Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures

Kristensen, Bjarne Winther; Noraberg, Jens; Jakobsen, Birthe; Gramsbergen, Jan Bert; Ebert, Bjarke; Zimmer, Jens

doi:10.1016/s0006-8993(99)01833-8

Cited by 48 publications

(31 citation statements)

References 64 publications

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“…As previously reported, the toxicity induced by 6 µM kainate followed a different pattern from that observed in the presence of 2 µM AMPA (26,35). Exposure of hippocampal slice cultures to 6 µM kainate for 24 h induced PtdIns uptake in the CA1 (122.6±12.8% of control, n=33) and in particular in the CA3 (161.4±12.7% of control, n=33) pyramidal cell layer, whereas no increase PtdIns uptake was found in the dentate granule cell layer (105.1±4.4%, n=33) (Figs.…”

Section: Protection Against Kainic Acid-induced Neurodegeneration Of mentioning

confidence: 45%

Activation of neuropeptide Y receptors is neuroprotective against excitotoxicity in organotypic hippocampal slice cultures

et al. 2003

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Glutamate and NPY have been implicated in hippocampal neuropathology in temporal lobe epilepsy. Thus, we investigated the involvement of NPY receptors in mediating neuroprotection against excitotoxic insults in organotypic cultures of rat hippocampal slices. Exposure of hippocampal slice cultures to 2 µM AMPA (α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate) induced neuronal degeneration, monitored by propidium iodide uptake, of granule cells and CA1 pyramidal cells. For AMPA, whereas only the activation of Y2 receptors was effective for CA1 pyramidal cells. When the slice cultures were exposed to 6 µM kainate, the CA3 pyramidal cells displayed significant degeneration, and in this case the activation of Y1, Y2, and Y5 receptors was neuroprotective. For the kainic acid-induced degeneration of CA1 pyramidal cells, it was again found that only the Y2 receptor activation was effective. Based on the present findings, it was concluded that Y1, Y2, and Y5 receptors effectively can modify glutamate receptor-mediated neurodegeneration in the hippocampus.Key words: NPY • AMPA • kainate • neuroprotection • neurodegeneration N europeptide Y (NPY) is a 36-amino-acid peptide abundantly distributed in the brain and associated with a number of physiological and pathological conditions (1). This peptide has been shown to modulate anxiety, pain, memory, eating behavior, and many other functions in the central, as well as in the peripheral, nervous systems (1, 2). Another significant role of NPY that has become evident during the past decade is regulation of seizure activity (3).At least five NPY receptor subtypes have been identified based on different pharmacological profiles: Y1, Y2, Y4, Y5, and y6 (4). A putative Y3 receptor has also been identified (5 In the hippocampus, Y1 and Y2 receptors are highly expressed (11). Receptors of the Y1 subtype are preferentially located in granule cells of the dentate molecular layer, whereas Y2 receptors are expressed at high concentrations in the mossy fiber and Schaffer collateral fields (12). Moreover, Y5 receptor binding sites can also be found in the strata oriens and radiatum of the CA3 and CA1 areas (13,14). Presently, there is evidence for the involvement of these three NPY receptors subtypes in epilepsy. The activation of Y2 receptors suppresses seizure activity in hippocampal slices in vitro (15) and in vivo models (3). In human temporal lobe epilepsy, significant alterations in Y1 and Y2 receptor binding were observed (16). NPY Y5 receptors also seem to be involved in the suppression of seizure activity (17,18). In different animal models of epilepsy, NPY is highly expressed by granule cells and mossy fibers of the hippocampus (19,20), whereas in normal conditions only GABAergic interneurons express this peptide. Furthermore, knockout mice lacking the NPY gene develop spontaneous seizures and are more susceptible to pentylenetetrazol and kainic acid-induced motor seizures, which are inhibited by intracerebral infusion of NPY (21). Thus, these evidences suggest that N...

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Section: Protection Against Kainic Acid-induced Neurodegeneration Of mentioning

confidence: 45%

Activation of neuropeptide Y receptors is neuroprotective against excitotoxicity in organotypic hippocampal slice cultures

et al. 2003

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“…In addition to FK stimulation, we tested the effects of kainic acid (KA) (50 M) stimulation on 6 IEGs (Fos, FosB, Egr1, Egr2, Arc, and Bdnf). KA is a glutamate agonist that binds specifically to the kainate receptor class of ionotropic glutamate receptors, which play important roles in synaptic plasticity (37,48). We found that 4 genes (Egr1, Egr2, Fosb, and Arc) were induced at higher rates in Satb1-null cortical culture, while Fos and Bdnf expression were similar to that in wild-type controls (see Fig.…”

Section: Satb1 Affects Inducibility Of Iegs and Other Neural Genes Inmentioning

confidence: 68%

Satb1 Ablation Alters Temporal Expression of Immediate Early Genes and Reduces Dendritic Spine Density during Postnatal Brain Development

Balamotis

Tamberg

Woo

et al. 2012

Molecular and Cellular Biology

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Complex behaviors, such as learning and memory, are associated with rapid changes in gene expression of neurons and subsequent formation of new synaptic connections. However, how external signals are processed to drive specific changes in gene expression is largely unknown. We found that the genome organizer protein Satb1 is highly expressed in mature neurons, primarily in the cerebral cortex, dentate hilus, and amygdala. In Satb1-null mice, cortical layer morphology was normal. However, in postnatal Satb1-null cortical pyramidal neurons, we found a substantial decrease in the density of dendritic spines, which play critical roles in synaptic transmission and plasticity. Further, we found that in the cerebral cortex, Satb1 binds to genomic loci of multiple immediate early genes (IEGs) (Fos, Fosb, Egr1, Egr2, Arc, and Bdnf) and other key neuronal genes, many of which have been implicated in synaptic plasticity. Loss of Satb1 resulted in greatly alters timing and expression levels of these IEGs during early postnatal cerebral cortical development and also upon stimulation in cortical organotypic cultures. These data indicate that Satb1 is required for proper temporal dynamics of IEG expression. Based on these findings, we propose that Satb1 plays a critical role in cortical neurons to facilitate neuronal plasticity.

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“…Hippocampal slice cultures were prepared from 6-to 8-d-old wild-type (WT) or TNFR KO C57BL/6 mice, according to the interface culture method (Stoppini et al, 1991), as modified by Kristensen et al (1999) and Noraberg et al (1999). C57BL/6 mice was the strain used to generate homozygous TNFR1…”

Section: Methodsmentioning

confidence: 99%

Modulator Effects of Interleukin-1β and Tumor Necrosis Factor-α on AMPA-Induced Excitotoxicity in Mouse Organotypic Hippocampal Slice Cultures

Bernardino¹,

Xapelli²,

Silva³

et al. 2005

J. Neurosci.

201

169

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The inflammatory cytokines interleukin-1␤ and tumor necrosis factor-␣ (TNF-␣) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects of these cytokines on neuronal death caused by exposure of mouse organotypic hippocampal slice cultures to toxic concentrations of AMPA. Either potentiation of excitotoxicity or neuroprotection was observed, depending on the concentration of the cytokines and the timing of exposure. A relatively high concentration of mouse recombinant TNF-␣ (10 ng/ml) enhanced excitotoxicity when the cultures were simultaneously exposed to AMPA and to this cytokine. Decreasing the concentration of TNF-␣ to 1 ng/ml resulted in neuroprotection against AMPA-induced neuronal death independently on the application protocol. By using TNF-␣ receptor (TNFR) knock-out mice, we demonstrated that the potentiation of AMPA-induced toxicity by TNF-␣ involves TNF receptor-1, whereas the neuroprotective effect is mediated by TNF receptor-2. AMPA exposure was associated with activation and proliferation of microglia as assessed by macrophage antigen-1 and bromodeoxyuridine immunohistochemistry, suggesting a functional recruitment of cytokineproducing cells at sites of neurodegeneration. Together, these findings are relevant for understanding the role of proinflammatory cytokines and microglia activation in acute and chronic excitotoxic conditions.

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Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures

Cited by 48 publications

References 64 publications

Activation of neuropeptide Y receptors is neuroprotective against excitotoxicity in organotypic hippocampal slice cultures

Activation of neuropeptide Y receptors is neuroprotective against excitotoxicity in organotypic hippocampal slice cultures

Satb1 Ablation Alters Temporal Expression of Immediate Early Genes and Reduces Dendritic Spine Density during Postnatal Brain Development

Modulator Effects of Interleukin-1β and Tumor Necrosis Factor-α on AMPA-Induced Excitotoxicity in Mouse Organotypic Hippocampal Slice Cultures

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