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ABSTRACT: Kindling of the olfactory bulb using a novel fast protocol (within 24 h) was studied in rats. In target brain regions, the effects of kindling were measured on the concentration of glial fibrillary acidic protein (GFAP) by dot-blot and on the concentrations of neural cell adhesion molecule (NCAM) and the 25 kDa synaptosomal associated protein of the D3 immunoprecipitate (D3(SNAP-25)) by crossed immunoelectrophoresis. Bilateral increases in the levels of GFAP, indicating activation of astrocytes, were detected in primary olfactory cortical projection areas, including the piriform cortex, and also in the basolateral amygdala and dentate gyrus, suggesting that these regions may be functionally altered during the kindling process. In the piriform cortex and dentate gyrus increased NCAM/D3(SNAP-25) ratios found ipsilaterally at seven days after kindling probably reflect an elevated rate of synaptic remodelling. At this time, however, an overall pattern of ipsilateral decreases in the synaptic marker proteins NCAM and D3(SNAP-25) indicated that this remodelling occurred on a background of synaptic degeneration. These results confirm previous studies showing that kindling is associated with synaptic remodelling and neuronal degeneration in the hippocampal formation and extends the area of plasticity to include the piriform cortex which is believed to be central to the kindling process.
Neurochemical Research 06/1996; 21(5):585-93. · 2.24 Impact Factor
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ABSTRACT: A quantitative autoradiographic study was made on the binding of the phosphatidylinositol system ligand [3H]inositol(1,4,5)-triphosphate (IP3) to forebrain sections from electroconvulsive shock (ECS)-treated rats. One group of rats was sacrificed 1 day and 1 month, respectively, after 12 ECSs administered three times weekly for 4 weeks. SHAM-stimulated rats served as controls. A single ECS did not change the [3H]IP3 binding in any of the brain regions examined. One day after the last of 12 ECSs, a decrease in [3H]IP3 binding (21%) was found within the CA1 region of the hippocampus and the piriform cortex (39%). In rats sacrificed 1 month after the last of 12 ECSs, the [3H]IP3 binding in piriform cortex had returned to control level. In the CA1 region of the hippocampus, the binding was still decreased (24%). It is possible that changes in the phosphatidylinositol system may play a part in the neurobiological events responsible for the therapeutic effect of electroconvulsive therapy.
Biological Psychiatry 11/1995; 38(7):471-4. · 8.28 Impact Factor
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ABSTRACT: The effect of repeated electroconvulsive shock (ECS) on the activities of the three enolase isoenzymes present in rat brain: neuron specific enolase (NSE), non-neuronal enolase (NNE) and the hybrid enolase was investigated in piriform cortex. The activities were estimated on isoenzymes separated by agarose gel electrophoresis. Whereas the specific activities of NNE and hybrid enolase were unchanged in piriform cortex or ECS-treated rats the specific activity of NSE was increased by 16.3 percent (P < 0.02). The brain enolase isoenzymes are dimers of alpha- and gamma-enolase subunits. The calculated ratio between the gamma-subunit present in both NSE and hybrid enolase and the alpha-subunits present in both NNE and hybrid enolase was increased by 11.7 percent in piriform cortex of ECS-treated rats (P < 0.05). Previously, it has been shown that the gamma-subunit is only expressed in neurons whereas the alpha-subunit is expressed in both neurons and glial cells. The selectively increased expression of the enolase gamma-subunit in ECS-treated rats might either reflect an increased transcription of a whole group of neuronal genes or rather the trophic role of NSE in ECS-enhanced synaptic remodelling of the rat brain.
Neurochemical Research 12/1994; 19(12):1527-30. · 2.24 Impact Factor
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ABSTRACT: Repeated electroconvulsive stimulations represent one treatment modality for depressive disorders, but the mechanism leading to its effect is largely unknown. Studies of humans and rats have indicated that neuropeptide Y (NPY) is involved in major depression and anxiety. The purpose of the present investigation was to detect changes in the expression of preproNPY mRNA in the limbic cortex of rats exposed to electroconvulsive shocks (ECS) daily for 14 days. Twenty-four hours after the last ECS, the animals were sacrificed, brain sections were hybridized with a synthetic oligonucleotide probe complimentary to rat preproNPY mRNA. Semi-quantitative in situ hybridization histochemistry revealed an about ten-fold increase of preproNPY mRNA levels over the dentate gyrus and the piriform cortex in animals exposed to ECS compared to sham-treated controls. In the dentate gyrus dipped sections showed that the increase of gene expression took place in individual neurons in the polymorph layer. In the piriform cortex a moderate increase in the number of grains was observed over many individual cells in the pyramidal layer. These data show that the expression of preproNPY mRNA is markedly increased in specific brains regions after ECS, but whether this increase is a result of the ECS-induced seizures per se, or rather should be regarded as a protective adaptation to changes in neuronal activity pattern remains to be established.
Molecular Brain Research 07/1994; 23(4):317-22. · 2.00 Impact Factor
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ABSTRACT: Changes in hippocampal calbindin immunoreactivity were investigated after repeated electroconvulsive shocks. Adult rats were subjected to 10, 20, or 36 electroconvulsive shocks (50 mA, 0.5 seconds), given as on shock per day, 5 days a week. The rats were sacrificed and processed for calbindin immunohistochemistry 1, 2, and 30 days after the last electroconvulsive shock. In the rats receiving 10 or 20 electroconvulsive shocks, a selective reduction of the calbindin immunoreactivity of the dentate granule cell bodies, dendrites, and mossy fibers was noted 1 and 2 days after the last electroconvulsive shock. After 36 electroconvulsive shocks there was an almost complete loss of calbindin immunoreactivity from the granule cell bodies and dendrites, and the calbindin immunoreactivity of the mossy fibers was markedly reduced. Thirty days after the last of 36 electroconvulsive shocks, the calbindin immunoreactivity was back to normal. Besides demonstrating pronounced changes associated with repeated electroconvulsive shocks, the results confirm the transient nature of these changes.
Hippocampus 03/1994; 4(1):79-83. · 5.18 Impact Factor
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ABSTRACT: Increased levels of somatostatin (SS) and neuropeptide Y (NPY) have been demonstrated in the hippocampal formation after kindling. The increase might be specifically associated with kindling, or be an effect of repeated seizures per se. In order to separate these two components we studied the effects of repeated electroconvulsive shocks (ECS) on hippocampal SS-like and NPY-like immunoreactivity and SS mRNA and NPY mRNA in situ hybridization. ECS elicit seizures without having a demonstrable kindling effect. Rats were subjected to 10, 20, or 36 ECS (50 mA, 0.5 s), given as one shock per day, 5 days per week. One, 2 and 30 days after the last ECS, the rats were killed, together with sham-treated control rats, and processed for immunocytochemistry and non-radioactive in situ hybridization. There was a bilateral increase in SS-like and NPY-like immunoreactivity 1 and 2 days after the last ECS in the outer part of the dentate molecular layer. This is the terminal field of the hilar SS-containing and NPY-containing neurons, which displayed both increased immunoreactivity and hybridization signal of the cell bodies. There was also a bilateral de novo expression of NPY-like immunoreactivity in the mossy fiber system, but this was not accompanied by the appearance of a detectable NPY hybridization signal over the parent dentate granule cell bodies. The increase in SS-like immunoreactivity and hybridization signal was most pronounced in the rats that had received the largest number of ECS. This was not observed for the NPY-like immunoreactivity and hybridization signal, where the increase appeared similar after 10, 20 and 36 ECS.(ABSTRACT TRUNCATED AT 250 WORDS)
Experimental Brain Research 02/1994; 98(2):305-13. · 2.39 Impact Factor
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ABSTRACT: 1. For many years it has been discussed whether repeated electroconvulsive shock (ECS) may induce a lasting epileptogenic effect on the brain (i.e. a kindling effect). In the present study the authors investigated whether weekly ECS do exert such an effect. 2. Bipolar electrodes were implanted in amygdala of 32 rats. Following a two to three week recovery period the rats were randomly allocated to two groups. One group received 12 weekly ECS, the other 12 weekly sham-ECS. 3. Three months after the last ECS/sham-ECS, kindling was initiated. Daily stimulation, eliciting an EEG-afterdischarge was given to all the rats. The animals received a total of 15 stimulations. 4. ECS-pretreated animals did not kindle faster than the sham-group. The two groups reached stage 4 (clonic rearing) after 5.8 (ECS-group) and 5.7 (sham-group) stimulations, respectively. 5. The authors did not find a facilitated development of kindling following ECS, instead they observed a slight, yet statistically significant inhibition of the development of the maximally generalized kindling-seizure--the stage 5 seizure--in the ECS-group. 6. In conclusion: The present study did not show a kindling effect of weekly ECS suggesting that kindling requires more than repeated elicitation of after-discharge.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/1993; 17(6):985-9. · 3.25 Impact Factor
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ABSTRACT: Seizure susceptibility to lidocaine was investigated in rats which had received repeated ECS (electroconvulsive shock). In the first experiment three groups of rats received an ECS daily for 18 days, an ECS weekly for 18 weeks, and 18 sham treatments, respectively. Twelve weeks after the last ECS all rats received a lidocaine challenge (LC) in the form of an intraperitoneal (IP) injection of lidocaine (65 mg/kg). After the injection the animals were observed for occurrence of motor seizures. A total of 67% (10/15), 47% (7/15), and 0% (0/18) of the daily, weekly, and sham groups, respectively, had motor seizures in response to the LC. In the second experiment five groups of rats received an ECS daily for 0, 1, 6, 18, and 36 days, respectively. Eighteen weeks after the last ECS all rats received an LC and 0% (0/15), 13% (2/15), 20% (3/15), 53% (8/15), and 58% (7/12), respectively, developed seizures in response to the LC. In the third experiment two groups of rats received daily ECS and sham-ECS, respectively. Twenty-four hours after the last ECS all rats received an LC. A total of 60% (9/15) of the ECS group and 0% (0/10) of the sham-ECS group had seizures in response to the LC.(ABSTRACT TRUNCATED AT 250 WORDS)
Psychopharmacologia 02/1993; 111(4):495-8. · 4.08 Impact Factor
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ABSTRACT: As neuropeptides may play a role in the electrical kindling model of epileptogenesis, hippocampal somatostatin, Met-enkephalin and cholecystokinin were studied by immunocytochemistry in rats 24 h following full hippocampal kindling (three stage 5 seizures). As control animals we used sham-kindled rats, unoperated rats and rats subjected to a single electroshock-induced seizure. In addition, the distribution of septohippocampal, cholinergic fibers and hippocampal mossy fibers were studied by histochemistry. The important finding was that after kindling there was, as compared to unoperated control, (1) a marked increase of somatostatin immunoreactivity in cell bodies in the dentate hilus and their presumed projections area in the outer parts of the dentate molecular layer, and (2) a marked increase of Met-enkephalin immunoreactivity in hippocampal mossy fiber terminals. We found no evidence of aberrant sprouting of mossy fiber collaterals in the fascia dentata.
Neuroscience Letters 11/1990; 118(1):33-6. · 2.11 Impact Factor
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ABSTRACT: Hippocampal kindling was investigated in rats with a 6-hydroxydopamine-induced lesion of the forebrain catecholamine system after implantation of neural tissue from the fetal locus coeruleus region either bilaterally into the amygdala-piriform cortex (i.e., distant to the kindling site) or unilaterally into the hippocampus (close to the kindling site). Lesioned animals with either sham grafts or control grafts consisting of fetal striatal tissue showed a kindling rate much faster than that of normal controls. In contrast, in rats with bilateral locus coeruleus grafts in the amygdala-piriform cortex (implanted at three sites) the development of seizures was similar to that of controls and significantly slower than that in lesioned animals with sham grafts. All these animals had bilateral surviving grafts with a mean of 125 noradrenergic cells per implantation site. In the animals with locus coeruleus grafts in the stimulated hippocampus the kindling rate did not differ from that in the lesioned animals with control grafts. Most of these animals had large surviving grafts and showed a dense noradrenergic reinnervation of the implanted hippocampus. The present findings indicate that grafting of fetal pontine tissue (rich in noradrenergic neurons) to a site distant to the stimulation focus, but important for the generalization and spread of seizures, can retard the development of seizures in hippocampal kindling. Together with the data of our previous report this study also indicates that noradrenergic reinnervation of both hippocampi is important for the seizure-suppressant action in hippocampal kindling of locus coeruleus grafts implanted in the hippocampus.
Experimental Neurology 12/1989; 106(2):125-32. · 4.70 Impact Factor
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ABSTRACT: The effects of repeated electroconvulsive shock (ECS) and/or lidocaine treatment in the rat were studied by means of biochemical markers: GFAP (glial fibrillary acidic protein), NCAM (neural cell adhesion molecule), NSE (neuron specific enolase) and D3-protein. In adult rats given daily either ECS alone or in combination with lidocaine (experiment 1) we found that ECS significantly increased the concentration of the glial marker GFAP in limbic areas: hippocampus, amygdala, and piriform cortex. The maximal increase in GFAP was found in the piriform cortex (77%). In both piriform cortex and amygdala ECS also induced a significant decrease in D3-protein (a marker of mature synapses), but no change in NCAM (especially enriched in newly formed synapses). In piriform cortex the ratio between NCAM and D3-protein was significantly increased (4%) by ECS. The lidocaine treatment, which induced seizures in some of the animals, was without significant effect on the biochemical markers. However, multiple lidocaine-induced seizures (experiment 2) were found to be associated with a significant increase in GFAP in amygdala and piriform cortex. The study shows that seizures, whether electrically or pharmacologically induced, activate astrocytes in certain brain regions. This activation is especially pronounced in the piriform cortex and may be caused by a particularly marked synaptic vulnerability and remodeling in this area, as demonstrated by the increased NCAM/D3-ratio. Synaptic remodeling and activation of astrocytes may well influence brain function and could play a role in the chain of neurobiological events underlying the clinical effects of electroconvulsive therapy (ECT).
Biological Psychiatry 33(11-12):794-800. · 8.28 Impact Factor
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ABSTRACT: Electroconvulsive shock (ECS) has anticonvulsant properties while a proconvulsant effect has not, so far, been documented. In the present experiments, we determine whether repeated ECSs lead to an increased seizure susceptibility to lidocaine (lignocaine) in rats. Furthermore, we investigated whether ECS will cause prolonged changes in the locomotion and exploratory activity of the animals. Two groups of rats received 18 ECSs: the first group (ECS-WEEKLY) was given ECS once a week, the second (ECS-DAILY) once a day. A third group (ECS-SHAM) received only sham ECS. Five, as well as 10 weeks after the last ECS, the ECS-WEEKLY group made significantly fewer "hole visits" in an eight hole box than did the ECS-SHAM group. The ECS-DAILY group also made fewer hole visits than the ECS-SHAM group, but the difference was only significant ten weeks after the last ECS. No significant difference in locomotor activity was found. Twelve weeks after the last ECS, all rats received an injection of a high dose of lidocaine (65 mg/kg i.p.). ECS was observed to have a significant effect on the number of animals convulsing in response to the lidocaine challenge. Sixty percent (6/10) of the animals in the ECS-WEEKLY group and 20% (2/10) of those in the ECS-DAILY group convulsed, whereas none of the animals (0/12) in the ECS-SHAM group had convulsions. Thus, the present study shows that ECS may induce prolonged changes in the exploratory behaviour of rats and in their sensitivity to the convulsant effects of lidocaine.
Journal of Psychiatric Research 27(1):89-94. · 4.66 Impact Factor
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ABSTRACT: Fully hippocampus-kindled rats were examined 1 day and 1 month after the last stimulation for changes in somatostatin (SS)-, neuropeptide Y (NPY)-, and calbindin (CaBP)-immunoreactivity (ir) and SS- and NPY-mRNA in situ hybridization (ISH). One day after the last stimulation, there was marked, bilateral increase in SS- and NPY-ir in the outer part of the dentate molecular layer. The cell bodies of dentate hilar SS- and NPY-containing neurons, known to project to this area, also appeared to display increased immunoreactivity as well as an increased ISH signal for SS and NPY mRNA. Bilateral de novo expression of NPY-ir in dentate mossy fiber projection to dentate hilus and CA3 was also evident, but we noted no corresponding NPY-mRNA signal in the parent cell bodies, the dentate granule cells. After 1 month, the levels of NPY-ir and ISH signal appeared essentially normal. In contrast, the levels of SS apparently were decreased, although not yet normal. CaBP-ir was markedly and selectively reduced in dentate granule cell bodies, dendrites, and mossy fibers 1 day after the last stimulation, but after 1 month CaBP-ir appeared essentially normal. Because kindling, once established, is a permanent phenomenon, the observed transient changes in SS, NPY, and CaBP in specific hippocampal terminal fields and neuronal populations cannot be associated specifically with kindling. Rather, they relate to the repeated high-frequency stimulations and may serve as protective measures against deleterious effects of such stimulations.
Epilepsia 35(6):1299-308. · 3.96 Impact Factor
