Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure

Suzukawa, Junko; Omori, Kyoko; Okugawa, Gaku; Fujiseki, Yoshito; Heizmann, Claus W.; Inagaki, Chiyoko

doi:10.1016/s0006-8993(99)01554-1

Cited by 14 publications

(5 citation statements)

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“…Given the significant reduction of immunoreactive somata in three of the four populations of interneurons we asked whether there might be an actual loss of GABAergic cells in ErbB4−/− mice or rather a down-regulation of the marker proteins, because at least PV-expression is well known to be activity-dependent and highly variable (Scotti et al, 1997; Suzukawa et al, 1999). We therefore went on to compare the ND of GAD67-immunoreactive cells in the hippocampus of WT and ErbB4−/− mice.…”

Section: Resultsmentioning

confidence: 99%

Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout mice

2009

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Neuregulins (NRGs) are ligands of ErbB receptor tyrosine kinases. The NRG1-ErbB4 pathway has been shown to modulate hippocampal synaptic plasticity and network oscillations in the adult rodent brain. In order to identify cells that mediate these effects here we determine the expression pattern of ErbB4 in four functionally distinct classes of interneurons that represent the majority of all inhibitory neurons in the hippocampus. Based on data from 15 mice and 25,000 cells, we show that ErbB4 is expressed in cells that are positive for cholecystokinin (CCK, 54%), parvalbumin (PV, 42%), or neuronal nitric oxide synthase (nNOS, 39%) in a layer-specific and region-specific manner, whereas cells expressing somatostatin (SOM) are rarely immunoreactive for ErbB4 (1%). We next compared the numerical density (cells/mm3) and the distribution of interneurons between ErbB4−/− mice and wildtype controls. Based on data from 25 mice and 56,000 cells, we detected reductions of PV-positive and nNOS-positive cells in knockouts (−24% and −27%, respectively) but only a minor reduction of CCK-positive cells; no changes in SOM-positive cells were observed. The overall reduction of interneurons was verified by quantification of GAD67-immunoreactive cells (−24% in ErbB4−/− mice). The reduction of interneurons along the dorsoventral axis was more severe in intermediate and ventral portions than in the dorsal hippocampus, and regional reductions occurred in the CA1-3 regions and subiculum, whereas we found no significant changes in the dentate gyrus. The expression by different populations of interneurons suggests that ErbB4 can modulate several microcircuits within the hippocampus and mediate the previously reported effects of NRG1 on network oscillations and synaptic plasticity. The selective reduction of GABAergic cells in ErbB4−/− mice is consistent with the role of NRG-ErbB4 signaling in the generation and migration of interneurons during development, and with neuronal and behavioral functional deficits in adult ErbB4 knockouts.

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Section: Resultsmentioning

confidence: 99%

Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout mice

2009

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“…It is increasingly recognised that experimental seizures can influence the expression of many genes, the most widely characterised of which are the immediate early genes, such as c-fos, which are upregulated within 1 h of seizure activity in a number of models (35)(36)(37)(38)(39). Kindled seizures, and those induced by kainic acid, have been reported to increase the mRNA levels of several neuropeptides (40)(41)(42)(43)(44), whereas audiogenic seizures are associated with increased expression of cholecystokinin (45) and the ubiquitous c-fos (46,47) and a reduced expression of tyrosine hydroxylase (48).…”

Section: Discussionmentioning

confidence: 99%

Regional Expression of Multidrug Resistance Genes in Genetically Epilepsy‐prone Rat Brain after a Single Audiogenic Seizure

et al. 2002

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Summary:Purpose: The multidrug resistance (mdr) gene family encodes the drug transport macromolecule P-glycoprotein (P-gp), which contributes to the functionality of the bloodbrain barrier. Recent evidence suggests that P-gp-mediated drug extrusion may play a facilitatory role in refractory epilepsy. We investigated the regional expression of mdr genes in genetically epilepsy-prone rat (GEPR) brain after a single audiogenic seizure.Methods: Three groups of adult male GEPRs (n ‫ס‬ 5/group) were exposed to a seizure-inducing audiogenic stimulus and killed at 4 h, 24 h, and 7 days thereafter. A further group (n ‫ס‬ 5) served as a stimulus-naïve control. Expression of mdr1a and mdr1b in distinct anatomic brain regions (cortex, midbrain, pons/medulla, hippocampus) was determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in the presence of competitive internal standards.Results: When compared with control, mdr1a expression in cortex and midbrain was significantly (p < 0.05) increased at 24 h after a single audiogenic seizure. Cortical mdr1a expression remained elevated at 7 days after stimulus. In contrast, mdr1a expression in pons/medulla and hippocampus was unchanged.The mdr1b isoform was quantifiable in hippocampus alone and not influenced by seizure activity.Conclusions: These findings suggest that acute seizures in the GEPR can induce the expression of mdr genes. The pattern of increased expression appears to follow the anatomic pathway of audiogenic seizures in these animals, with initiation in the midbrain and propagation to the cortex. Further studies are required to investigate the effects of recurrent seizure activity and to characterise mdr expression in other experimental seizure models.

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“…5). Previous studies have reported that seizures result in a loss of certain hippocampal interneurons, including those expressing the calcium-binding protein parvalbumin (Buckmaster and Dudek, 1997;Suzukawa et al, 1999); these interneurons provide inhibitory input to pyramidal cells. As demonstrated in Figure 5, the density of parvalbumin-like immunoreactive neurons was decreased substantially in both the hippocampus and overlying retrosplenial cortex of KCC2 homozygous mice, with no difference between wild-type and heterozygous mice.…”

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confidence: 99%

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

et al. 2002

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Four genes encode electroneutral, Na+-independent, K-Cl cotransporters. KCC2, is exclusively expressed in neurons where it is thought to drive intracellular Cl- to low concentrations and shift the reversal potential for Cl- conductances such as GABA(A) or glycine receptor channels, thus participating in the postnatal development of inhibitory mechanisms in the brain. Indeed, expression of the cotransporter is low at birth and increases postnatally, at a time when the intracellular Cl- concentration in neurons decreases and gamma-aminobutyric acid switches its effect from excitatory to inhibitory. To assert the significance of KCC2 in neuronal function, we disrupted the mouse gene encoding this neuronal-specific K-Cl cotransporter. We demonstrate that animals deficient in KCC2 exhibit frequent generalized seizures and die shortly after birth. We also show upregulation of Fos, the product of the immediate early gene c-fos, and the significant loss of parvalbumin-positive interneurons, both indicative of brain injury. The regions most affected are the hippocampus and temporal and entorhinal cortices. Extracellular field potential measurements in the CA1 hippocampus exhibited hyperexcitability. Application of picrotoxin, a blocker of the GABA(A) receptor, further increased hyperexcitability in homozygous hippocampal sections. Pharmacological treatment of pups showed that diazepam relieved the seizures while phenytoin prevented them between postnatal ages P4-P12. Finally, we demonstrate that adult heterozygote animals show increased susceptibility for epileptic seizure and increased resistance to the anticonvulsant effect of propofol. Taken together, these results indicate that KCC2 plays an important role in controlling CNS excitability during both postnatal development and adult life.

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Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure

Cited by 14 publications

References 50 publications

Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout mice

Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout mice

Regional Expression of Multidrug Resistance Genes in Genetically Epilepsy‐prone Rat Brain after a Single Audiogenic Seizure

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

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