Journal
COMMUNICATIONS BIOLOGY
Volume 6, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-023-04655-y
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Knockout of Mir125b-2 in mice leads to defects in hippocampus-related behaviors and affects hippocampal expression of Grin2a and NMDAR-mediated currents. Paternal expression of MIR125B2 is observed in the human brain. Mir125b-2 knockout mice show impaired learning, memory, and anxiety, and altered excitability and synaptic transmission in hippocampal granule cells. This study reveals the functional mechanisms of a species-specific imprinted microRNA in the brain.
Knockout of Mir125b-2 in mice leads to defects in hippocampus-related behaviors and affects hippocampal expression of Grin2a and NMDAR-mediated currents. Genomic imprinting predominantly occurs in the placenta and brain. Few imprinted microRNAs have been identified in the brain, and their functional roles in the brain are not clear. Here we show paternal, but not maternal, expression of MIR125B2 in human but not mouse brain. Moreover, Mir125b-2(m)(-)(/p)(-) mice showed impaired learning and memory, and anxiety, whose functions were hippocampus-dependent. Hippocampal granule cells from Mir125b-2(m)(-)(/p)(-) mice displayed increased neuronal excitability, increased excitatory synaptic transmission, and decreased inhibitory synaptic transmission. Glutamate ionotropic receptor NMDA type subunit 2A (Grin2a), a key regulator of synaptic plasticity, was physically bound by miR-125b-2 and upregulated in the hippocampus of Mir125b-2(m)(-)(/p)(-) mice. Taken together, our findings demonstrate MIR125B2 imprinted in human but not mouse brain, mediated learning, memory, and anxiety, regulated excitability and synaptic transmission in hippocampal granule cells, and affected hippocampal expression of Grin2a. Our work provides functional mechanisms of a species-specific imprinted microRNA in the brain.
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