Altered expression of KCC2 in GABAergic interneuron contributes prenatal stress-induced epileptic spasms in infant rat

Baek, Hyunjung; Yi, Min‐Hee; Pandit, Sudip; Park, Jin Bong; Kwon, Hyeok Hee; Zhang, Enji; Kim, Se-Na; Shin, Nara; Kim, Eunjee; Lee, Young Ho; Kim, Yonghyun; Kim, Dong Ho; Kang, Joon Won

doi:10.1016/j.neuint.2016.05.006

Cited by 18 publications

(23 citation statements)

References 39 publications

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“…The critical balance between excitation and inhibition in the brain is maintained by two major classes of neurons: excitatory projection neurons and inhibitory local circuit interneurons . GABA primarily mediates inhibition; thus, GABAergic interneuron function has been associated with many neurodevelopmental and neurodegenerative disorders such as ASDs, schizophrenia, and epilepsy . Many lncRNAs, including Gtl2, Rian, Evf2, Copg2as, Dlx6‐AS1 and others, have been reported to participate in the regulation of GABAergic interneuron functions .…”

Section: Lncrnas In the Central Nervous System (Cns) And Brainmentioning

confidence: 99%

“…64 GABA primarily mediates inhibition; thus, GABAergic interneuron function has been associated with many neurodevelopmental and neurodegenerative disorders such as ASDs, schizophrenia, and epilepsy. [65][66][67] Many lncRNAs, including Gtl2, Rian, Evf2, Copg2as, Dlx6-AS1 and others, have been reported to participate in the regulation of GABAergic interneuron functions. 68,69 Evf2 is transcribed from the Dlx-5/6 ultraconserved region that recruits the transcription factors DLX and MECP2, which affect Dlx-5/6 enhancer activities via both cis-and trans-mechanisms.…”

Section: Lncrnas In the Central Nervous System (Cns) And Brainmentioning

confidence: 99%

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Long noncoding RNA and its contribution to autism spectrum disorders

Jing

Yang

2017

CNS Neurosci Ther

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Recent studies have indicated that long noncoding RNAs (lncRNAs) play important roles in multiple processes, such as epigenetic regulation, gene expression regulation, development, nutrition-related and other diseases, toxic response, and response to drugs. Although the functional roles and mechanisms of several lncRNAs have been discovered, a better understanding of the vast majority of lncRNAs remains elusive. To understand the functional roles and mechanisms of lncRNAs is critical because these transcripts represent the majority of the transcriptional output of the mammalian genome. Recent studies have also suggested that lncRNAs are more abundant in the human brain and are involved in neurodevelopment and neurodevelopmental disorders, including autism spectrum disorders (ASDs). In this study, we review several known functions of lncRNAs and the potential contribution of lncRNAs to ASDs and to other genetic syndromes that have a similar clinical presentation to ASDs, such as fragile X syndrome and Rett syndrome.

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Section: Lncrnas In the Central Nervous System (Cns) And Brainmentioning

confidence: 99%

Section: Lncrnas In the Central Nervous System (Cns) And Brainmentioning

confidence: 99%

Long noncoding RNA and its contribution to autism spectrum disorders

Jing

Yang

2017

CNS Neurosci Ther

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“…However, by exposing rats to prenatal stress (betamethasone injection into the dams), NMDA-induced spasms in the postnatal animals became responsive to ACTH [67]. Prenatal acute immobilization stress or forced cold water swim stress also sensitized rat pups to NMDA-induced spasms, possibly by downregulating GABAergic systems and decreasing the expression of the potassium-chloride co-transporter 2 (KCC2) [56,68]. KCC2 is mainly responsible for establishing the chloride gradient by keeping intracellular chloride concentration low, so KCC2 reduction favors less hyperpolarization during GABAergic neurotransmission (and, hence, increased seizure propensity) [69].…”

Section: Increased Glutamate Receptor Activation: Prenatal Stress/nmdmentioning

confidence: 99%

Infantile Spasms: An Update on Pre-Clinical Models and EEG Mechanisms

Janicot¹,

Shao²,

Stafstrom³

2020

Children

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Infantile spasms (IS) is an epileptic encephalopathy with unique clinical and electrographic features, which affects children in the middle of the first year of life. The pathophysiology of IS remains incompletely understood, despite the heterogeneity of IS etiologies, more than 200 of which are known. In particular, the neurobiological basis of why multiple etiologies converge to a relatively similar clinical presentation has defied explanation. Treatment options for this form of epilepsy, which has been described as “catastrophic” because of the poor cognitive, developmental, and epileptic prognosis, are limited and not fully effective. Until the pathophysiology of IS is better clarified, novel treatments will not be forthcoming, and preclinical (animal) models are essential for advancing this knowledge. Here, we review preclinical IS models, update information regarding already existing models, describe some novel models, and discuss exciting new data that promises to advance understanding of the cellular mechanisms underlying the specific EEG changes seen in IS—interictal hypsarrhythmia and ictal electrodecrement.

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“…Numerous neuropsychiatric disorders are known to be caused by the dysfunction of the gamma-aminobutyric acid (GABA)ergic signaling system, including, autism spectrum disorder, 5) schizophrenia, 6) and epilepsy. 7 8) The excitatory/inhibitory shift is interrupted during cerebral development due to prenatal stress and this may result in an increased susceptibility to spasms. Baek et al 8) have previously demonstrated that prenatal exposure to acute immobilization stress (AIS) leads to increased susceptibility to IS.…”

Section: Introductionmentioning

confidence: 99%

“… 7 8) The excitatory/inhibitory shift is interrupted during cerebral development due to prenatal stress and this may result in an increased susceptibility to spasms. Baek et al 8) have previously demonstrated that prenatal exposure to acute immobilization stress (AIS) leads to increased susceptibility to IS. However, considering the diversity of stress, different responses may be expected depending on the degree of stress.…”

Section: Introductionmentioning

confidence: 99%

Long-term prenatal stress increases susceptibility of N-methyl-D-aspartic acid-induced spasms in infant rats

et al. 2018

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PurposeInfantile spasms, also known as West syndrome, is an age-specific epileptic seizure. Most patients with this condition also exhibit delayed development. This study aimed to determine the effect of long-term prenatal stress on susceptibility to infantile spasms.MethodsWe subjected pregnant rats to acute or chronic immobilization stress. Resulting offspring received N-methyl-D-aspartic acid (15 mg/kg, intraperitoneally) on postnatal day 15, and their behaviors were observed 75 minutes after injection. The expression of KCC2 and GAD67 was also determined using immunohistochemistry.ResultsExposure to long-term prenatal stress increased the frequency of spasms and decreased the latency to onset of spasms compared with offspring exposed to short-term prenatal stress. Expression of KCC2 and GAD67 also decreased in the group exposed to long-term prenatal stress compared with the group exposed to short-term prenatal stress.ConclusionOur study suggests that exposure to long-term prenatal stress results in increased susceptibility to seizures.

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Altered expression of KCC2 in GABAergic interneuron contributes prenatal stress-induced epileptic spasms in infant rat

Cited by 18 publications

References 39 publications

Long noncoding RNA and its contribution to autism spectrum disorders

Long noncoding RNA and its contribution to autism spectrum disorders

Infantile Spasms: An Update on Pre-Clinical Models and EEG Mechanisms

Long-term prenatal stress increases susceptibility of N-methyl-D-aspartic acid-induced spasms in infant rats

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