Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholecystokinin (CCK) can be a potent anticonvulsant neuropeptide in certain seizure models. Therefore, we examined whether seizures produced by electrical kindling of the amygdala or electroconvulsive seizures (ECS) would affect the expression of CCK mRNA in rat brain. Following a single kindled seizure, CCK mRNA expression was decreased about 20-58% in the amygdala. In contrast, after multiple consecutive kindled seizures, CCK mRNA expression was increased in the amygdala, cerebral cortex, CA1 pyramidal cell layer of the hippocampus and dentate hilus. A single ECS produced no effect on CCK mRNA expression, but multiple ECS increased expression in the interneurons of the hippocampus 24 h after the last seizure. Since seizures produced by ECS can be anticonvulsant to further ECS or kindled seizures, the CCK increases in the hippocampus may represent a compensatory anticonvulsant adaptation observed in both models. Overall, the kindling-induced alterations in CCK expression appear to be more complex involving multiple brain regions and distinct temporal properties.
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PMID:Changes in cholecystokinin mRNA expression after amygdala kindled seizures: an in situ hybridization study. 871 64

Cholecystokinin-octapeptide (CCK-8S) is widely distributed in neurones of the central nervous system, where it is thought to act as a transmitter or modulator. CCK-8S has been shown to exert anti-convulsant activity in animal seizure models and changes in cortical and hippocampal CCK-immunoreactivity and preproCCK messenger RNA (mRNA) have been reported following electrically- and chemically-induced seizures. In the present study, the spatiotemporal effect of amygdaloid-kindled seizures on levels of preproCCK messenger RNA in rat brain were determined using quantitative in situ hybridization histochemistry. Stimulation-evoked seizures produced bilateral increases (45-70%) in preproCCK mRNA throughout layers II-III of the cerebral cortex. These increases were rapidly induced, occurring 30-60 min after the last stage 5 seizure, but transient, as no significant changes were detected after 2 h, or subsequently at 24 or 72 h, or 2-8 weeks, post-stimulation. Rapid changes in the relative levels of preproCCK mRNA, post-seizure, suggest a possible stabilization of preproCCK transcripts and increased production of CCK-8S peptide, which may be involved in anticonvulsant mechanisms in response to the acute seizures.
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PMID:Rapid but transient increases in cholecystokinin mRNA levels in cerebral cortex following amygdaloid-kindled seizures in the rat. 873 11

Recent studies have demonstrated that neuropeptide expression in forebrain neurons is responsive to changes in physiological activity. This is particularly true in the hippocampus where the expression of various neuropeptides has been reported to change in distinct neuronal populations in response to seizure activity. The aim of this work is to review and integrated the information on the pathological changes and functional modifications in neuropeptide systems of the hippocampal formation in kindling and other models of limbic epilepsy. This will be done by presenting a study in which we investigated the changes in the expression of somatostatin, neuropeptide Y (NPY), neurokinin B (NKB) and cholecystokinin-octapeptide (CCK) in the rat hippocampal principal neurons during and after kindling of the hippocampus using immunocytochemistry and in situ hybridization analysis of mRNA. NPY-IR was transiently expressed in the granule cells/mossy fibres after the preconvulsive stage 2 and 2 days but not 1 week after three consecutive tonic-clonic seizures (stage 5). A more pronounced increase was observed in NKB-IR lasting 1 week after kindling acquisition. Only the NKB mRNA expression was enhanced in granule cells at these intervals. At stages 2 and 5, somatostatin- and NPY-IR and their mRNA levels were markedly increased in interneurons in the deep hilus and in the polymorphic cell layer and their presumed projections to the outer molecular layer of the dentate gyrus. NKB- and CCK-IR and their mRNAs were highly expressed in basket cells at both stages of kindling. Their IR was increased in the inner molecular layer of the dentate gyrus in the ventral hippocampus. Peptide-containing neurons in the hilus appeared well preserved in spite of a reduction of Nissl stained cells by 24 % in the stimulated and contralateral hippocampus at stage 5. In the hippocampus proper, somatostatin and NPY-IR were enhanced in the stratum lacunosum molecular while CCK-IR fibres and its mRNA were particularly expressed in the pyramidal cell layer. The number of Somatostatin-, NKB- and CCK-IR cells was increased in the subiculum. The intensity of these changes was similar 2 days after stages 2 or 5 of kindling. Less pronounced effects were observed 1 week after kindling completion. These results, in the frame of the literature data, suggest that lasting functional changes occur in distinct neuropeptide-containing neurons during limbic epileptogenesis. This may have profound effects on synaptic transmission and contribute to modulate hippocampal excitability.
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PMID:Neuropeptides-immunoreactivity and their mRNA expression in kindling: functional implications for limbic epileptogenesis. 887 84

Using the P77PMC strain of rat, which is genetically prone to audiogenic seizures, and also has decreased levels of cholecystokinin (CCK), we examined the analgesic response to peripheral electrical stimulation, which is, in part, opiate-mediated. A number of studies have suggested that CCK may function as an antagonist to endogenous opiate effects. Therefore, we hypothesized that the P77PMC animals would show an enhanced analgesic response based on their decreased CCK levels producing a diminished endogenous opiate antagonism. We found that the analgesic effect on tail flick latency produced by 100 Hz peripheral electrical stimulation was more potent and longer lasting in P77PMC rats than in control rats. Moreover, the potency of the stimulation-produced analgesia correlated with the vulnerability to audiogenic seizures in these rats. We were able to block the peripheral electrical stimulation-induced analgesia (PSIA) using a cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay showed that the content of CCK-8 in cerebral cortex, hippocampus and periaqueductal gray was much lower in P77PMC rat than in controls. These results suggest that low CCK-8 content in the central nervous system of the P77PMC rats may be related to the high analgesic response to peripheral electrical stimulation, and further support the notion that CCK may be endogenous opiate antagonist.
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PMID:Rats with decreased brain cholecystokinin levels show increased responsiveness to peripheral electrical stimulation-induced analgesia. 903 5

Kindling, a model of temporal lobe epilepsy, induces a number of neuropeptides including corticotropin-releasing factor (CRF). CRF itself can produce limbic seizures which resemble kindling in some aspects. However, tolerance to the convulsant effects of CRF develops rapidly. Hypothetically, this could be explained should seizures also induce the CRF-binding protein (CRF-BP), which has been postulated to restrict the actions of CRF. Therefore, in the present study, we used in situ hybridization to examine the effects of amygdala-kindled seizures on the mRNA levels of CRF and CRF-BP. Kindled seizures markedly elevated CRF and CRF-BP in the dentate gyrus of rats. CRF and CRF-BP were induced almost exclusively in GABAergic interneurons of the dentate hilus. The CRF and CRF-BP interneurons also expressed neuropeptide Y but not cholecystokinin. CRF appeared to have an excitatory role in the dentate gyrus as it decreased the afterhyperpolarization of dentate granule neurons. These results suggest that CRF may contribute to the development of amygdala kindling. However, the compensatory induction of CRF-BP may serve to limit the excitatory effects of CRF in the dentate gyrus.
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PMID:Amygdala-kindled seizures increase the expression of corticotropin-releasing factor (CRF) and CRF-binding protein in GABAergic interneurons of the dentate hilus. 903 16

To evaluate the potential for lipofectin-mediated central nervous system gene transfer, the plasmid coding for cholecystokinin was administered intracerebroventricularly to rats, which have congenital audiogenic seizures and high responses to peripheral electric stimulation-induced analgesia. Previous studies had shown that low brain cholecystokinin levels may be the neurochemical variable of rat's audiogenic seizure and high responses to the analgesia because cholecystokinin is an anticonvulsant and anti-opioid neuropeptide. Gene transfer of cholecystokinin corrected the increased susceptibility to audiogenic seizures and the high responses to analgesia for about one week. Similar administration of plasmid expressing beta-galactosidase indicated that the vector mainly transfected ependymal cells lining the ventricle and pia mater cells. The increased cholecystokinin messenger RNA and immunoreactivity in the hippocampus following stereotactic intrahippocampal administration of cholecystokinin plasmid was also demonstrated with in situ hybridization and immunohistochemistry techniques. These results suggest that lipofectin-mediated gene transfer will be useful for studies of brain function, the modification of behavior and gene therapy for central nervous system disorders.
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PMID:Lipofectin-facilitated transfer of cholecystokinin gene corrects behavioral abnormalities of rats with audiogenic seizures. 904 70

Cholecystokinin (CCK) is found co-localized with the inhibitory neurotransmitter GABA in interneurons of the hippocampus. Also, CCK receptors are found in abundance in this brain region. The possibility that CCK alters interneuron activity was examined using whole-cell current- and voltage-clamp recordings from visualized interneurons in the stratum radiatum of area CA1 in rat hippocampal slices. The effect of CCK on GABA-mediated IPSCs was also determined in pyramidal neurons. The sulfated octapeptide CCK-8S increased action potential frequency or generated inward currents in the majority of interneurons. These effects of CCK persisted in the presence of tetrodotoxin and cadmium, suggesting that they were direct. Current-voltage plots revealed that CCK-8S inhibited a conductance that was linear across command potentials and reversed near the equilibrium potential for K+ ions. The K+ channel blocker tetraethylammonium (10 mM) generated inward currents similar to those initiated by CCK, and it occluded the effect of the peptide. BaCl2 (1 mM) and 4-aminopyridine (2 mM) did not alter the effect of CCK. The CCKB receptor antagonist PD-135,158 completely blocked the inward currents generated by CCK-8S. CCK also resulted in an increase in spontaneous action potential-dependent IPSC frequency, but no changes in action potential-independent miniature IPSCs or evoked IPSCs in pyramidal neurons. These results provide evidence that CCK can depolarize hippocampal interneurons through the inhibition of a resting K+ conductance, leading to increased tonic inhibition of pyramidal neurons. This action of CCK may contribute to its anticonvulsant properties, as observed in limbic seizure models.
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PMID:Cholecystokinin increases GABA release by inhibiting a resting K+ conductance in hippocampal interneurons. 918 37

Cholecystokinin exerts a potent antiepileptic action in mammalian auditory system and undergoes seizure-mediated up-regulation. The present study investigated cholecystokinin messenger RNA expression in the reciprocally-connected auditory thalamus and cortex in the rat. Immunofluorescence in situ hybridization was performed using a 24-base cholecystokinin-messenger RNA oligonucleotide probe. Corticothalamic projection neurons were identified by means of the retrograde fluorescent tracer rhodamine latex microspheres injected into the medial geniculate body. In our experiments, cholecystokinin messenger RNA transcripts were found in about 80% of neurons located within the reciprocally-connected regions of the medial geniculate body and the auditory cortices. These observations provide evidence of cholecystokinin production in the reciprocally-connected regions of the auditory thalamus and cortex, the structures which jointly create the thalamo-corticothalamic circuit which has been implicated in seizure genesis.
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PMID:Expression of cholecystokinin messenger RNA in reciprocally-connected auditory thalamus and cortex in the rat. 921 54

We sought to describe quantitatively the morphological and functional changes that occur in the dentate gyrus of kainate-treated rats, an experimental model of temporal lobe epilepsy. Adult rats were treated systemically with kainic acid, and, months later, after displaying spontaneous recurrent motor seizures, their dentate gyri were examined. Histological, immunocytochemical, and quantitative stereological techniques were used to estimate numbers of neurons per dentate gyrus of various classes and to estimate the extent of granule cell axon reorganization along the septotemporal axis of the hippocampus in control rats and epileptic kainate-treated rats. Compared with control rats, epileptic kainate-treated rats had fewer Nissl-stained hilar neurons and fewer somatostatin-immunoreactive neurons. There was a correlation between the extent of hilar neuron loss and the extent of somatostatin-immunoreactive neuron loss. However, functional inhibition in the dentate gyrus, assessed with paired-pulse responses to perforant-pathway stimulation, revealed enhanced, and not the expected reduced, inhibition in epileptic kainate-treated rats. Numbers of parvalbumin- and cholecystokinin-immunoreactive neurons were similar in control rats and in most kainate-treated rats. A minority (36%) of the epileptic kainate-treated rats had fewer parvalbumin- and cholecystokinin-immunoreactive neurons than control rats, and those few (8%) with extreme loss in these interneuron classes showed markedly hyperexcitable dentate gyrus field-potential responses to orthodromic stimulation. Compared with control rats, epileptic kainate-treated rats had larger proportions of their granule cell and molecular layers infiltrated with Timm stain. There was a correlation between the extent of abnormal Timm staining and the extent of hilar neuron loss. Granule cell axon reorganization and dentate gyrus neuron loss were more severe in temporal vs. septal hippocampus. These findings from the dentate gyrus of epileptic kainate-treated rats are strikingly similar to those reported for human temporal lobe epilepsy, and they suggest that neuron loss and axon reorganization in the temporal hippocampus may be important in epileptogenesis.
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PMID:Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats. 930 Jul 66

Northern Blot and hybrization in situ techniques were used to investigate the effect of electroacupuncture (EA) on the changes of cholecystokinin (CCK) mRAN levels of the hippocampus in rat penicillin-induced epilepsy model. Epilepsy can significantly increase CCK mRNA levels in dentate gyrus and CA3 areas of hippocampus in diencephalic sections after penicillin-induced seizure, whereas EA not only can attenuate the seizure behaviors and EEG changes, but also can decrease the increase of CCK mRNA contents induced by the seizure. However, in the subiculum, dentate gyrus and CA3 areas of mesencephalic sections of rat hippocampus, EA can further increase the enhancement of CCK mRNA concentration induced by penicillin-induced seizure. The results suggest that EA inhibitory effects on the seizure's behaviors and epileptiform activities may be related to the alteration of CCK gene expression in the different area of hippocampus.
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PMID:[Effect of electroacupuncture on cholecystokinin gene expression in rat hippocampus during penicillin-induced epileptic seizure]. 938 77


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