Abstract:Temporal lobe epilepsy (TLE) is a severe neurological disorder accompanied by recurrent spontaneous seizures. Although the knowledge of TLE onset is still incomplete, TLE pathogenesis most likely involves the aberrant expression of microRNAs (miRNAs). miRNAs play an essential role in organism homeostasis and are widely studied in TLE as potential therapeutics and biomarkers. However, many discrepancies in discovered miRNAs occur among TLE studies due to model-specific miRNA expression, different onset ages of … Show more
“…Furthermore, multiple miRNAs showed altered expression in both adulthood and infantile-onset epilepsy (DESeq2: 16; limma: 17). The sequencing results of the chronic stage (of both infantile- and adult-onset TLE) were described in our publication addressing the epilepsy onset age impact on miRNA expression in chronic epilepsy in human and rat 10 . Figure 2 Expression changes of all miRNAs detected in adult and infantile-onset of epileptogenesis.…”
Section: Resultsmentioning
confidence: 99%
“…Interestingly, all miRNAs but miR-132-5p were downregulated 24 h after SE induced in P12, suggesting different mechanisms involved in the acute response to SE in the immature brain. In our recent study, we have shown that chronic miRNA profile depends on the epilepsy onset age in both rats and humans, while the adult-onset epilepsy model shows greater overlap with patients with refractory epilepsy compared with the infantile-one 10 .…”
Temporal lobe epilepsy (TLE) is the most common epilepsy type. TLE onset in infancy aggravates features like severity, drug responsiveness, or development of comorbidities. These aggravations may arise from altered micro RNA (miRNA) expression specific to the early onset of the disease. Although the miRNA involvement in TLE is widely studied, the relationship between the onset-age and miRNA expression has not been addressed. Here, we investigated the miRNA profile of infantile and adult-onset TLE in rats combining sequencing and PCR. Since miRNA expression changes with the disease progression, we scrutinized miRNA dynamics across three stages: acute, latent, and chronic. We report that infantile-onset TLE leads to changes in the expression of fewer miRNAs across these stages. Interestingly, the miRNA profile in the acute stage of infantile-onset TLE overlaps in dysregulation of miR-132-5p, -205, and -211-3p with the chronic stage of the disease starting in adulthood. The analysis of putative targets linked the majority of dysregulated miRNAs with pathways involved in epilepsy. Our profiling uncovered miRNA expression characteristic for infantile and adulthood-onset epileptogenesis, suggesting the distinct biology underlying TLE in the onset age-dependent matter. Our results indicate the necessity of addressing the onset age as an important parameter in future epilepsy research.
“…Furthermore, multiple miRNAs showed altered expression in both adulthood and infantile-onset epilepsy (DESeq2: 16; limma: 17). The sequencing results of the chronic stage (of both infantile- and adult-onset TLE) were described in our publication addressing the epilepsy onset age impact on miRNA expression in chronic epilepsy in human and rat 10 . Figure 2 Expression changes of all miRNAs detected in adult and infantile-onset of epileptogenesis.…”
Section: Resultsmentioning
confidence: 99%
“…Interestingly, all miRNAs but miR-132-5p were downregulated 24 h after SE induced in P12, suggesting different mechanisms involved in the acute response to SE in the immature brain. In our recent study, we have shown that chronic miRNA profile depends on the epilepsy onset age in both rats and humans, while the adult-onset epilepsy model shows greater overlap with patients with refractory epilepsy compared with the infantile-one 10 .…”
Temporal lobe epilepsy (TLE) is the most common epilepsy type. TLE onset in infancy aggravates features like severity, drug responsiveness, or development of comorbidities. These aggravations may arise from altered micro RNA (miRNA) expression specific to the early onset of the disease. Although the miRNA involvement in TLE is widely studied, the relationship between the onset-age and miRNA expression has not been addressed. Here, we investigated the miRNA profile of infantile and adult-onset TLE in rats combining sequencing and PCR. Since miRNA expression changes with the disease progression, we scrutinized miRNA dynamics across three stages: acute, latent, and chronic. We report that infantile-onset TLE leads to changes in the expression of fewer miRNAs across these stages. Interestingly, the miRNA profile in the acute stage of infantile-onset TLE overlaps in dysregulation of miR-132-5p, -205, and -211-3p with the chronic stage of the disease starting in adulthood. The analysis of putative targets linked the majority of dysregulated miRNAs with pathways involved in epilepsy. Our profiling uncovered miRNA expression characteristic for infantile and adulthood-onset epileptogenesis, suggesting the distinct biology underlying TLE in the onset age-dependent matter. Our results indicate the necessity of addressing the onset age as an important parameter in future epilepsy research.
“…Interestingly, our data revealed that some microRNAs are exclusively increased in the younger sister who suffers from neurological abnormalities and thus, such microRNAs are likely to be involved in brain function and have potential clinical inference and contributing to the neuropathophysiology of DMD. Such microRNAs were associated with some neurological disorders, for instance miR-539-5p was upregulated in serum of this particular carrier and was previously reported to be associated with the onset of epilepsy in all patients' age categories (55). Zacharewicz et al revealed that miR-539 were regulated with age and exercise and were predicted to influence Akt-mTOR signaling, and therefore controlling skeletal muscle mass (56).…”
Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder that occurs due to inactivating mutations in DMD gene, leading to muscular dystrophy. Prediction of pathological complications of DMD and the identification of female carriers are important research points that aim to reduce disease burden. Herein, we describe a case of a late DMD patient and his immediate female family members, who all carry same DMD mutation and exhibited varied degrees of symptoms. In our study, we sequenced the whole miRNome in leukocytes and plasma of the family members and results were validated using Real-Time PCR. Our results highlighted the role of miR-409-3p, miR-424-5p, miR-144-3p as microRNAs that show correlation with the extent of severity of muscular weakness and can be used for detection of asymptomatic carriers. Cellular and circulating levels of miR-494-3p had showed significant increase in symptomatic carriers, which may indicate significant roles played by this miRNA in the onset of muscular weakness. Interestingly, circulating levels of miR-206 and miR-410-3p were significantly increased only in the severely symptomatic carrier. In conclusion, our study highlighted several miRNA species, which could be used in predicting the onset of muscle and/or neurological complications in DMD carriers.
“…MiRNAs, as a class of noncoding RNA molecules about 20∼24 bp in length, are involved in the regulation of a variety of gene expression and signaling pathways in the body. At present, it has also been confirmed that miRNAs are involved in the regulation of the function of the nervous system, including the development of nerve cells, neuronal apoptosis, and the differentiation of neural stem cells [8].…”
This study was aimed to investigate the changes of brain MRI features and serum biological parameters in patients with TLE. 30 patients with unilateral TLE confirmed by surgical pathology were selected as study subjects, and 30 subjects without a history of epilepsy who underwent health examinations during the same period were selected as controls. The brain MRI features of the patients were explored and the T2 relaxation time (HCT2) indexes of the bilateral hippocampus were extracted. The differences in levels of peripheral blood T lymphocyte subsets, inflammatory cytokines, and miRNAs were measured. The results showed that the hippocampal volume of TLE patients was significantly reduced, and the HCT2 value of the hippocampus was greater than that of the control group (
P
<
0.05
). CD3+ (77.9 ± 4.4)%, CD4+ (45.6 ± 2.2)%, CD8+ (22.1 ± 1.9)%, and CD3+/CD8+ (2.24 ± 0.22) in peripheral blood T lymphocyte subsets of epileptic patients, compared with control group, CD3+, CD4+, and CD4+/CD8+ levels were significantly increased and CD8+ concentration was significantly decreased in epileptic patients (
P
<
0.05
); inflammatory cytokines TNF-α was (2.63 ± 0.26) pg/mL, IL-1β was (4.61 ± 0.57) pg/mL, IL-2 was (1.59 ± 0.21) pg/mL, IL-6 was (2.28 ± 0.19) pg/mL, and ICAM-1 was (1.89 ± 0.30) pg/mL in peripheral blood of epileptic patients, which was significantly increased compared with control group, while IL-10 was significantly decreased in epileptic patients (
P
<
0.05
); miR-146a was (2.14 ± 0.28) and miR-210 was (1.89 ± 0.31), miR-221 (2.44 ± 0.35), miR-34a (0.59 ± 0.14), miR-135b (10.17 ± 0.16), miR-33 (0.26 ± 0.09) in peripheral blood miRNA levels of epileptic patients, and miR-146a, miR-210, miR-221, and miR-34a levels of epileptic patients were significantly increased compared with control group, while MiR-135b and miR-33 levels of epileptic patients were significantly reduced (
P
<
0.05
). In summary, patients with TLE have hippocampal lesions, which may be related to peripheral blood T lymphocyte subsets imbalance, chronic inflammatory response, and abnormal expression of miRNAs.
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