Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model

Lee, Hyoin; Jung, Sang Yong; Lee, Peter Jaehyun; Jeong, Yong Hoon

doi:10.1016/j.expneurol.2017.07.007

Cited by 15 publications

(14 citation statements)

References 44 publications

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“…The acute phase was defined as 1-3 days after SE [19]. The latent phase was defined as a seizure-free period that can last for weeks [20,21]. The chronic phase was defined as the period during which mice exhibited spontaneous, recurrent seizures.…”

Section: Dynamic Changes In Clock Genes In the Hippocampus After Seizuresmentioning

confidence: 99%

Decreased expression of the clock gene Bmal1 is involved in the pathogenesis of temporal lobe epilepsy

Liu

et al. 2021

Mol Brain

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Clock genes not only regulate the circadian rhythm of physiological activities but also participate in the pathogenesis of many diseases. Previous studies have documented the abnormal expression of clock genes in epilepsy. However, the molecular mechanism of brain and muscle Arnt-like protein 1 (Bmal1), one of the core clock genes, in the epileptogenesis and seizures of temporal lobe epilepsy (TLE) remain unclear. We first investigated the levels of Bmal1 and other clock proteins in the hippocampus of subjects with epilepsy to define the function of Bmal1. The levels of Bmal1 were decreased during the latent and chronic phases in the experimental group compared with those in the control group. Knockout of Bmal1 in hippocampal dentate gyrus (DG) neurons of Bmal1flox/flox mice by Synapsin 1 (Syn1) promoter AAV (adeno-associated virus) lowered the threshold of seizures induced by pilocarpine administration. High-throughput sequencing analysis showed that PCDH19 (protocadherin 19), a gene associated with epilepsy, was regulated by Bmal1. PCDH19 expression was also decreased in the hippocampus of epileptic mice. Furthermore, the higher levels of Bmal1 and PCDH19 were detected in patients with no hippocampal sclerosis (no HS) than in patients with HS International League Against Epilepsy (ILAE) type I and III. Altogether, these data suggest that decreased expression of clock gene Bmal1 may participate in epileptogenesis and seizures via PCDH19 in TLE.

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Section: Dynamic Changes In Clock Genes In the Hippocampus After Seizuresmentioning

confidence: 99%

Decreased expression of the clock gene Bmal1 is involved in the pathogenesis of temporal lobe epilepsy

Liu

et al. 2021

Mol Brain

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“…Pilocarpine‐induced SE is followed by a seizure‐free latent period (1–14 days post‐SE), and epileptogenesis develops during this time (Lee, Jung, Lee, & Jeong, ). Previous studies have reported that neuronal circuit alterations occur in the latent period (Vinet et al, ).…”

Section: Discussionmentioning

confidence: 99%

The expression of keratan sulfate reveals a unique subset of microglia in the mouse hippocampus after pilocarpine‐induced status epileptics

Ohgomori

Jinno

2019

J of Comparative Neurology

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Induction of keratan sulfate in microglia has been found in several animal models of neurological disorders. However, the significance of keratan sulfate‐expressing microglia is not fully understood. To address this issue, we analyzed the characteristics of microglia labeled by the 5D4 epitope, a marker of high‐sulfated keratan sulfate, in the mouse hippocampus during the latent period after pilocarpine‐induced status epilepticus (SE). Only 5D4‐negative (5D4−) microglia were found in the CA1 region of vehicle‐treated controls and pilocarpine‐treated mice at 1 day after SE onset. A few 5D4+ microglia appeared in the strata oriens and radiatum at 5 days post‐SE, and they were distributed into the stratum pyramidale at 14 days post‐SE. The expressions of genes related to both anti‐ and pro‐inflammatory cytokines were higher in 5D4+ cells than in 5D4− cells at 5 but not 14 days post‐SE. The expressions of genes related to phagocytosis were higher in 5D4+ cells than in 5D4− cells throughout the latent period. The phagocytic activity of microglia, as measured by engulfment of the zymosan bioparticles, was higher in 5D4+ cells than in 5D4− cells. The contact ratios between excitatory synaptic boutons and microglia were also higher in 5D4+ cells than in 5D4− cells at 5 and 14 days post‐SE. The excitatory/inhibitory ratios of synaptic boutons within the microglial domain were lower in 5D4+ cells than in 5D4− cells at 14 days post‐SE. Our findings indicate that 5D4+ microglia may play some role in epileptogenesis via pruning of excitatory synapses during the latent period after SE.

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“…This view is based on observing varied results from some human and animal studies in which some seizures began almost immediately after the IPI ( Löscher et al, 2015 ). Another thought is that latency is a prerequisite process in epileptogenesis during which changes occurring in the brain, including circuit rewiring, will culminate in the seizures elicited in chronic periods ( Panayiotopoulos, 2005 ; Lee et al, 2017 ). This is based on a traditional view of the stages of epilepsy, whose central gap is the lack of explicit knowledge about brain activity in the absence of seizures.…”

Section: The Latency Controversymentioning

confidence: 99%

Characterizing Hippocampal Oscillatory Signatures Underlying Seizures in Temporal Lobe Epilepsy

Mokhothu

Tanaka

2021

Front. Behav. Neurosci.

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Temporal Lobe Epilepsy (TLE) is a neurological condition characterized by focal brain hyperexcitability, resulting in abnormal neuronal discharge and uncontrollable seizures. The hippocampus, with its inherently highly synchronized firing patterns and relatively high excitability, is prone to epileptic seizures, and it is usually the focus of TLE. Researchers have identified hippocampal high-frequency oscillations (HFOs) as a salient feature in people with TLE and animal models of this disease, arising before or at the onset of the epileptic event. To a certain extent, these pathological HFOs have served as a marker and a potential target for seizure attenuation using electrical or optogenetic interventions. However, many questions remain about whether we can reliably distinguish pathological from non-pathological HFOs and whether they can tell us about the development of the disease. While this would be an arduous task to perform in humans, animal models of TLE provide an excellent opportunity to study the characteristics of HFOs in predicting how epilepsy evolves. This minireview will (1) summarize what we know about the oscillatory disruption in TLE, (2) summarize knowledge about oscillatory changes in the latent period and their role in predicting seizures, and (3) propose future studies essential to uncovering potential treatments based on early detection of pathological HFOs.

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Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model

Cited by 15 publications

References 44 publications

Decreased expression of the clock gene Bmal1 is involved in the pathogenesis of temporal lobe epilepsy

Decreased expression of the clock gene Bmal1 is involved in the pathogenesis of temporal lobe epilepsy

The expression of keratan sulfate reveals a unique subset of microglia in the mouse hippocampus after pilocarpine‐induced status epileptics

Characterizing Hippocampal Oscillatory Signatures Underlying Seizures in Temporal Lobe Epilepsy

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