Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Role of LncMALAT1-miR-141-3p/200a-3p-NRXN1 Axis in the Impairment of Learning and Memory Capacity in ADHD

Y. Mu, J. Li, S. Zhang, F. Zhong, X. Zhang, J. Song, H. Yuan, T. Tian, Y. Hu

. 2023 ; 72 (5) : 645-656. [pub] 2023Nov28

Jazyk angličtina Země Česko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc23020556

As a prevalent neurodevelopmental disease, attention-deficit hyperactivity disorder (ADHD) impairs the learning and memory capacity, and so far, there has been no available treatment option for long-term efficacy. Alterations in gene regulation and synapse-related proteins influence learning and memory capacity; nevertheless, the regulatory mechanism of synapse-related protein synthesis is still unclear in ADHD. LncRNAs have been found participating in regulating genes in multiple disorders. For instance, lncRNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has an essential regulatory function in numerous psychiatric diseases. However, how MALAT1 influences synapse-related protein synthesis in ADHD remains largely unknown. Here, our study found that MALAT1 decreased in the hippocampus tissue of spontaneously hypertensive rats (SHRs) compared to the standard controls, Wistar Kyoto (WKY) rats. Subsequent experiments revealed that MALAT1 enhanced the expression of neurexin 1 (NRXN1), which promoted the synapse-related genes (SYN1, PSD95, and GAP43) expression. Then, the bioinformatic analyses predicted that miR-141-3p and miR-200a-3p, microRNAs belonging to miR-200 family and sharing same seed sequence, could interact with MALAT1 and NRXN1 mRNA, which were further confirmed by luciferase report assays. Finally, rescue experiments indicated that MALAT1 influenced the expression of NRXN1 by sponging miR-141-3p/200a-3p. All data verified our hypothesis that MALAT1 regulated synapse-related proteins (SYN1, PSD95, and GAP43) through the MALAT1-miR-141-3p/200a-3p-NRXN1 axis in ADHD. Our research underscored a novel role of MALAT1 in the pathogenesis of impaired learning and memory capacity in ADHD and may shed more light on developing diagnostic biomarkers and more effective therapeutic interventions for individuals with ADHD.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc23020556
003      
CZ-PrNML
005      
20250502124336.0
007      
ta
008      
231215s2023 xr f 000 0|eng||
009      
AR
024    7_
$a 10.33549/physiolres.935011 $2 doi
035    __
$a (PubMed)38015763
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xr
100    1_
$a Mu, Y. $u The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China; Department of Children's Health Care, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Maternal and Child Health Care Hospital, Nanjing, Jiangsu, China. 972677371@qq.com, 13182823903@126.com
245    10
$a Role of LncMALAT1-miR-141-3p/200a-3p-NRXN1 Axis in the Impairment of Learning and Memory Capacity in ADHD / $c Y. Mu, J. Li, S. Zhang, F. Zhong, X. Zhang, J. Song, H. Yuan, T. Tian, Y. Hu
520    9_
$a As a prevalent neurodevelopmental disease, attention-deficit hyperactivity disorder (ADHD) impairs the learning and memory capacity, and so far, there has been no available treatment option for long-term efficacy. Alterations in gene regulation and synapse-related proteins influence learning and memory capacity; nevertheless, the regulatory mechanism of synapse-related protein synthesis is still unclear in ADHD. LncRNAs have been found participating in regulating genes in multiple disorders. For instance, lncRNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has an essential regulatory function in numerous psychiatric diseases. However, how MALAT1 influences synapse-related protein synthesis in ADHD remains largely unknown. Here, our study found that MALAT1 decreased in the hippocampus tissue of spontaneously hypertensive rats (SHRs) compared to the standard controls, Wistar Kyoto (WKY) rats. Subsequent experiments revealed that MALAT1 enhanced the expression of neurexin 1 (NRXN1), which promoted the synapse-related genes (SYN1, PSD95, and GAP43) expression. Then, the bioinformatic analyses predicted that miR-141-3p and miR-200a-3p, microRNAs belonging to miR-200 family and sharing same seed sequence, could interact with MALAT1 and NRXN1 mRNA, which were further confirmed by luciferase report assays. Finally, rescue experiments indicated that MALAT1 influenced the expression of NRXN1 by sponging miR-141-3p/200a-3p. All data verified our hypothesis that MALAT1 regulated synapse-related proteins (SYN1, PSD95, and GAP43) through the MALAT1-miR-141-3p/200a-3p-NRXN1 axis in ADHD. Our research underscored a novel role of MALAT1 in the pathogenesis of impaired learning and memory capacity in ADHD and may shed more light on developing diagnostic biomarkers and more effective therapeutic interventions for individuals with ADHD.
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a zvířata $7 D000818
650    12
$a hyperkinetická porucha $x genetika $7 D001289
650    12
$a RNA dlouhá nekódující $x genetika $x metabolismus $7 D062085
650    _2
$a potkani inbrední WKY $7 D011921
650    12
$a mikro RNA $x genetika $x metabolismus $7 D035683
650    _2
$a regulace genové exprese $7 D005786
655    _2
$a časopisecké články $7 D016428
700    1_
$a Li, J.
700    1_
$a Zhang, S.
700    1_
$a Zhong, F.
700    1_
$a Zhang, X..
700    1_
$a Song, J.
700    1_
$a Yuan, H.
700    1_
$a Tian, T.
700    1_
$a Hu, Y.
773    0_
$w MED00003824 $t Physiological research $x 1802-9973 $g Roč. 72, č. 5 (2023), s. 645-656
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38015763 $y Pubmed
910    __
$a ABA008 $b A 4120 $c 266 $y p $z 0
990    __
$a 20231215 $b ABA008
991    __
$a 20250502124328 $b ABA008
999    __
$a ok $b bmc $g 2255288 $s 1206995
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2023 $b 72 $c 5 $d 645-656 $e 2023Nov28 $i 1802-9973 $m Physiological research $n Physiol Res $x MED00003824
LZP    __
$b NLK116 $a Pubmed-20231215

Najít záznam

Citační ukazatele

Možnosti archivace