Control of glutamate transmission in neurological disorders : regulation of glutamate transporter splice variants and the associated protein PICK1

(eng) In the glutamatergic synapse, the efficient uptake ensured by the glial glutamate transporter GLT-1 represents the principal mechanism that limits the amplitude and duration of the excitatory transmission. In this study, we have demonstrated that alternative splice variants of GLT-1 (GLT-1a and GLT-1b) are differentially expressed in cultured astrocytes exposed to a pro-inflammatory environment. Moreover, the GLT-1b associated protein, PICK1, is induced in activated astrocytes from the spinal cord of animals suffering from a motor neuron disease, amyotrophic lateral sclerosis. Altogether, the data presented in this thesis indicate that the neuroinflammatory-induced activation of astrocytes, a feature of many neurological disorders, may be correlated with alterations of glutamate uptake through the differential expression of GLT-1 splice variants and the associated protein PICK1.