Alterations in hippocampal and cortical densities of functionally different interneurons in rat models of absence epilepsy

Papp, Péter; Kovács, Zsolt; Szocsics, Péter; Juhász, Gábor; Maglóczky, Zsófia

doi:10.1016/j.eplepsyres.2018.05.013

Cited by 19 publications

(23 citation statements)

References 64 publications

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“…1D) and the known role of PV+ and SOM+ interneurons in gamma oscillation generation (Buzsáki et al 1983;Traub et al 1996;Mann et al 2005;Cardin et al 2009;Sohal et al 2009;Veit et al 2017), we hypothesized that GAERS could present a layer-specific increase of interneurons density, especially of PV+ or SOM+ cells. Recent studies indicated modifications of GABAergic interneurons densities in models of genetic epilepsy that further support our hypothesis (Wimmer et al 2015;Papp et al 2018). NeuN staining for neurons did not show significant difference in neuronal density between GAERS and Wistar controls ( Fig.…”

Section: Inhibitory Interneurons Are Increased In the S1bf Of Gaerssupporting

confidence: 83%

“…; Papp et al . ). NeuN staining for neurons did not show significant difference in neuronal density between GAERS and Wistar controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…By contrast, another recent study showed an elevation of PV+ interneurons in the S1 cortex of GAERS that was not present in WAG/Rij (Papp et al . ). As was suggested, this could reflect the difference in epileptogenesis time‐course between the two models of AE: because SWDs appear later in WAG/Rij (3 months vs .…”

Section: Discussionmentioning

confidence: 97%

“…A recent study showed no difference in terms of GABA+ interneurons in the S1Bf of GAERS (Bombardi et al 2018). By contrast, another recent study showed an elevation of PV+ interneurons in the S1 cortex of GAERS that was not present in WAG/Rij (Papp et al 2018). As was suggested, this could reflect the difference in epileptogenesis time-course between the two models of AE: because SWDs appear later in WAG/Rij (3 months vs. 3 weeks in GAERS) (Jarre et al 2017), the increase of PV+ cells in GAERS could result from the repetition of SWDs.…”

Section: Potential Role Of Gabaergic Inhibition In Sensory Impairmentmentioning

confidence: 88%

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Sensory coding is impaired in rat absence epilepsy

Studer

Laghouati

Jarre

et al. 2019

The Journal of Physiology

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Key points Absence epilepsy is characterized by the occurrence of spike‐and‐wave discharges concomitant with an alteration of consciousness and is associated with cognitive comorbidities. In a genetic model of absence epilepsy in the rat, the genetic absence epilepsy rat from Strasbourg (GAERS), spike‐and‐wave discharges are shown to be initiated in the barrel field primary somatosensory cortex that codes whisker‐related information, therefore playing an essential role in the interactions of rodents with their environment. Sensory‐information processing is impaired in the epileptic barrel field primary somatosensory cortex of GAERS, with a delayed sensory‐evoked potential and a duplicated neuronal response to whisker stimulation in in vivo extracellular recordings. Yet, GAERS present no defaults of performance in a texture discrimination task, suggesting the existence of a compensatory mechanism within the epileptic neuronal network. The results of the present study indicate that physiological primary functions are processed differently in an epileptic cortical network. Abstract Several neurodevelopmental pathologies are associated with disorganized cortical circuits that may alter primary functions such as sensory processes. In the present study, we investigated whether the function of a cortical area is altered in the seizure onset zone of absence epilepsy, a prototypical form of childhood genetic epilepsy associated with cognitive impairments. We first combined in vivo multichannel electrophysiological recordings and histology to precisely localize the seizure onset zone in the genetic absence epilepsy rat from Strasbourg (GAERS). We then investigated the functionality of this epileptic zone using extracellular silicon probe recordings of sensory‐evoked local field potentials and multi‐unit activity, as well as a behavioural test of texture discrimination. We show that seizures in this model are initiated in the barrel field part of the primary somatosensory cortex and are associated with high‐frequency oscillations. In this cortex, we found an increased density of parvalbumin‐expressing interneurons in layer 5 in GAERS compared to non‐epileptic Wistar rats. Its functional investigation revealed that sensory abilities of GAERS are not affected in a texture‐discrimination task, whereas the intracortical processing of sensory‐evoked information is delayed and duplicated. Altogether, these results suggest that absence seizures are associated with an increase of parvalbumin‐inhibitory neurons, which may promote the functional relationship between epileptic oscillations and high‐frequency activities. Our findings suggest that cortical circuits operate differently in the epileptic onset zone and may adapt to maintain their ability to process highly specialized information.

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Section: Inhibitory Interneurons Are Increased In the S1bf Of Gaerssupporting

confidence: 83%

“…; Papp et al . ). NeuN staining for neurons did not show significant difference in neuronal density between GAERS and Wistar controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Potential Role Of Gabaergic Inhibition In Sensory Impairmentmentioning

confidence: 88%

See 2 more Smart Citations

Sensory coding is impaired in rat absence epilepsy

Studer

Laghouati

Jarre

et al. 2019

The Journal of Physiology

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“…Loss of inhibitory neurons is observed in models of acquired epilepsy including PTE. 26 To determine the effect of blocking RAGE and TLR4 on the preservation of inhibitory neurons, we used immunostaining to GAD67 to label cortical GABAergic interneurons and counted their densities. The density of GAD67+ neurons was significantly lower in the lesion area of undercut mice than in that of sham mice (Figure 6, p < 0.001, UC-NS vs Sham), but was significantly higher in the groups treated with RAGE mAb or TAK242 after undercut than the undercut group treated with saline, even though the density was still lower than in the sham group (Figure 6, p < 0.05 UC-NS vs UC-RAGE mAb or UC-TAK242).…”

Section: Rage-mabortak242treatment Restoredinterneuroninundercutcortexmentioning

confidence: 99%

Blocking receptor for advanced glycation end products (RAGE) or toll‐like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice

et al. 2021

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Objective: Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis. Methods:In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1 week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2 weeks and with continuous video and wireless electroencephalography (EEG) monitoring between 2 and 6 weeks after injury, respectively. Seizure susceptibility after undercut in RAGE knockout mice was also evaluated with the PTZ test. The lesioned cortex was analyzed with immunohistology.Results:Undercut animals treated with RAGE mAb or TAK242 showed significantly higher seizure threshold than saline-treated undercut mice. Consistently, undercut injury in RAGE knockout mice did not cause a reduction in seizure threshold in the PTZ test. EEG and video recordings revealed a significant decrease in the cumulative spontaneous seizure events in the RAGE mAb-or TAK242-treated group (p < 0.001, when the RAGE mAb or TAK242 group is compared with the saline group). The lesioned cortical tissues of RAGE mAbor TAK242-treated undercut group showed higher neuronal densities of Nissl staining and higher densities of glutamic acid decarboxylase 67-immunoreactive interneurons than the saline-treated undercut group. Immunostaining to GFAP and Iba-1 revealed lower densities of astrocytes and microglia in the cortex of the treatment groups, suggesting reduced glia activation.Significance:RAGE and TLR4 signaling are critically involved in posttraumatic epileptogenesis. Blocking these pathways early after traumatic brain injury is a promising strategy for preventing posttraumatic epilepsy.

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Structural changes in the neocortex as correlates of variations in EEG spectra and seizure susceptibility in rat brains with different degrees of dysplasia

Setkowicz

Gzieło

Kielbinski

et al. 2021

J of Comparative Neurology

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Disturbances of the early stages of neurogenesis lead to irreversible changes in the structure of the mature brain and its functional impairment, including increased excitability, which may be the basis for drug‐resistant epilepsy. The range of possible clinical symptoms is as wide as the different stages of disturbed neurogenesis may be. In this study, we used a quadruple model of brain dysplasia by comparing structural and functional disorders in animals whose neurogenesis was disturbed with a single dose of 1 Gy of gamma rays at one of the four stages of neurogenesis, that is, on days 13, 15, 17, or 19 of prenatal development. When reached adulthood, the prenatally irradiated rats received EEG teletransmitter implantation. Thereafter, pilocarpine was administered and significant differences in susceptibility to seizure behavioral symptoms were detected depending on the degree of brain dysplasia. Before, during, and after the seizures significant correlations were found between the density of parvalbumin‐immunopositive neurons located in the cerebral cortex and the intensity of behavioral seizure symptoms or increases in the power of particular EEG bands. Neurons expressing calretinin or NPY showed also dysplasia‐related increases without, however, correlations with parameters of seizure intensity. The results point to significant roles of parvalbumin‐expressing interneurons, and also to expression of NPY—an endogenous anticonvulsant and neuroprotectant reducing susceptibility to seizures and supporting neuronal survival.

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Alterations in hippocampal and cortical densities of functionally different interneurons in rat models of absence epilepsy

Cited by 19 publications

References 64 publications

Sensory coding is impaired in rat absence epilepsy

Sensory coding is impaired in rat absence epilepsy

Blocking receptor for advanced glycation end products (RAGE) or toll‐like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice

Structural changes in the neocortex as correlates of variations in EEG spectra and seizure susceptibility in rat brains with different degrees of dysplasia

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