ArticleProceedings of the National Academy of Sciences of the United States of America1995
Glutamate as a hippocampal neuron survival factor: an inherited defect in the trisomy 16 mouse.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 78 citations in OpenAlex.
- Dose-Dependent Modulation of NMDA Receptors: Neuroprotective Mechanisms against Oxidative Stress in Hippocampal Neurons.International journal of molecular and cellular medicine · 2025Article
- In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia.Biomolecules · 2020Review
- Application of the amniotic fluid metabolome to the study of fetal malformations, using Down syndrome as a specific model.Molecular medicine reports · 2017Article
- Botanical Drug Puerarin Attenuates 6-Hydroxydopamine (6-OHDA)-Induced Neurotoxicity via Upregulating Mitochondrial Enzyme Arginase-2.Molecular neurobiology · 2016Article
- An L-type calcium channel agonist, bay K8644, extends the window of intervention against ischemic neuronal injury.Molecular neurobiology · 2013Article
- DRUG FOCUS: S 18986: A positive allosteric modulator of AMPA-type glutamate receptors pharmacological profile of a novel cognitive enhancer.CNS neuroscience & therapeutics · 2010Article
- Coupling of the NMDA receptor to neuroprotective and neurodestructive events.Biochemical Society transactions · 2009Review
- Riluzole in the treatment of mood and anxiety disorders.CNS drugs · 2008Review
- In vitro and in vivo analysis of neurotrophin-3 activation of Arf6 and Rac-1.Methods in enzymology · 2008Article
- Glutamate antagonists are neurotoxins for the developing brain.Neurotoxicity research · 2007Review
- Biphasic coupling of neuronal nitric oxide synthase phosphorylation to the NMDA receptor regulates AMPA receptor trafficking and neuronal cell death.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007Article
- Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2006Article
- Dual modulation of endocannabinoid transport and fatty acid amide hydrolase protects against excitotoxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2005Article
- Neurotrophic effects of AMPA.Cerebellum (London, England) · 2004Review
- Failure of brain-derived neurotrophic factor-dependent neuron survival in mouse trisomy 16.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2002Article
- Role of founder cell deficit and delayed neuronogenesis in microencephaly of the trisomy 16 mouse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000Article
- Altered Ca2+ signaling and mitochondrial deficiencies in hippocampal neurons of trisomy 16 mice: a model of Down's syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1998Article
- Isoform-specific regulation of the Na+/Ca2+ exchanger in rat astrocytes and neurons by PKA.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1998Article
- Consequences of trisomy 16 for mouse brain development: corticogenesis in a model of Down syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1996Article
- Behavioral and neurochemical recovery from partial 6-hydroxydopamine lesions of the substantia nigra is blocked by daily treatment with glutamate receptor antagonists MK-801 and CPP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1996Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The survival of cultured mouse hippocampal neurons was found to be greatly enhanced by micromolar concentrations of the excitatory neurotransmitter glutamate. Blockade of kainate/AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) glutamate receptors increased the rate of neuron death, suggesting that endogenous glutamate in the cultures promotes survival. Addition of glutamate (0.5-1 microM) further increased neuron survival, whereas glutamate in excess of 20 microM resulted in increased death. Thus, the survival vs. glutamate dose-response relation is bell-shaped with an optimal glutamate concentration near 1 microM. We found that 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. In contrast, the neurotrophic polypeptide basic fibroblast growth factor did increase the survival of Ts16 and euploid neurons. Ts16 is a naturally occurring mouse genetic abnormality, the human analog of which (Down syndrome) leads to altered brain development and Alzheimer 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 contribute to their accelerated death.
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