N-methyl-d-aspartate receptors are critical for mediating the effects of glutamate on intracellular calcium concentration and immediate early gene expression in cultured hippocampal neurons

Bading, Hilmar; Segal, Michael M.; Sucher, Nikolaus J.; Dudek, Henryk; Lipton, Stuart A.; Greenberg, Michael E.

doi:10.1016/0306-4522(94)00462-e

Cited by 152 publications

(94 citation statements)

References 35 publications

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“…In the initial phase of NMDA-overstimulation as in ischaemic conditions Ca 2ϩ influx depends primarily on NMDA-channels (Bading et al, 1995;Garcia et al, 1994). There are good arguments that secondary Ca 2ϩ currents through activated VDCC are involved in the later stages of NMDA-induced cell damage (Garcia et al, 1994;Lobner & Lipton, 1993).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Protection against NMDA-induced Neurodegeneration by MK-801 and Nimodipine: Combined Therapy and Temporal Course of Protection

et al. 1996

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Section: Discussionmentioning

confidence: 99%

In Vivo Protection against NMDA-induced Neurodegeneration by MK-801 and Nimodipine: Combined Therapy and Temporal Course of Protection

et al. 1996

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“…We observed, however, a small number of unstimulated neurons that express pFos⌬CREmyc at moderate and even high levels. Although this may be attributable to spontaneous electrical activation of the neurons, as described previously for the endogenous c-fos gene (Bading et al, 1995), it is also possible that the stress associated with microinjection of DNA constructs triggers a transcriptional response in some hippocampal neurons, giving rise to false-positive cells. In a fraction of the neurons (28%) expression of pFos⌬CREmyc was not induced after glutamate stimulation, which resembles results obtained previously with the endogenous c-fos gene (Bading et al, 1995) and may reflect a lack of f unctional NMDA receptors.…”

Section: Nmda Receptor Activation Can Mediate Transcriptional Inductimentioning

confidence: 96%

“…Although this may be attributable to spontaneous electrical activation of the neurons, as described previously for the endogenous c-fos gene (Bading et al, 1995), it is also possible that the stress associated with microinjection of DNA constructs triggers a transcriptional response in some hippocampal neurons, giving rise to false-positive cells. In a fraction of the neurons (28%) expression of pFos⌬CREmyc was not induced after glutamate stimulation, which resembles results obtained previously with the endogenous c-fos gene (Bading et al, 1995) and may reflect a lack of f unctional NMDA receptors. Glutamate regulation of pFos⌬CRE⌬TCFmyc was virtually identical to that of pFos⌬CREmyc, with most cells showing moderate or strong levels of induction and a fraction of neurons (27%) with no detectable transcriptional response.…”

Section: Nmda Receptor Activation Can Mediate Transcriptional Inductimentioning

confidence: 96%

“…Indeed, in PC12 cells in which the TCF-dependent mechanism targets the c-fos SRE, ␤-actin expression is not induced by KC l-induced membrane depolarization (Bartel et al, 1989). In contrast, in hippocampal neurons in which the c-fos SRE is activated by an SRF-linked mechanism, transcription of ␤-actin is stimulated by calcium signals (Bading et al, 1995). Thus, the cell type is an important determinant for the functional significance of a particular calcium-signaling pathway and provides a means for differential gene expression by calcium signals.…”

Section: The Sre Integrates Two Calcium-signaling Pathwaysmentioning

confidence: 99%

“…for transcriptional regulation by the excitatory neurotransmitter glutamate (Cole et al, 1989;Wisden et al, 1990;Lerea et al, 1992;Bading et al, 1993Bading et al, , 1995Lerea and McNamara, 1993). A previous study has shown that the c-fos SRE can f unction as an NMDA receptor-responsive element (Bading et al, 1993).…”

Section: Nmda Receptor Activation Can Mediate Transcriptional Inductimentioning

confidence: 99%

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Calcium Controls Gene Expression via Three Distinct Pathways That Can Function Independently of the Ras/Mitogen-Activated Protein Kinases (ERKs) Signaling Cascade

et al. 1997

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Calcium ions are the principal second messenger in the control of gene expression by electrical activation of neurons. However, the full complexity of calcium-signaling pathways leading to transcriptional activation and the cellular machinery involved are not known. Using the c-fos gene as a model system, we show here that the activity of its complex promoter is controlled by three independently operating signaling mechanisms and that their functional significance is cell type-dependent. The serum response element (SRE), which is composed of a ternary complex factor (TCF) and a serum response factor (SRF) binding site, integrates two calcium-signaling pathways. In PC12 cells, calcium-regulated transcription mediated by the SRE requires the TCF site and is not inhibited by expression of the dominant-negative Ras mutant, RasN17, nor by the MAP kinase kinase 1 inhibitor PD 98059. In contrast, TCF-dependent transcriptional regulation by nerve growth factor or epidermal growth factor is mediated by a Ras/MAP kinases (ERKs) pathway targeting the TCF Elk-1. In AtT20 cells and hippocampal neurons, calcium signals can stimulate transcription via a TCFindependent mechanism that requires the SRF binding site. The cyclic AMP response element (CRE), which cooperates with the TCF site in growth factor-regulated transcription, is a target of a third calcium-regulated pathway that is little affected by the expression of RasN17 or by PD 98059. Thus, calcium can stimulate gene expression via a TCF-, SRF-, and CRE-linked pathway that can operate independently of the Ras/MAP kinases (ERKs) signaling cascade in a cell type-dependent manner.

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Ultrastructural localization of sorcin, a 22 kDa calcium binding protein, in the rat caudate-putamen nucleus: Association with ryanodine receptors and intracellular calcium release

1997

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Sorcin is a 22 kDa calcium binding protein that is widely distributed in mammalian tissues, including brain, and is associated with the ryanodine receptor (RyR) family of intracellular calcium-release channels in the heart. To determine the cellular sites for potential central functions of sorcin, we examined the electron microscopic immunocytochemical localization of antipeptide antisera against sorcin and against cardiac and brain RyR in the rat caudate-putamen nucleus (CPN), one of the few regions expressing high levels of brain RyR. Sorcin-like immunoreactivity (S-LI) was detected in both neurons and glia by using immunoperoxidase and immunogold methods. Of 1,735 profiles containing immunogold-silver labeling for sorcin, almost 50% were dendrites and many of these dendrites were spiny. The remainder were mainly small axons, axon terminals, and, more rarely, glia. Furthermore, analysis of dually labeled tissue sections showed the presence of sorcin in many of the dendrites and some of the axonal and glial processes containing RyR. In dendrites, gold-silver deposits showing S-LI were prominently localized to saccules of smooth endoplasmic reticulum and mitochondria, both of which are known to store calcium. These labeled structures were located near the plasma membrane at sites postsynaptic to excitatory-type asymmetric junctions, as well as non-synaptic portions of the plasma membrane. In axons, S-LI was also often seen at extrasynaptic sites on, or near, the plasma membrane. We conclude that in the rat CPN, sorcin may act independently or, in conjunction with RyR, to modulate cytoplasmic release of calcium, mainly from smooth endoplasmic reticulum and/or mitochondria in neurons.

show abstract

N-methyl-d-aspartate receptors are critical for mediating the effects of glutamate on intracellular calcium concentration and immediate early gene expression in cultured hippocampal neurons

Cited by 152 publications

References 35 publications

In Vivo Protection against NMDA-induced Neurodegeneration by MK-801 and Nimodipine: Combined Therapy and Temporal Course of Protection

In Vivo Protection against NMDA-induced Neurodegeneration by MK-801 and Nimodipine: Combined Therapy and Temporal Course of Protection

Calcium Controls Gene Expression via Three Distinct Pathways That Can Function Independently of the Ras/Mitogen-Activated Protein Kinases (ERKs) Signaling Cascade

Ultrastructural localization of sorcin, a 22 kDa calcium binding protein, in the rat caudate-putamen nucleus: Association with ryanodine receptors and intracellular calcium release

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