Amyloid-β1–42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1
Journal of Neuroscience, 2013•Soc Neuroscience
GLT-1, the major glutamate transporter in the adult brain, is abundantly expressed in
astrocytic processes enveloping synapses. By limiting glutamate escape into the
surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we
show that the amyloid-β peptide Aβ1–42 markedly prolongs the extracellular lifetime of
synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes
and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate …
astrocytic processes enveloping synapses. By limiting glutamate escape into the
surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we
show that the amyloid-β peptide Aβ1–42 markedly prolongs the extracellular lifetime of
synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes
and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate …
GLT-1, the major glutamate transporter in the adult brain, is abundantly expressed in astrocytic processes enveloping synapses. By limiting glutamate escape into the surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we show that the amyloid-β peptide Aβ1–42 markedly prolongs the extracellular lifetime of synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate that astrocytic glutamate transporter dysfunction may play an important role in the pathogenesis of Alzheimer's disease and suggest possible mechanisms by which several current treatment strategies could protect against the disease.
Soc Neuroscience