Dysregulation of miR-146a: a causative factor in epilepsy pathogenesis, diagnosis, and prognosis

Mao, Shiqi; Wu, Jinhan; Yan, Jingkai; Zhang, Weijun; Zhu, Feng

doi:10.3389/fneur.2023.1094709

Cited by 6 publications

(7 citation statements)

References 71 publications

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“…Inflammation is also reduced by many miRNAs, including miR-34c-5p, miR-93, miR-124, and others [112][113][114][115][116]. Chronic neuroinflammation has been linked to the development of neurodegenerative illnesses such as epilepsy, Amyotrophic Lateral Sclerosis (ASL), Parkinson's Disease (PD), and Alzheimer's Disease (AD) [108,[117][118][119][120][121].…”

Section: Figurementioning

confidence: 99%

“…The genetic etiology of epilepsy is still controversial [149]. The underlying pathogenesis involved in epilepsy include ion channel dysfunction, synaptic remodeling, gliosis, and neuronal death [117,144]. Genetics influence ~70% of epilepsy cases, while acquired and environmental factors, such as traumatic injury and infections of the brain account for the remainder of cases.…”

Section: Genetic Etiologymentioning

confidence: 99%

“…Neuroinflammation is another significant contributor to the pathogenesis of epilepsy, particularly temporal lobe epilepsy, which is the most common cause of partial seizures and the primary source of refractory seizures [117][118][119]. Stimulation of pro-inflammatory molecules such as IL-1β, IL-6, TNF-ɑ, and TLRs induces neurological modifications that result in impaired integrity of the blood brain barrier, neuronal loss, and hyperexcitotoxicity.…”

Section: Immune Etiologymentioning

confidence: 99%

“…Following a seizure, activated TLR4 triggers proinflammatory NFκB signaling and up-regulation of IL-1, IFN-α, and miR-146a. The increase in miR146a levels dampens NFκB activity, reducing IL-1 and IFN-α production, resulting in mitigated inflammatory responses post-seizure [117,150]. Tao et al used a lithium-pilocarpine mouse model to evaluate whether intranasal delivery of miR-146a mimics could delay seizure onset of terminal lobe epilepsy [118].…”

Section: Mechanistic Basis For Mirna-based Epilepsy Therapiesmentioning

confidence: 99%

“…Fortunately, using a lithium-pilocarpine rat model that mimics mesial temporal lobe epilepsy (MTLE), Ashhab et al, found an intricate connection between TNF-α expression and miR-155 levels [163]. In children with chronic TLE, the expression levels of both miR-155 and the pro-inflammatory cytokine TNF-α are increased [117]. Furthermore, in cultured hippocampal astrocytes, LPS treatment or activation of MRP8 resulted in elevated levels of both miR-155 and TNF-α.…”

Section: The Development Of Genetically Modified Mirna Animal Models ...mentioning

confidence: 99%

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Non-coding RNAs and neuroinflammation: implications for neurological disorders

Chen,

Mateski,

Gerace

et al. 2024

Exp. Biol. Med.

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Neuroinflammation is considered a balanced inflammatory response important in the intrinsic repair process after injury or infection. Under chronic states of disease, injury, or infection, persistent neuroinflammation results in a heightened presence of cytokines, chemokines, and reactive oxygen species that result in tissue damage. In the CNS, the surrounding microglia normally contain macrophages and other innate immune cells that perform active immune surveillance. The resulting cytokines produced by these macrophages affect the growth, development, and responsiveness of the microglia present in both white and gray matter regions of the CNS. Controlling the levels of these cytokines ultimately improves neurocognitive function and results in the repair of lesions associated with neurologic disease. MicroRNAs (miRNAs) are master regulators of the genome and subsequently control the activity of inflammatory responses crucial in sustaining a robust and acute immunological response towards an acute infection while dampening pathways that result in heightened levels of cytokines and chemokines associated with chronic neuroinflammation. Numerous reports have directly implicated miRNAs in controlling the abundance and activity of interleukins, TGF-B, NF-kB, and toll-like receptor-signaling intrinsically linked with the development of neurological disorders such as Parkinson’s, ALS, epilepsy, Alzheimer’s, and neuromuscular degeneration. This review is focused on discussing the role miRNAs play in regulating or initiating these chronic neurological states, many of which maintain the level and/or activity of neuron-specific secondary messengers. Dysregulated miRNAs present in the microglia, astrocytes, oligodendrocytes, and epididymal cells, contribute to an overall glial-specific inflammatory niche that impacts the activity of neuronal conductivity, signaling action potentials, neurotransmitter robustness, neuron-neuron specific communication, and neuron-muscular connections. Understanding which miRNAs regulate microglial activation is a crucial step forward in developing non-coding RNA-based therapeutics to treat and potentially correct the behavioral and cognitive deficits typically found in patients suffering from chronic neuroinflammation.

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Section: Figurementioning

confidence: 99%

Section: Genetic Etiologymentioning

confidence: 99%

Section: Immune Etiologymentioning

confidence: 99%

Section: Mechanistic Basis For Mirna-based Epilepsy Therapiesmentioning

confidence: 99%

Section: The Development Of Genetically Modified Mirna Animal Models ...mentioning

confidence: 99%

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Non-coding RNAs and neuroinflammation: implications for neurological disorders

Chen,

Mateski,

Gerace

et al. 2024

Exp. Biol. Med.

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Metformin improves diabetic neuropathy by reducing inflammation through up-regulating the expression of miR-146a and suppressing oxidative stress

Liu,

You,

Yang

et al. 2024

Journal of Diabetes and its Complications

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Diagnostic Panel of Three Genetic Biomarkers Based on Artificial Neural Network for Patients With Idiopathic Generalized Epilepsy

Yabacı Tak,

Tak,

Ilgen Uslu

et al. 2024

Acta Neurologica Scandinavica

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The aim of this study is to evaluate the utility of an artificial neural network (ANN) model in diagnosing idiopathic generalized epilepsy (IGE) and to compare the results of the diagnostic model constructed by combining the expression levels of miR‐146a, miR‐155, and miR‐132 genes using ANN, random forest (RF), and discriminant analysis (DA). qRT‐PCR is employed to determine the expression levels of the three miRNA genes. Forty‐six IGE patients and 51 healthy controls were included in the study. Three genetic biomarkers were employed to assess the discriminative power of the disease, and they were combined using ANN. Additionally, the performance of ANN was compared with RF and DA. Compared to healthy controls, the miR‐132 gene was significantly higher (p < 0.001) and the miR‐155 and miR‐146a genes were significantly lower in IGE patients (p < 0.001). The area under the curve (AUC) for predictions made by the ANN, RF, and DA were 0.96, 0.87, and 0.75, respectively, with accuracy rates of 0.96, 0.88, and 0.76, respectively. We demonstrate that ANN exhibits the highest accuracy, AUC, sensitivity, and specificity values among the three methods. The obtained results indicate that the combination of the three genes used as markers in IGE plays a significant role in the diagnosis of the disease. Instead of assessing biomarkers individually for the disease, combining them using machine learning methods leads to improved model performance. Additionally, not relying on a single genetic biomarker for the disease enables discrimination based on the collective impact of all biomarkers.

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Dysregulation of miR-146a: a causative factor in epilepsy pathogenesis, diagnosis, and prognosis

Cited by 6 publications

References 71 publications

Non-coding RNAs and neuroinflammation: implications for neurological disorders

Non-coding RNAs and neuroinflammation: implications for neurological disorders

Metformin improves diabetic neuropathy by reducing inflammation through up-regulating the expression of miR-146a and suppressing oxidative stress

Diagnostic Panel of Three Genetic Biomarkers Based on Artificial Neural Network for Patients With Idiopathic Generalized Epilepsy

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