Synapse is the physiological site or junction between Presynaptic and postsynaptic neurons that helps transmit electrical impulses and chemical neurotransmitters are released from the presynaptic neurons to propagate the signal to postsynaptic neurons. Several pieces of evidence support the presence of miRNA in the synaptic terminal area (locally) that modulates gene expression and regulates protein synthesis through post-transcriptional modifications. Therefore, eventually promotes the development of synapses or neural networks, improving synaptic activity, and synaptic plasticity.
Micro RNA, often known as miRNA is an important non-coding RNA that plays a pivotal role in epigenetic regulations of gene expression. The transcriptional genes of miRNA are synthesized generally by RNA Polymerase II into primary miRNA (pri-miRNA) followed by cleavage into precursor miRNA (pre-miRNA) by nuclear enzyme Drosha. Subsequently, it is cleaved by Dicer into miRNA and miRNA* and RNA Induced silencing complex (RISC) degrades miRNA* and attaches to another miRNA, to form mature miRNA.
Due to the long distance between the soma and the synaptic terminal (e.g., axon terminal, dendrites, dendritic spines, etc.), neurons synthesize their synapse activity-associated proteins locally, close to the synapse, and miRNA plays a crucial role in regulating the synthesis of those proteins.
Moreover, it is also reported that these indicative miRNAs are region-specific (I. e., different miRNA's presence in different regions of the brain). However, research is underway to better comprehend the underlying mechanism that determines whether pre-miRNA originating from the neuronal cell body or locally present at the synapse causes miRNA to become mature.
Some studies suggested that Ca2+ signaling associated with NMDA receptors impacts the Dicer, which affects the learning and memory process. Furthermore, NMDA and AMPA receptors are influenced by miRNA activity in several other ways. Some of these miRNAs are miR 129, miR 501 3p, miR 146a 5p, miR 384 5p, miR 223, miR 212, miR 188, miR 125b, miR 132, miR 26a, miR 137, etc. which either induces or inhibits the protein translation process (including signaling and structural proteins both in pre-and postsynaptic neurons) and control the synaptic transmission and synaptic plasticity.
Moreover, it's also been discovered that miR182 contributes to the regulation of fear memory. It has been demonstrated that Dicer1 inactivation eventually increases dendritic spine length and promotes neural excitability in the excitatory neurons located in the hippocampus. On the other hand, lowering RISC activity results in a decrease in the dendritic spine density and amplitude of miniature excitatory postsynaptic current or mEPSC.
Current data has shown some information about miRNA activity in modifications of dendritic spine morphology which consequently affects the long-term potentiation (LTP), long-term facilitation (LTF), and long-term depression (LTD) formation. Mir 124, miR 134, miR 132, miR 185, miR 181, miR 29a/b, miR 22, miR 125, miR 138, etc. are some well-identified miRNAs with relative functions. According to recent findings, the function of miRNA is significantly specific to the brain over other organs. Although a small portion of this concept has been experimentally validated, much more has to be understood about the underlying mechanisms in order to facilitate the use of miRNA as a biomarker to treat an array of neurological disorders, including neurodegenerative diseases.
Reference:
Hu, Z., & Li, Z. (2017). miRNAs in synapse development and synaptic plasticity. Current
opinion in neurobiology, 45, 24–31. https://doi.org/10.1016/j.conb.2017.02.014
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