Effect of inhibitors of protein synthesis on the development of kindled seizures in rats

Jonec, Viliam; Wasterlain, Claude G.

doi:10.1016/0014-4886(79)90199-7

Cited by 49 publications

(20 citation statements)

References 17 publications

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“…Indeed, cycloheximide did not block the KA-mediated induction of TIMP-1 mRNA but did block the induction of Fos protein, indicating that protein synthesis was successfully inhibited, as previously demonstrated in vivo (Jonec and Wasterlain, 1979;Goto et al, 1990;Papas et al, 1992). This raises the possibility that activity-dependent TIMP-1 expression is under the control of consitutively expressed transcription factors that are post-translationally activated.…”

Section: The Early Timp-1 Mrna Induction In Neurons Is Independent Ofmentioning

confidence: 52%

Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Is Differentially Induced in Neurons and Astrocytes after Seizures: Evidence for Developmental, Immediate Early Gene, and Lesion Response

et al. 1997

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We investigated in vivo the expression of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in the rat CNS after kainate (KA)-induced excitotoxic seizures. In situ hybridization revealed that TIMP-1 mRNA is induced rapidly and massively in most regions of the adult forebrain after KA treatment. Neuronal activity seems to be necessary but not sufficient to trigger TIMP-1 induction, because it is not observed in seizing 10-d-old pups, unlike what is observed in 21-and 35-d-old animals after seizures. The rapid induction of TIMP-1 is not prevented by the inhibitor of protein synthesis cycloheximide, suggesting that, after seizures, TIMP-1 is induced in neurons as an immediate early gene (IEG). The initial neuronal upregulation is followed by enhanced expression in astrocytes, as assessed by double-labeling experiments. In the hippocampus rapid increases in mRNA are followed by relatively delayed (8 hr after KA) increases in TIMP-1 immunoreactivity in the perisomatic and dendro-axonic areas, suggesting secretion of the protein. At 3 d after KA treatment, strong immunoreactivity is found in astrocytes and in the cell bodies and dendro-axonic projections of resistant neurons such as the dentate granule cells. Taken together, the results suggest that TIMP-1 may be instrumental for neurons and astrocytes in coupling early cellular events triggered by seizures with the regulation of long-lasting changes involved in tissue reorganization and/or neuroprotection.

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Section: The Early Timp-1 Mrna Induction In Neurons Is Independent Ofmentioning

confidence: 52%

Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Is Differentially Induced in Neurons and Astrocytes after Seizures: Evidence for Developmental, Immediate Early Gene, and Lesion Response

et al. 1997

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“…Thereafter, the effect quickly wears off and according to biochemical indicators, 2 h after administration protein synthesis is back to normal levels (Flood et al, 1973;Jonec & Wasterlain, 1979). Therefore, anisomycin was administered 15 min prior to stimulation so that the stimulus was applied at the height of the protein synthesis block.…”

Section: Anisomycin Experimentsmentioning

confidence: 99%

“…Anisomycin has been shown to prevent valine and lysine incorporation into brain proteins in a dose-dependent manner (Flood et al, 1973;Jonec & Wasterlain, 1979) which indicates that protein synthesis is blocked at the level of translation. Molecular biology of anisomycin action shows that the drug prevents formation of peptide bonds by immobilizing ribosomes and thus acts as a protein-chain-elongation inhibitor (Pestka, 1971;Grollman & Huang, 1972).…”

Section: Anisomycin Experimentsmentioning

confidence: 99%

Effect of anisomycin on stimulation-induced changes in dendritic spines of the dentate granule cells

et al. 1982

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Tetanic stimulation of the entorhinal area induces significant enlargement of the average dendritic spine area and perimeter in the middle and distal thirds of the dentate molecular layer 4 and 90 min following stimulation. Four minutes after stimulation, the differences between the stimulated and control animals were 20% for the dendritic spine area and 9% for the perimeter in the middle third, and in the distal third 32 and 14%, respectively. Ninety minutes after stimulation the differences were 28 and 11% for the area and perimeter in the middle third, and 33 and 18% in the distal third, respectively. Anisomycin at a dose of 25 mg/kg had no significant effect on the average spine area or perimeter in the various thirds of the dentate molecular layer in the 19 and 105 min post-application intervals. This dose of anisomycin given 15 min prior to the stimulation suppresses the stimulation-induced spine changes in the 4 min interval. In the 90 min interval when the effect of anisomycin on protein synthesis is largely terminated, spine enlargement reappears, being 21% higher than the controls in the middle and distal thirds. The differential effect of anisomycin on dendritic spines in the two post-stimulation intervals is discussed in relation to the effect of anisomycin on protein synthesis. The present experiments thus demonstrate that the stimulation-induced spine enlargement in the dentate fascia can be suppressed by a protein synthesis blocking drug.

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“…This enduring enhancement of synaptic efficacy, its extension only along synaptically linked stations of the stimulated circuit (7), and its strict dependence on protein synthesis (8,9) and axonal transport (7,10) have suggested that kindling should be associated with some morphological alteration of the synapse itself. It seemed reasonable to assume that a possible mechanism of long-lasting facilitation of synaptic transmission during kindling might be an increase in the number of synaptic contacts.…”

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confidence: 99%

Remodeling of synaptic architecture during hippocampal "kindling".

Geinisman

Morrell

deToledo-Morrell

1988

Proc. Natl. Acad. Sci. U.S.A.

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The "kindling" phenomenon is associated with long-lasting facilitation of synaptic transmission. A possible mechanism of such facilitation could involve changes in the number of synaptic contacts. However, previous attempts to demonstrate a synaptic morphological alteration that could account for the long-term effects ofkindling had failed, possibly due to the unavailability, at the time, of unbiased methods for synapse quantitation. Using the unbiased stereological disector technique, we estimated the number of synapses per neuron in the middle molecular layer of the hippocampal dentate gyrus in rats kindled by electrical stimulation of the medial perforant path with implanted electrodes. Unkindled but stimulated (coulodibit control) and unstimulated but implanted rats served as controls. Animals were coded and killed 4 weeks after reaching the kindling criterion of five generalized seizures. The most important results were obtained when axospinous synapses with continuous or discontinuous postsynaptic densities ("nonperforated" or "perforated" synapses) were differentially analyzed. Kindling resulted in a selective loss of nonperforated synaptic contacts in contrast to preservation of perforated ones. Furthermore, the ratio of perforated to nonperforated synapses was increased by 45% or 40% in kindled rats relative to unstimulated or coulombic controls, respectively. These findings suggest that synaptic efficacy may depend on a balance of the two synaptic types; selective elimination of nonperforated synapses may augment the potency ofremaining synaptic contacts, a process reminiscent of synaptic remodeling during development."Kindling" may be viewed as an experimental model of the formation of an engram in the brain (1, 2). It differs from all other models of synaptic plasticity (or neuronal models of memory) by reason of its extraordinary duration. After only a few exposures to a low-level, localized electrical stimulus, the synaptic responsiveness of the stimulated circuit undergoes an augmentation that persists, without further reinforcement, for many months.In the kindling paradigm (3, 4), a subthreshold electrical stimulus is repeatedly delivered to a local brain area once or twice a day for a duration of 1-2 sec. When first applied, the electrical stimulation results in only brief afterdischarge (AD) and no behavioral alteration. Without any change in stimulation parameters, the AD gradually increases in duration and spreads from the stimulated area to increasingly distant, though synaptically connected, brain regions. A progressive alteration of behavior is also seen, beginning with momentary arrest of ongoing locomotor activity and proceeding through localized twitching to a generalized seizure. Once generalized seizures have occurred, cessation of stimulation for weeks, months, or even years does not result in loss of the newly acquired, electrophysiologically and behaviorally defined change (2, 5, 6). Reintroduction of the original stimulus, which was behaviorally ineffective to begin with, ...

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Effect of inhibitors of protein synthesis on the development of kindled seizures in rats

Cited by 49 publications

References 17 publications

Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Is Differentially Induced in Neurons and Astrocytes after Seizures: Evidence for Developmental, Immediate Early Gene, and Lesion Response

Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Is Differentially Induced in Neurons and Astrocytes after Seizures: Evidence for Developmental, Immediate Early Gene, and Lesion Response

Effect of anisomycin on stimulation-induced changes in dendritic spines of the dentate granule cells

Remodeling of synaptic architecture during hippocampal "kindling".

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