Febrile Seizure-Related miR-148a-3p Exerts Neuroprotection by Promoting the Proliferation of Hippocampal Neurons in Children with Temporal Lobe Epilepsy

Abstract

Temporal lobe epilepsy (TLE) is the most common epilepsy in both adult and children. Some microRNAs (miRNAs) are abnormally expressed in neurological diseases. This study aimed to investigate the expression level and clinical significance of miR-148a-3p in TLE children and explore its effect on the biological viability of hippocampal neurons. The expression level of miR-148a-3p in the serum of TLE children was examined using quantitative real-time PCR. A receiver operating characteristic curve was plotted to determine the diagnostic accuracy of miR-148a-3p in TLE. Hippocampal neurons were cultured in magnesium-free medium to construct a TLE cell model. The effects of miR-148a-3p on hippocampal neuronal viability and apoptosis rate were detected by MTT and flow cytometry, respectively. miR-148a-3p was overexpressed and correlated with seizure frequency and febrile seizure (FS) history in TLE children. miR-148a-3p was of great value in the diagnosis of TLE, and it can be used to distinguish cases with FS history. Hippocampal neurons treated with magnesium-free medium were used as an in vitro model of TLE and showed significantly increased miR-148a-3p, decreased cell viability, and increased cell apoptosis, while these changes were eliminated markedly by miR-148a-3p knockdown. miR-148a-3p is overexpressed and associated with seizure frequency and FS history and serves as a novel diagnostic biomarker in TLE. In addition, the downregulation of miR-148a-3p exerts neuroprotective role by improving hippocampal neuronal cell viability. miR-148a-3p may provide new ideas for the treatment and diagnosis of TLE.

Human Milk Extracellular Vesicles: A Biological System with Clinical Implications

“…Recently, Ting et al [ 103 ] conducted a systematic review on miRNAs in human milk and reported miR-148a-3p, miR-30a/d-5p, let-7a/b/f-5p, miR-22-3p, miR-146b-5p, and miR-200a/c-3p to be the top 10 highly abundant miRNAs in all human milk fractions including hMEVs. Note that miR-148a-3p is the most abundant miRNA in hMEVs, and is involved in multiple cellular processes, including regulating DNMT1-dependent DNA methylation [ 105 , 106 , 107 ], suppressing tumor growth and metastasis [ 106 , 107 , 108 , 109 , 110 , 111 ], mitigating NF-κB mediated intestinal inflammation [ 112 ], modulating angiogenesis [ 113 , 114 ], and exerting neuroprotective effect [ 115 , 116 , 117 , 118 , 119 ]. Thus, hMEV miRNAs exhibit a wide array of functions in both normal biology and disease, and warrant further study.…”

“…Direct effects of hMEVs on neurodevelopment remain to be demonstrated. However, promising associations were observed between miR-148a-3p (the most abundant hMEV-derived miRNA) and neuroprotection in Alzheimer’s Disease [ 115 , 116 ], ischemic stroke [ 117 ], and temporal lobe epilepsy [ 118 ]. In both term and preterm infants, human milk feeding is associated with improved neurodevelopmental outcomes [ 157 , 158 ].…”

“…The significance of the relationship between hMEV-derived miR-148a and infant anthropometric measures diminished at 3 to 6 months of lactation [ 79 ]. MiR-148a is the precursor of miR-148a-3p, the most abundant miRNA in hMEVs, which has known neuroprotective and neuro-proliferative effects [ 103 , 115 , 116 , 117 , 118 ]. Accordingly, the reduction of hMEV-derived miR-148a in maternal overweight/obesity provides some mechanistic insight into increased risk of childhood obesity and unfavorable neurodevelopmental outcomes in obese mothers.…”

Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus

“…Overexpression of miR-148a-3p in a febrile seizure (FS) model group affected the neuroimmune system and neuronal apoptosis in a previous study [ 34 ]. miR-148a-3p may serve as a novel diagnostic biomarker for TLE [ 35 ]. In our study, we found that miR-148a was downregulated in the DG region on days 14 and 60 post-SE.…”

Prenatal SARS-CoV-2 infection alters postpartum human milk-derived extracellular vesicles

“…Noted that miR-148a is the most abundance HMEV-derived microRNA, 11,58 influencing various functions, including DNA methylation through DNA methyltransferase 1, 59 cell and tissue development, 60 inflammation, 61,62 and neuroprotection. 63,64 Also, miR-146a-5p is known to regulate type I interferon signaling 65,66 and involved in cellular responses upon viral infection. 67,68 Taken together, our findings demonstrate that prenatal SARS-CoV-2 infection (1-6 months before delivery) does have post-acute infection effects on HMEV-derived proteins, but not miRNAs, at 2-week of lactation.…”