Selective loss of GABA neurons in area CA1 of the rat hippocampus after intraventricular kainate

Morin, Frédéric; Beaulieu, Clermont; Lacaille, Jean‐Claude

doi:10.1016/s0920-1211(98)00033-3

Cited by 77 publications

(54 citation statements)

References 23 publications

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“…In theory, the loss of neurons, especially GABAergic interneurons, would account nicely for the neuronal hyperexcitability in epilepsy (Sloviter, 1987;Morin et al, 1998;Cossart et al, 2001). In this study, although NR2A and NR2B antagonists offered similar degrees of neuroprotection, only NR2A antagonist prevented epileptogenesis.…”

Section: Discussionmentioning

confidence: 50%

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Qian

He²,

Hu³

et al. 2007

J. Neurosci.

144

103

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Fleeting activation of NMDA receptors (NMDARs) induces long-term modification of synaptic connections and refinement of neuronal circuits, which may underlie learning and memory and contribute to pathogenesis of a diversity of neurological diseases, including epilepsy. Here, we found that NR2A and NR2B subunit-containing NMDARs were coupled to distinct intracellular signaling, resulting in differential BDNF expression and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Selective activation of NR2A-containing NMDARs increased BDNF gene expression. Activation of NR2B-containing NMDARs led to ERK1/2 phosphorylation. Furthermore, selectively blocking NR2A-containing NMDARs impaired epileptogenesis and the development of mossy fiber sprouting in the kindling and pilocarpine rat models of limbic epilepsy, whereas inhibiting NR2B-containing NMDARs had no effects in epileptogenesis and mossy fiber sprouting. Interestingly, blocking either NR2A- or NR2B-containing NMDARs decreased status epilepticus-induced neuronal cell death. The specific requirement of NR2A and its downstream signaling for epileptogenesis implicates attractive new targets for the development of drugs that prevent epilepsy in patients with brain injury.

show abstract

Section: Discussionmentioning

confidence: 50%

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Qian

He²,

Hu³

et al. 2007

J. Neurosci.

144

103

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“…Once CA1 neurons activate, these OA-SLM interneurons will normally shut off the temporoammonic input in a feedback manner, preventing reentrant activation and further regulating this pathway (Lacaille et al, 1987;Yanovsky et al, 1997;Ang et al, 2005). However, in epileptic animals, these interneurons are selectively lost (Houser and Esclapez, 1996;Morin et al, 1998;Dinocourt et al, 2005), which would remove a further check on this pathway, allowing reentrant activity to proceed unchecked. This could potentially provide an additional mechanism whereby the direct entorhinal cortical/ CA1 pathway may facilitate seizure discharge initiation in limbic circuits.…”

Section: Discussionmentioning

confidence: 99%

Massive and Specific Dysregulation of Direct Cortical Input to the Hippocampus in Temporal Lobe Epilepsy

Ang

Carlson²,

Coulter³

2006

J. Neurosci.

135

115

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Epilepsy affects 1-2% of the population, with temporal lobe epilepsy (TLE) the most common variant in adults. Clinical and experimental studies have demonstrated hippocampal involvement in the seizures underlying TLE. However, identification of specific functional deficits in hippocampal circuits associated with possible roles in seizure generation remains controversial. Significant attention has focused on anatomic and cellular alterations in the dentate gyrus. The dentate gyrus is a primary gateway regulating cortical input to the hippocampus and, thus, a possible contributor to the aberrant cortical-hippocampal interactions underlying the seizures of TLE. Alternate cortical pathways innervating the hippocampus might also contribute to seizure initiation. Despite this potential importance in TLE, these pathways have received little study. Using simultaneous voltage-sensitive dye imaging and patch-clamp recordings in slices from animals with epilepsy, we assessed the relative degree of synaptic excitation activated by multiple cortical inputs to the hippocampus. Surprisingly, dentate gyrus-mediated regulation of the relay of cortical input to the hippocampus is unchanged in epileptic animals, and input via the Schaffer collaterals is actually decreased despite reduction in Schaffer-evoked inhibition. In contrast, a normally weak direct cortical input to area CA1 of hippocampus, the temporoammonic pathway, exhibits a TLE-associated transformation from a spatially restricted, highly regulated pathway to an excitatory projection with Ͼ10-fold increased effectiveness. This dysregulated temporoammonic pathway is critically positioned to mediate generation and/or propagation of seizure activity in the hippocampus.

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“…Postmortem studies have suggested that GABA cells in the ACCx of bipolar subjects may fall victim to oxidative stress (Benes et al, 1992;Benes et al, 2000) that occurs in response to excessive amygdalar stimulation (Benes and Beretta, 2001). On the other hand, some studies have paradoxically suggested that GABAergic cells in hippocampus may be resistant to kainic acid -induced excitotoxicity (Davenport et al, 1990), although conflicting results have been reported with less localized applications of kainic acid (Morin et al, 1998). Excessive excitatory activity in nonGABAergic cells could result in consequent changes in oxidative enzymes associated with mitochondria (Benes, 2000;Coyle and Puttfarcken, 1993).…”

Section: Discussionmentioning

confidence: 99%

DNA fragmentation is increased in non-GABAergic neurons in bipolar disorder but not in schizophrenia

Buttner

Bhattacharyya

Walsh

et al. 2007

Schizophrenia Research

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Apoptosis is thought to contribute to neuronal loss in bipolar disorder and schizophrenia, although empiric evidence in support of this idea has been lacking. In this study, we investigated whether or not apoptosis is associated with GABAergic interneurons in the anterior cingulate cortex in schizophrenia (n = 14) and bipolar disorder (n = 14) when compared to normal controls (n = 14). A double-labeling technique using the Klenow method of in situ end-labeling (ISEL) of single-stranded DNA breaks was combined with an in situ hybridization localization of mRNA for the 67 kiloDalton (kDa) isoform of glutamate decarboxylase (GAD67) and applied to the anterior cingulate cortex of 14 normal controls, 14 schizophrenics, and 14 patients with bipolar disorder matched for age and postmortem interval. An increase in Klenow-positive, GAD67-negative nuclei was observed in layer V/VI of patients with bipolar disorder, but not schizophrenics. Klenow-positive cells that were also positive for GAD67 mRNA did not show differences in either patient group. Conclusions: This is the first demonstration that there is more DNA fragmentation in cells showing no detectable GAD67 mRNA in patients with bipolar disorder than in schizophrenics or controls. These findings suggest that non-GABAergic cells may be selectively vulnerable to oxidative stress in patients with bipolar disorder.

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Selective loss of GABA neurons in area CA1 of the rat hippocampus after intraventricular kainate

Cited by 77 publications

References 23 publications

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Massive and Specific Dysregulation of Direct Cortical Input to the Hippocampus in Temporal Lobe Epilepsy

DNA fragmentation is increased in non-GABAergic neurons in bipolar disorder but not in schizophrenia

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