Early loss of interneurons and delayed subunit-specific changes in GABAA-receptor expression in a mouse model of mesial temporal lobe epilepsy

Bouilleret, Viviane; Loup, Fabienne; Kiener, Tania; Marescaux, Christian; Fritschy, Jean‐Marc

doi:10.1002/1098-1063(2000)10:3<305::aid-hipo11>3.0.co;2-i

Cited by 179 publications

(78 citation statements)

References 97 publications

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“…Consistent with this hypothesis, impressive changes in the number and connectivity of various types of GABAergic inhibitory interneurons, as well as in the expression of GABA A and GABA B receptors, has been observed both in mTLE patients and in experimental animals (8)(9)(10). However, recent experimental studies revealed that reduction of inhibition in epilepsy is not uniform but shows a characteristic spatial distribution over the surface of principal cells.…”

mentioning

confidence: 64%

“…Previous studies showed that the anatomical alterations are not limited to the principal cell population but also affect GABAergic interneurons (8). In the present investigation, we have focused on the neurochemical marker somatostatin, a neuropeptide expressed by O-LM cells, a type of dendrite-inhibiting interneuron involved in the generation of theta activity (19).…”

Section: Resultsmentioning

confidence: 95%

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Impaired hippocampal rhythmogenesis in a mouse model of mesial temporal lobe epilepsy

Dugladze

Vida

Tort

et al. 2007

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

118

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Mesial temporal lobe epilepsy (mTLE) is one of the most common forms of epilepsy, characterized by hippocampal sclerosis and memory deficits. Injection of kainic acid (KA) into the dorsal hippocampus of mice reproduces major electrophysiological and histopathological characteristics of mTLE. In extracellular recordings from the morphologically intact ventral hippocampus of KA-injected epileptic mice, we found that theta-frequency oscillations were abolished, whereas gamma oscillations persisted both in vivo and in vitro. Whole-cell recordings further showed that oriens-lacunosum-moleculare (O-LM) interneurons, key players in the generation of theta rhythm, displayed marked changes in their intrinsic and synaptic properties. Hyperpolarization-activated mixed cation currents (Ih) were significantly reduced, resulting in an increase in the input resistance and a hyperpolarizing shift in the resting membrane potential. Additionally, the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) was increased, indicating a stronger excitatory input to these neurons. As a consequence, O-LM interneurons increased their firing rate from theta to gamma frequencies during induced network activity in acute slices from KA-injected mice. Thus, our physiological data together with network simulations suggest that changes in excitatory input and synaptic integration in O-LM interneurons lead to impaired rhythmogenesis in the hippocampus that in turn may underlie memory deficit.in vitro ͉ interneurons ͉ oscillations ͉ patch-clamp ͉ in vivo

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mentioning

confidence: 64%

Section: Resultsmentioning

confidence: 95%

Impaired hippocampal rhythmogenesis in a mouse model of mesial temporal lobe epilepsy

Dugladze

Vida

Tort

et al. 2007

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

118

View full text Add to dashboard Cite

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“…In this model after a latent period of 2 weeks, spontaneous seizures begin to occur accompanied by reactive gliosis and progressive cell loss in the CA1 and CA3 regions of the injected hippocampus over 4 -6 weeks (Suzuki et al, 1995;Bouilleret et al, 2000). Adult Adk ϩ/ϩ mice were injected with a single unilateral intrahippocampal dose of 50 nl of 20 mM kainic acid (KA; n ϭ 15) or saline (control; n ϭ 6) and killed at different time points thereafter (2 hr, n ϭ 4; 1 d, n ϭ 4; 1 week, n ϭ 4; and 4 weeks n ϭ 3 after KA injection).…”

Section: Overexpression Of Adenosine Kinase In Epileptic Hippocampusmentioning

confidence: 99%

“…To investigate whether potential changes of endogenous ADK expression may contribute to epileptogenesis, a mouse model based on a unilateral injection of a low dose of kainate into the dorsal hippocampus of adult mice (Bouilleret et al, 1999(Bouilleret et al, , 2000 was used in this study. In this model, the histopathological changes occurring in human mesial temporal lobe epilepsy are closely replicated and accompanied by chronic recurrent seizures that are resistant to classic antiepileptic drugs (Riban et al, 2002), but are suppressed by activation of A 1 receptors (Gouder et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Adenosine Kinase in Epileptic Hippocampus Contributes to Epileptogenesis

Gouder¹,

Scheurer²,

Fritschy³

et al. 2004

J. Neurosci.

199

245

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Endogenous adenosine in the brain is thought to prevent the development and spread of seizures via a tonic anticonvulsant effect. Brain levels of adenosine are primarily regulated by the activity of adenosine kinase. To establish a link between adenosine kinase expression and seizure activity, we analyzed the expression of adenosine kinase in the brain of control mice and in a kainic acid-induced mouse model of mesial temporal lobe epilepsy. Immunohistochemical analysis of brain sections of control mice revealed intense staining for adenosine kinase, mainly in astrocytes, which were more or less evenly distributed throughout the brain, as well as in some neurons, particularly in olfactory bulb, striatum, and brainstem. In contrast, hippocampi lesioned by a unilateral kainic acid injection displayed profound astrogliosis and therefore a significant increase in adenosine kinase immunoreactivity accompanied by a corresponding increase of enzyme activity, which paralleled chronic recurrent seizure activity in this brain region. Accordingly, seizures and interictal spikes were suppressed by the injection of a low dose of the adenosine kinase inhibitor 5-iodotubercidin. We conclude that overexpression of adenosine kinase in discrete parts of the epileptic hippocampus may contribute to the development and progression of seizure activity.

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“…Generally, the studies on the role of GABA A receptors in MTLE have utilized immunohistochemistry and focused on the hippocampus. Bouilleret et al (2000) investigated alterations in subunit architecture and localization of GABA A receptor subtypes immunohistochemically (a1, a2, a3, b2, b3, and g2) in the hippocampus resected from MTLE patients compared with control tissue obtained at autopsy. They found changes in GABA A receptors with reorganization of specific receptor subtypes in some cells and interneurons.…”

Section: Discussionmentioning

confidence: 99%

Amygdala gene expression of NMDA and GABA_A receptors in patients with mesial temporal lobe epilepsy

Moura¹,

Tirapelli²,

Neder³

et al. 2010

Hippocampus

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ABSTRACT:Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and affects 40% of the patients. Seizures arising from the mesial temporal lobe structures (i.e., amygdala and hippocampus) are common, whereas neocortical seizures are rare. In recent years, many studies aimed to identify the pattern of gene expression of neurotransmitters involved in molecular mechanisms of epilepsy. We used real-time PCR to quantify the expression of GABA A (subunits a1, b1, b2) and NMDA (subunits NR1, NR2A, and NR2B) receptor genes in amygdalae of 27 patients with TLE and 14 amygdalae from autopsy controls. The NR1 subunit was increased in patients with epilepsy when compared with controls. No differences were found in expression of NMDA subunits NR2A and NR2B or in a1, b1, and b2 subunits of GABA A receptors. Our results suggest that the NR1 subunit of NMDA receptors is involved in the amygdala hyperexcitability in some of the patients with TLE. V V C 2010 Wiley Periodicals, Inc.

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Early loss of interneurons and delayed subunit-specific changes in GABAA-receptor expression in a mouse model of mesial temporal lobe epilepsy

Cited by 179 publications

References 97 publications

Impaired hippocampal rhythmogenesis in a mouse model of mesial temporal lobe epilepsy

Impaired hippocampal rhythmogenesis in a mouse model of mesial temporal lobe epilepsy

Overexpression of Adenosine Kinase in Epileptic Hippocampus Contributes to Epileptogenesis

Amygdala gene expression of NMDA and GABA_A receptors in patients with mesial temporal lobe epilepsy

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Early loss of interneurons and delayed subunit-specific changes in GABAA-receptor expression in a mouse model of mesial temporal lobe epilepsy

Cited by 179 publications

References 97 publications

Impaired hippocampal rhythmogenesis in a mouse model of mesial temporal lobe epilepsy

Impaired hippocampal rhythmogenesis in a mouse model of mesial temporal lobe epilepsy

Overexpression of Adenosine Kinase in Epileptic Hippocampus Contributes to Epileptogenesis

Amygdala gene expression of NMDA and GABAA receptors in patients with mesial temporal lobe epilepsy

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Amygdala gene expression of NMDA and GABA_A receptors in patients with mesial temporal lobe epilepsy