Striatal glutamate degenerates thalamic neurons.

Glutamate (GLU)-induced excitotoxicity is considered to be a frequent cause of cell degeneration in basal ganglia disorders; it is normally prevented by uptake of GLU by astrocytes. We recently found that transient perfusion of GLU in the striatum induces persistent accumulation of GLU in striatal astrocytes that could be from the initial administration or caused by the slow release from neurons or astrocytes in response to it. Endogenous production of GLU, that is, "self-induced GLU accumulation" (SIGA), may occur under physiological and pathological conditions. Here we studied the possible induction of SIGA after injury induced by perfusion of GLU receptor agonists into the striatum of rats. The agonists induced local degeneration in neurons and myelinated axons and microgliosis and astrocytosis; there was also gliosis and remote degeneration of neurons in the ventral-posterior complex of the thalamus that project to the cerebral cortex across the striatum. Reactive astrocytes showed persistent GLU accumulation in the striatum (local SIGA) and thalamus (remote SIGA) that persisted for at least 6 weeks after the injury. Thus, SIGA can be induced by neuronal degeneration retrogradely triggered from a remote brain region after excessive release of endogenous GLU from astrocytes. This may be an additional factor to be considered in basal ganglia disorders with glutamatergic excitotoxicity.