Dataset Information

Mir125b-2 imprinted in human but not mouse brain regulates hippocampal function and circuit in mice.

ABSTRACT: 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.

SUBMITTER: Chou MY

PROVIDER: S-EPMC10014956 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mir125b-2 imprinted in human but not mouse brain regulates hippocampal function and circuit in mice.

Chou Ming-Yi MY Cao Xuhui X Hou Kuan-Chu KC Tsai Meng-Han MH Lee Chih-Yu CY Kuo Meng-Fai MF Wu Vin-Cent VC Huang Hsin-Yi HY Akbarian Schahram S Chang Sheng-Kai SK Hu Chung-Yi CY Lin Shu-Wha SW Huang Hsien-Sung HS

Communications biology 20230314 1

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-2m-/p- mice showed impaired learning and memory, and anxiety, whose functions were hippocampus-dependent. Hippocampal granule cells from Mir125b-2m ...[more]

PMID: 36918719

Similar Datasets

Project description:Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation and downregulated in the aged brain. In addition to revitalizing other aged tissues, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high translational value for targeting ageing- or disease-associated hippocampal dysfunction.

Dataset Information

Mir125b-2 imprinted in human but not mouse brain regulates hippocampal function and circuit in mice.

Publications

Mir125b-2 imprinted in human but not mouse brain regulates hippocampal function and circuit in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets