Table 2.
Evidence for miRNA regulation of LTP-related genes.
| Function | miRNA | mRNA | miRNA:mRNA interaction | Further information | Reference |
|---|---|---|---|---|---|
| Pre-synaptic vesicle release | miR-485-5p | SV2A | Direct inhibition in vitro | MiR-485-5p decreased the number of vesicles released after depolarization | Cohen et al. (2011) |
| miR-34a-5p | SYN1, SYN2 | Inhibition in vitro | MiR-34a-5p down-regulated 20 min (Joilin et al., 2014) and 5 h after LTP induction (Ryan et al., 2012); not regulated 30 min or 2 h after LTP induction (Wibrand et al., 2012) | Agostini et al. (2011) | |
| miR-34a-5p | SYT1, STX-1A | Direct inhibition in vitro | Increased miR-34a-5p correlated with decreased SYT1 and STX-1A in human Alzheimer’s disease (AD) brain. MiR-34a-5p down-regulated 20 min (Joilin et al., 2014) and 5 h after LTP induction (Ryan et al., 2012); not regulated 30 min or 2 h after LTP induction (Wibrand et al., 2012) | Agostini et al. (2011) | |
| miR-25-3p miR-185-5p | SERCA2 | Decreased miR-25-3p and miR-185-5p correlated with increased SERCA2 in vivo | Decreased miR-25-3p and miR-185-5p linked to increased LTP in Schizophrenia mouse model | Earls et al. (2012) | |
| Glutamate receptor regulation | miR-34a-5p miR-326-3p miR-19a-3p miR-193a-3p | Arc | Direct inhibition in vitro | MiR-34a-5p, miR-326-3p, miR-19a-3p, miR-193a-3p not regulated 30 min or 2 h after LTP induction. MiR-34a-5p down-regulated 20 min (Joilin et al., 2014) and 5 h after LTP induction in vivo (Ryan et al., 2012); not regulated 30 min or 2 h after LTP induction (Wibrand et al., 2012) | Wibrand et al. (2012) |
| miR-181a-5p | GluA2 | Direct inhibition in vitro (minimal) | MiR-181a-5p reduced spine volume and density in hippocampal neurons | Edbauer et al. (2010), Saba et al. (2012) | |
| miR-138-5p | GluA2 | Inhibition in vitro | MiR-138-5p reduced spine volume in hippocampal neurons (APT-1 dependent) | Siegel et al. (2009) | |
| miR-485-5p | GluA2 | Inhibition in vitro | MiR-485-5p reduced spine density and increased immature spines in hippocampal neurons | Cohen et al. (2011) | |
| miR-124-3p | GluA2 | Direct inhibition in vitro (minimal) | – | Edbauer et al. (2010) | |
| miR-132-3p | GluA1, GluN2A, GluN2B | Indirect up-regulation in vitro | MiR-132-3p up-regulated 2 h after LTP induction (Wibrand et al., 2010, 2012); miR-132-3p down-regulated 20 min after LTP induction (Joilin et al., 2014) | Kawashima et al. (2010) | |
| miR-219a-5p | GluA1 | Direct inhibition of CaMKIIy in vivo, which regulates GluA1 | MiR-219a-5p down-regulated 2 h after LTP induction (Wibrand et al., 2010) | Kocerha et al. (2009) | |
| miR-125b-5p | GluN2A | Direct inhibition in vitro | MiR-125b-5p reduced spine width and increased length in hippocampal neurons (FMRP- dependent) | Edbauer et al. (2010) | |
| miR-212-3p | BDNF | Indirect inhibition via MeCP2 in vivo | – | Im et al. (2010) | |
| miR-132-3p | BDNF | miR-132-3p indirectly inhibits BDNF via MeCP2; BDNF indirectly up-regulates miR-132-3p via TrkB and ERK1/2 | MiR-132-3p up-regulated 2 h after LTP induction (Wibrand et al., 2010, 2012); miR-132-3p down-regulated 20 min after LTP induction (Joilin et al., 2014) | Klein et al. (2007), Kawashima et al. (2010) | |
| miR-206-3p | BDNF | Direct inhibition in vivo | MiR-206-3p up-regulated in Tg2576 AD mice and human AD brain samples. Intraventricular injection of miR-206-3p antagomir increased BDNF and improved memory | Lee et al. (2012b) | |
| Transcription | miR-132-3p | MeCP2 | Reciprocal inhibition: MeCP2 inhibits miR-132-3p in vitro; miR-132-3p inhibits MeCP2 in vivo; MeCP2 KO decreased miR-132-3p in vivo | MiR-132-3p up-regulated 2 h after LTP induction (Wibrand et al., 2010, 2012); miR-132-3p down-regulated 20 min after LTP induction (Joilin et al., 2014) | Klein et al. (2007), Hansen et al. (2010), Im et al. (2010), Tognini et al. (2011) |
| miR-212-3p | MeCP2 | Reciprocal inhibition: MeCP2 inhibits miR-132 in vitro; miR-212-3p inhibits MeCP2 in vivo | MiR-212-3p up-regulated 2 h after LTP induction (Wibrand et al., 2010) | Im et al. (2010) | |
| miR-34c-5p | SIRT1 | Direct inhibition in vivo | Increased miR-34c-5p correlated with decreased SIRT1 in memory impairment mouse models (APPS1-21 and aged) | Zovoilis et al. (2011) | |
| miR-124-3p | CREB, EGR1 | Direct inhibition in vitro | – | Rajasethupathy et al. (2009), Yang et al. (2012) | |
| miR-134-5p | CREB | Direct inhibition in vitro | – | Gao et al. (2010) | |
| Activity-dependent dendritogenesis | miR-134-5p | Pum2 | Direct inhibition in vitro | Interaction only occurs after neuronal activity, not under basal conditions; miR-134-5p buffers Pum2 in a narrow range that is critical for activity-dependent dendritogenesis. MiR-134-5p decreased spine volume in hippocampal neurons | Schratt et al. (2006), Fiore et al. (2009) |
| miR-134-5p | Limk1 | Direct inhibition in vitro | Inhibition of Limk1 in dendrites relieved by BDNF | Schratt et al. (2006) | |
| miR-132-3p | p250GAP | Direct inhibition in vitro and in vivo | p250GAP regulates existing spine growth via Rac1 and kalirin-7; miR-132-3p affects spine size in vivo. MiR-132-3p up-regulated 2 h after LTP induction (Wibrand et al., 2010, 2012); miR-132-3p down-regulated 20 min after LTP induction (Joilin et al., 2014) | Impey et al. (2010), Mellios et al. (2011) | |
| miR-138-5p | APT1 | Direct inhibition in vitro | MiR-138-5p and APT1 co-localized at the synapse; miR-138-5p reduced spine volume in hippocampal neurons (APT-1 dependent) | Banerjee et al. (2009), Siegel et al. (2009) | |
| miR-19b-3p | PTEN | Inhibition in vitro | MiR-19b-3p up-regulated after fear conditioning; miR-19b-3p increased total neurite length in hippocampal neurons | Kye et al. (2011) | |
| miR-188-5p | Nrp2 | Direct inhibition in vitro | MiR-188-5p has no effect on dendritogenesis in hippocampal neurons MiR-188-5p is up-regulated 1 h after LTP induction (Lee et al., 2012a) | Lee et al. (2012a) |
AD, Alzheimer’s disease; APT1, acyl-protein thioesterase 1; ARC, activity-related cytoskeleton-associated protein; BDNF, brain-derived neurotrophic factor; CaMKIIγ, calcium/calmodulin-dependent protein kinase II gamma; CREB, cAMP response element-binding protein; EGR1, early growth response 1; GluA1, glutamate receptor, ionotropic, AMPA 1; GluA2, glutamate receptor, ionotropic, AMPA 2; GluN2A, glutamate receptor, ionotropic, NMDA 2A; GluN2B, glutamate receptor, ionotropic, NMDA 2B; LIMK1, LIM domain kinase 1; LTP, long-term potentiation; MECP2, methyl CpG binding protein 2; NRP2, neurophilin 2; PTEN, phosphatase and tensin homolog; PUM2, pumilio homolog 2; SERCA2, sarco/endoplasmic reticulum Ca2+ ATPase; SIRT1, sirtuin 1; STX1A, syntaxin 1a; SV2A, synaptic vesicle glycoprotein 2A; SYN1, synapsin I; SYN2, synapsin II; SYT1, synaptotagmin I.