Glutamate-Promoted Survival in Hippocampal Neurons: A Defect in Mouse Trisomy 16
Micromolar concentrations of glutamate, acting at non-NMDA, kainate-preferring receptors, increased the survival of cultured mouse hippocampal neurons maintained in serum-free, chemically-defined medium. Glutamate in excess of 20 μM was excitotoxic. Thus, the survival versus glutamate dose response relation was bell-shaped with an optimal glutamate concentration near 1 μM. Hippocampal neurons from mice with the genetic defect, trisomy 16 (Ts16), died 2–3 times faster than normal (euploid) neurons. Moreover, glutamate, at all concentrations tested, failed to increase survival of Ts16 neurons. Ts16 is a naturally-occurring mouse genetic abnormality, the human analog of which (Down syndrome) leads to altered brain development and Alzheimer’s disease. These results demonstrate that the Ts16 genotype confers a defect in the glutamate-mediated survival response of hippocampal neurons and that this defect can account for their accelerated death.
KeywordsDown Syndrome Hippocampal Neuron Basal Forebrain Cerebellar Granule Cell Basal Forebrain Cholinergic Neuron
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