PMID- 36561887
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221224
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 25
IP  - 12
DP  - 2022 Dec 22
TI  - miR-146a and miR-200b alter cognition by targeting NMDA receptor subunits.
PG  - 105515
LID - 10.1016/j.isci.2022.105515 [doi]
LID - 105515
AB  - MicroRNAs fine-tune gene regulation and can be targeted for therapeutic purposes. 
      We investigated the physiological roles of miR-146a and miR-200b that are 
      differentially expressed in neurological disorders such as Alzheimer's disease 
      and schizophrenia, particularly in learning and memory mechanisms. Using 
      bioinformatics tools and luciferase assay, we show interaction of these miRNAs 
      with transcripts of N-methyl-D-aspartate receptor (NMDAR) subunits Grin2A and 
      Grin2B. Overexpression of these miRNAs in primary hippocampal neurons caused 
      downregulation of GluN2B and GluN2A proteins. Stereotactic injections of these 
      miRNAs into rat hippocampus caused cognitive deficits in multiple behavioral 
      tests with decreased protein levels of GluN1, GluN2A, GluN2B, AMPAR subunit 
      GluR1, and Neuregulin 1. In pharmacologically treated rat models [MK-801 treated 
      and methylazoxymethanol acetate (MAM) treated], we found upregulated levels of 
      these miRNAs, implying their involvement in downregulating NMDAR subunits in 
      these models. These results suggest the importance of miR-146a-5p and miR-200b-3p 
      in hippocampus-dependent learning and memory.
CI  - (c) 2022 The Authors.
FAU - Gunasekaran, Sowmya
AU  - Gunasekaran S
AD  - Molecular Neurobiology Division, Rajiv Gandhi Centre for Biotechnology (RGCB), 
      Thiruvananthapuram 695014, India.
AD  - Research Scholar, Manipal Academy of Higher Education, Manipal, 576 104, India.
FAU - Omkumar, Ramakrishnapillai Vyomakesannair
AU  - Omkumar RV
AD  - Molecular Neurobiology Division, Rajiv Gandhi Centre for Biotechnology (RGCB), 
      Thiruvananthapuram 695014, India.
LA  - eng
PT  - Journal Article
DEP - 20221105
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC9763852
OTO - NOTNLM
OT  - Biological sciences
OT  - Cell biology
OT  - Cognitive neuroscience
COIS- The authors declare no competing interests.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/24 06:01
PMCR- 2022/11/05
CRDT- 2022/12/23 02:38
PHST- 2022/02/16 00:00 [received]
PHST- 2022/09/05 00:00 [revised]
PHST- 2022/11/02 00:00 [accepted]
PHST- 2022/12/23 02:38 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/24 06:01 [medline]
PHST- 2022/11/05 00:00 [pmc-release]
AID - S2589-0042(22)01787-4 [pii]
AID - 105515 [pii]
AID - 10.1016/j.isci.2022.105515 [doi]
PST - epublish
SO  - iScience. 2022 Nov 5;25(12):105515. doi: 10.1016/j.isci.2022.105515. eCollection 
      2022 Dec 22.