Table 1.
Examples of miRNAs probably involved in learning/memory processes. References indicating their presence in extracellular vesicles are given in the last column.
| miRNA [Refs] | Targets [Refs] | Primary Functions [Refs] | Presence in Exosomes/MVs [Refs] |
|---|---|---|---|
| miR-9-derived miR-9-3p [226] | Dystrophin [226]; Voltage-dependent Calcium channel, g subunit [226,227]; Leucine rich repeat transmembrane neuronal 1 [226,228]; Cadherin 2 [226,229]; Fibronectin [230]; Calcineurin B, type I [226,231] |
Regulates synaptic plasticity and memory [226] | Found in serum exosomes of acute ischemic stroke patients [217] |
|
miR-17-92 cluster: miR-17, miR-18a, miR-19a, miR-19b, miR-20a, and miR-92a [213,232,233,234] |
Phosphatase and Tensin Homolog (PTEN) [211,234] | -Regulate axonal outgrowth in development [211]; -Regulate adult hippocampal neurogenesis, anxiety, and depression [232]; -Enhance neuroplasticity and functional recovery after stroke [233,234]; -Enhance neurite remodeling, neurogenesis and angiogenesis in post-stroke rats [233]; -Ablation in mouse impairs hippocampal-dependent learning and memory [212] |
miR-19a found in exosomes [213,233] |
| miR-26a [209] | PTEN, GSK-3, BDNF [209] | Stimulates neurite/axonal elongation [209] | Found in astrocytic exosomes [209] |
| miR-29c [235] | Beta secretase 1 (BACE1) [236] | This microRNA can be an endogenous regulator of the BACE 1 enzyme, and thus of beta amyloid precursor protein (APP) metabolism. [236] | Found in exosomes contained in frozen post-mortem prefrontal cortex from bipolar individuals [235] |
| miR-34a [237] | Activity-regulated cytoskeleton-associated protein (Arc) Chicken ovalbumin upstream promoter transcription factor-interacting proteins 2 (Ctip2) Transcription factor 4 (TCF4) Ubiquitin-conjugating enzyme E2 G1 (Ube2g1) [237] |
Regulates Synaptic Efficacy in the Adult Dentate Gyrus In Vivo [237]; Overexpressed in Alzheimer’s Disease (AD) patients [238] |
Found in exosomes of overexpressing primary neurons in culture [238] |
| miR-124 [239] | Targets, EZH2 [216] and the glucocorticoid receptor [240] |
Regulate early memory phases [239]; miR-124 plays also a role in depression [240]; miR-124 regulates cell fate (prevents astrocytes from expressing neuronal proteins) [216] |
miR-124 found in serum exosomes of acute ischemic stroke patients [217] |
| miR-125b [241,242] | Nestin [241] | Regulates differentiation and migration in neural stem/progenitor cells [241] | Found in exosomes from adult astrocytes [243] |
| miR-132 [244] | Eukaryotic elongation factor 2 kinase (eef2k) [244] | Regulates maintenance of brain vascular integrity [244] | Found in neuronal exosomes delivered to BCECs [244] |
| miR-134 [245] | Caspase-8 [245] | -Regulates survival of oligodendrocytes [245]; -Regulates the size of dendritic spines, excitatory synaptic transmission, and synaptic plasticity [246] |
Found in bone marrow-derived mesenchymal stem cells (BMSCs) Exosomes [245] |
| miR-139 [247] | Cannabinoid receptor type 2 (CB2) [247] | Regulates hippocampal function, and affects learning and memory acquisition [247] | miR-139-derived miR-139-5p Found in exosomes of AD patients [248] |
| miR-497 [235] | B-cell lymphoma 2 (Bcl-2)/Bcl-w genes [249] | Regulates ischemic neuronal death in N2A neuroblastoma cells and also in a mouse model of middle cerebral artery occlusion (MCAO) [249] | Found in exosomes contained in frozen post-mortem prefrontal cortex from schizophrenia patients [235] |