Hippocampal ΔFosB expression is associated with cognitive impairment in a subgroup of patients with childhood epilepsies.
Hippocampal ΔFosB expression is associated with cognitive impairment in a subgroup of patients with childhood epilepsies.
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DOI：
10.3389/fneur.2023.1331194
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发表时间：
2023
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
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癫痫是一种以反复发作为特征的慢性神经系统疾病，通常与其他神经系统和神经退行性疾病共病，如阿尔茨海默病（AD）。反复发作的患者通常表现为认知障碍。然而，目前还不清楚癫痫发作，即使是不频繁的，如何产生长期的认知缺陷。一种机制可能是尿素诱导的ΔFosB表达，ΔFosB是一种持久调节可塑性相关基因表达并驱动认知功能障碍的长寿命转录因子。我们之前发现，与认知功能正常的受试者相比，轻度认知障碍（MCI）和AD患者海马齿状回（DG）中ΔFosB的活性依赖性表达增加。在MCI患者中，较高的ΔFosB表达对应于较低的简易精神状态检查评分。从颞叶癫痫患者手术切除的DG组织也显示出强烈的ΔFosB表达;然而，目前尚不清楚ΔFosB表达是否也对应于非AD相关癫痫的认知功能障碍。为了测试DG ΔFosB表达是否指示不同病因的癫痫患者的认知障碍，我们评估了33例儿童癫痫患者的海马组织中ΔFosB的表达，这些患者在手术前接受了儿童韦氏智力量表（WISC）测试。我们发现，在轻度至重度智力残疾（FSIQ < 85）患者中，ΔFosB表达与全面智商（FSIQ）呈负相关。我们的数据表明，ΔFosB表达对应于不同病因的癫痫患者的认知障碍，支持ΔFosB可能在表观遗传学上调节基因表达并损害广泛的癫痫综合征的认知的假设。
Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is often comorbid with other neurological and neurodegenerative diseases, such as Alzheimer's disease (AD). Patients with recurrent seizures often present with cognitive impairment. However, it is unclear how seizures, even when infrequent, produce long-lasting deficits in cognition. One mechanism may be seizure-induced expression of ΔFosB, a long-lived transcription factor that persistently regulates expression of plasticity-related genes and drives cognitive dysfunction. We previously found that, compared with cognitively-intact subjects, the activity-dependent expression of ΔFosB in the hippocampal dentate gyrus (DG) was increased in individuals with mild cognitive impairment (MCI) and in individuals with AD. In MCI patients, higher ΔFosB expression corresponded to lower Mini-Mental State Examination scores. Surgically resected DG tissue from patients with temporal lobe epilepsy also showed robust ΔFosB expression; however, it is unclear whether ΔFosB expression also corresponds to cognitive dysfunction in non-AD-related epilepsy. To test whether DG ΔFosB expression is indicative of cognitive impairment in epilepsies with different etiologies, we assessed ΔFosB expression in surgically-resected hippocampal tissue from 33 patients with childhood epilepsies who had undergone Wechsler Intelligence Scale for Children (WISC) testing prior to surgery. We found that ΔFosB expression is inversely correlated with Full-Scale Intelligence Quotient (FSIQ) in patients with mild to severe intellectual disability (FSIQ < 85). Our data indicate that ΔFosB expression corresponds to cognitive impairment in epilepsies with different etiologies, supporting the hypothesis that ΔFosB may epigenetically regulate gene expression and impair cognition across a wide range of epilepsy syndromes.
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影响因子：
2.7
作者：
Crino, Peter B.
通讯作者：
Crino, Peter B.
影响因子：
38.1
作者：
Bell, Brian;Lin, Jack J.;Seidenberg, Michael;Hermann, Bruce
通讯作者：
Hermann, Bruce
影响因子：
5.4
作者：
Buckley, Ashura W.;Holmes, Gregory L.
通讯作者：
Holmes, Gregory L.
影响因子：
7.2
作者：
Barrouillet, Pierre;Camos, Valerie
通讯作者：
Camos, Valerie
DOI：
10.1684/epd.2015.0739
发表时间：
2015-06
期刊：
Epileptic disorders : international epilepsy journal with videotape
影响因子：
--
作者：
Holmes GL
通讯作者：
Holmes GL