MiR-135a-5p Is Critical for Exercise-Induced Adult Neurogenesis

Pons-Espinal, Meritxell; Gasperini, Caterina; Marzi, Matteo Jacopo; Braccia, Clarissa; Armirotti, Andrea; Pötzsch, Alexandra; Walker, Tara L.; Fabel, Klaus; Nicassio, Francesco; Kempermann, Gerd; Tonelli, Davide De Pietri

doi:10.1016/j.stemcr.2019.04.020

Cited by 39 publications

(33 citation statements)

References 71 publications

(94 reference statements)

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“…28,35,36 Whether the manipulation of miRNAs during the chronic phase regulates epileptogenesis remains unknown. miR-135a regulates synaptic transmission and adult neurogenesis in the central nervous system (CNS) 37,38 and plays important roles in nervous system diseases. 39 In TLE patients, miR-135a expression is upregulated.…”

Section: Mir-135amentioning

confidence: 99%

MicroRNAs and target genes in epileptogenesis

et al. 2020

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Epilepsy is a chronic brain dysfunction. Current antiepileptic medicines cannot prevent epileptogenesis. Increasing data have shown that microRNAs (miRNAs) are selectively altered within the epileptic hippocampi of experimental models and human tissues, and these alterations affect the genes that control epileptogenesis. Furthermore, manipulation of miRNAs in animal models can modify epileptogenesis. As a result, miRNAs have been proposed as promising targets for treating epilepsy. We searched PubMed using the terms "microRNAs/miRNAs AND epilepsy", "microRNAs/miRNAs AND epileptogenesis", and "microRNAs/miRNAs AND seizure". We selected the articles in which the relationship between miRNAs and target gene(s) was validated and manipulation of miRNAs in in vivo epilepsy models modified epileptogenesis during the chronic phase via gene regulation. A total of 13 miRNAs were found in the present review. Based on the current analysis of miRNAs and their target gene(s), each miRNA has limitations as a potential epilepsy target. Importantly, miR-211 or miR-128 transgenic mice displayed seizures. These findings highlight new developments for epileptogenesis prevention. Developing novel strategies to modify epileptogenesis will be effective in curing epilepsy patients. This article provides an overview of the clinical application of miRNAs as novel targets for epilepsy.

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Section: Mir-135amentioning

confidence: 99%

MicroRNAs and target genes in epileptogenesis

et al. 2020

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“…They include extrinsic factors: cytokines, growth factors, neurotransmitters, and morphogens. Intrinsic factors are also involved, and include transcription factors, epigenetic regulators, and non-coding RNAs such as microRNAs [59,60,61]. They have been covered extensively in previous reviews [56,58,62,63,64].…”

Section: Adult Neurogenesis Is Linked With a Metabolic Shiftmentioning

confidence: 99%

Omega-3 Docosahexaenoic Acid Is a Mediator of Fate-Decision of Adult Neural Stem Cells

Hachem

Lagarde

2019

IJMS

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The mammalian brain is enriched with lipids that serve as energy catalyzers or secondary messengers of essential signaling pathways. Docosahexaenoic acid (DHA) is an omega-3 fatty acid synthesized de novo at low levels in humans, an endogenous supply from its precursors, and is mainly incorporated from nutrition, an exogeneous supply. Decreased levels of DHA have been reported in the brains of patients with neurodegenerative diseases. Preventing this decrease or supplementing the brain with DHA has been considered as a therapy for the DHA brain deficiency that could be linked with neuronal death or neurodegeneration. The mammalian brain has, however, a mechanism of compensation for loss of neurons in the brain: neurogenesis, the birth of neurons from neural stem cells. In adulthood, neurogenesis is still present, although at a slower rate and with low efficiency, where most of the newly born neurons die. Neural stem/progenitor cells (NSPCs) have been shown to require lipids for proper metabolism for proliferation maintenance and neurogenesis induction. Recent studies have focused on the effects of these essential lipids on the neurobiology of NSPCs. This review aimed to introduce the possible use of DHA to impact NSPC fate-decision as a therapy for neurodegenerative diseases.

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“…We characterized the miRNA profiles of the EDs after 2 weeks of treadmill exercise and administered these EDs to neuronal cells to investigate the cellular mechanisms for the neurogenic effects of exercise. miRNAs are small non-coding RNA molecules (about 22 nucleotides) found in various tissues, and have biological functions in cancer, the cardiovascular system, adipogenesis, and neurogenesis, mostly via post-transcriptional regulation of gene expression 39,40 . The majority of miRNAs are located within the cell, but some miRNAs can be secreted from cells and circulate in fluids 39 .…”

Section: Discussionmentioning

confidence: 99%

Neural maturation enhanced by exercise-induced extracellular derivatives

Moon

Yoon

Lee

et al. 2020

Sci Rep

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Physical activity has profound effects on neuronal progenitor cell growth, differentiation, and integration, but the mechanism for these effects is still ambiguous. Using a mouse model, we investigated the effects of two weeks of treadmill running on the dynamics of the size distribution and miRNA profiles of serum extracellular derivatives (EDs) using particle-sizing analysis and small RNA sequencing. We found that an increased average diameter of EDs in the running group compared with the sedentary group (p < 0.05), and 16 miRNAs were significantly altered (p < 0.05) in the running group. Furthermore, functional annotation analysis of differentially expressed miRNA-predicted target genes showed that many of these target genes are involved in the PI3K-Akt pathway. Exerciseinduced serum EDs increased Neuro2A cell viability and Akt phosphorylation. We also found that expression levels of neuronal maturation markers such as Microtubule-Associated Protein 2 (MAP2ab) and Neuronal nuclei (NeuN) were increased (p < 0.05, respectively), and that inhibition of the PI3K-Akt pathway by LY294002 pre-treatment ameliorated their expression in Neuro2A cells. Finally, the administration of exercise-induced EDs for 3 days increased the Histone 3 phosphorylation and β-iii tubulin expression in Ink/Arf null neural stem cells and progenitors (NSPCs) under each proliferation and differentiation condition. These results suggest that exercise-induced circulating EDs may mediate neuronal maturation during exercise. Enhanced synaptic plasticity, neurogenesis and neuronal maturation by prolonged exercise mediate improved aspects of brain function, such as motor skills, cognition and mood 1,2. Neuronal maturation is a continuous developmental process that modifies shape, structure and functional adaptations, playing a pivotal role in the augmentation of the neuronal network 3. Evidence suggests that the neurotrophic signaling system, neurotransmitter system, inflammatory system and cerebral vascular system are involved in neuronal maturation-related brain function and behaviors 4-8. Different types of physical activity have been shown to influence neuronal activities such as neurogenesis and maturation in various regions of the brain 9-11. Aerobic exercise increases cerebral blood flow (CBF) and angiogenesis in the motor cortex, which is linked to neurogenesis in mice and humans 11,12. Running also plays a role in neuronal maturation in mice 13. However, the effects of resistance exercise on neurogenesis remain controversial. Miriam et al. found that resistance exercise does not affect adult hippocampal neurogenesis in rats, while Nagamatsu et al. found that resistance exercise improves cognitive and functional brain plasticity in the elderly 14,15. The underlying mechanism for the beneficial effects of physical activity on the brain is currently being investigated. Research has focused on factors such as IRISIN, APLN (Apelin), CTSB (Cathepsin B) and many interleukins that circulate during exercise 16-20. The exercise-mimetic effects of e...

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MiR-135a-5p Is Critical for Exercise-Induced Adult Neurogenesis

Cited by 39 publications

References 71 publications

MicroRNAs and target genes in epileptogenesis

MicroRNAs and target genes in epileptogenesis

Omega-3 Docosahexaenoic Acid Is a Mediator of Fate-Decision of Adult Neural Stem Cells

Neural maturation enhanced by exercise-induced extracellular derivatives

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