Kcnj6 (GIRK2) trisomy is not sufficient for conferring the susceptibility to infantile spasms seen in the Ts65Dn mouse model of down syndrome

Joshi, Krutika; Shen, Lily; Cao, Fan; Dong, Susan; Jia, Zhengping; Cortez, Miguel A.; Snead, O. Carter

doi:10.1016/j.eplepsyres.2018.06.006

Cited by 12 publications

(7 citation statements)

References 26 publications

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“…In the detriplicated model, GIRK2 levels were reduced in the cortex, thalamus, hippocampus, and brainstem relative to the Ts65Dn mice (and comparable to the levels in wild‐type mice) 42 . However, isolated triplication of GIRK2 in wild‐type mice did not lead to spasms or abnormal EEG findings, suggesting that GIRK2 overexpression is necessary, but not sufficient, for epileptic spasms 43 …”

Section: Resultsmentioning

confidence: 88%

Epileptic spasms in individuals with Down syndrome: A review of the current literature

2020

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Epilepsy can occur in individuals with Down syndrome (DS), with epileptic spasms representing the most frequent seizure type in this population. Epileptic spasms can have devastating consequences on the development of individuals with the condition. This review sought to explore the lifetime prevalence and underlying mechanism of epileptic spasms in this population. We also aimed to review the response rate to various treatments, the relapse rate, and the development of subsequent epilepsy or autism in this population. A comprehensive literature search was conducted for articles discussing the lifetime prevalence, diagnosis, treatment, outcomes, or underlying etiology of epileptic spasms in animal models or individuals with DS. According to available literature, the global clinic‐based lifetime prevalence of epilepsy in individuals with DS ranged from 1.6% to 23.1%, with epileptic spasms representing 6.7%‐66.7% of these cases. Response rate to treatment with adrenocorticotropic hormone/corticosteroids was highest (81%) and has the most literature supporting its use, with other regimens, including vigabatrin and other antiepileptic drugs, having lower response rates. Epileptic spasms occur more frequently in children with DS than in the general population, though more studies are needed to determine the true lifetime prevalence of epileptic spasms in this population. Generally, children with DS and epileptic spasms tend to be more responsive to treatment and have better outcomes than children with epileptic spasms of unknown etiology (ie, without DS), in terms of response and relapse rates as well as the development of intractable epilepsy (eg, Lennox‐Gastaut syndrome).

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Section: Resultsmentioning

confidence: 88%

Epileptic spasms in individuals with Down syndrome: A review of the current literature

2020

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“…EEG activity was recorded in freely-moving animals for 90 min using a Grass amplifier and software (Grass Instruments) and monitored by a videorecorder. Mice were placed in warm Plexiglas chambers (Harvard Apparatus) for 1-h acclimation period (Joshi et al, 2018). Brains were harvested to verify electrode placement.…”

Section: Electroencephalogram (Eeg) Studiesmentioning

confidence: 99%

The γ-Protocadherins Regulate the Survival of GABAergic Interneurons during Developmental Cell Death

et al. 2020

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Inhibitory interneurons integrate into developing circuits in specific ratios and distributions. In the neocortex, inhibitory network formation occurs concurrently with the apoptotic elimination of a third of GABAergic interneurons. The cell surface molecules that select interneurons to survive or die are unknown. Here, we report that members of the clustered Protocadherins (cPCDHs) control GABAergic interneuron survival during developmentally-regulated cell death. Conditional deletion of the gene cluster encoding the c-Protocadherins (Pcdhgs) from developing GABAergic neurons in mice of either sex causes a severe loss of inhibitory populations in multiple brain regions and results in neurologic deficits such as seizures. By focusing on the neocortex and the cerebellar cortex, we demonstrate that reductions of inhibitory interneurons result from elevated apoptosis during the critical postnatal period of programmed cell death (PCD). By contrast, cortical interneuron (cIN) populations are not affected by removal of Pcdhgs from pyramidal neurons or glial cells. Interneuron loss correlates with reduced AKT signaling in Pcdhg mutant interneurons, and is rescued by genetic blockade of the pro-apoptotic factor BAX. Together, these findings identify the PCDHGs as pro-survival transmembrane proteins that select inhibitory interneurons for survival and modulate the extent of PCD. We propose that the PCDHGs contribute to the formation of balanced inhibitory networks by controlling the size of GABAergic interneuron populations in the developing brain.

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“…However, another paper assumed that Kir3.2 overexpression was not sufficient to sensitize the GABA B receptor agonist-induced IS phenotype in the Ts65Dn mouse model of DS (Joshi et al, 2018).…”

Section: Girk Channels Possess a Mechanism Of Inward Rectificationmentioning

confidence: 99%

Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy

Akyüz

Köklü

Uner

et al. 2021

J of Neuroscience Research

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Epilepsy is a neurological disease characterized by two spontaneous seizures occurring within 24 hr, or two spontaneous seizures within 10 years after an unprovoked seizure (Fisher et al., 2014). The disease occurs by an increased tendency to generate seizures attributed to abnormal brain activity, caused by the disruption of the dynamic excitatory and inhibitory neuronal balance in the central nervous system (CNS) (Navidhamidi et al., 2017). Aberrant connectivity between neuronal networks may result in pathologically synchronized discharges and subsequently recurrent seizures (Aronica & Muhlebner, 2017). Epilepsy not only poses a significant burden on the patients and their families, but is also associated with significant social, behavioral, and economic effects (Tatum et al., 2009).Epilepsy affects people of all ages and has emerged as a global health concern affecting more than 70 million patients worldwide.Despite the recent advances in pre-clinical and clinical research, the

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Kcnj6 (GIRK2) trisomy is not sufficient for conferring the susceptibility to infantile spasms seen in the Ts65Dn mouse model of down syndrome

Cited by 12 publications

References 26 publications

Epileptic spasms in individuals with Down syndrome: A review of the current literature

Epileptic spasms in individuals with Down syndrome: A review of the current literature

The γ-Protocadherins Regulate the Survival of GABAergic Interneurons during Developmental Cell Death

Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy

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