PMID- 37321367
OWN - NLM
STAT- Publisher
LR  - 20230814
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 526
DP  - 2023 Aug 21
TI  - miR-146a-5p Modulates Adult Hippocampal Neurogenesis Deficits Through 
      Klf4/p-Stat3 Signaling in APP/PS1 Mice.
PG  - 314-325
LID - S0306-4522(23)00260-9 [pii]
LID - 10.1016/j.neuroscience.2023.06.004 [doi]
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease, and 
      currently, no effective treatment strategies exist for this condition. MicroRNAs 
      (miRNAs) have emerged as promising therapeutic targets of AD. Previous studies 
      have highlighted the significant role of miR-146a-5p in regulating adult 
      hippocampal neurogenesis (AHN). Here, we aimed to investigate whether miR-146a-5p 
      plays a role in the mechanisms of AD. We employed quantitative real-time PCR 
      (qRT-PCR) to assess the expression of miR-146a-5p. Additionally, we examined the 
      expression of Kruppel-like factor 4 (Klf4), Signal transducer and activator of 
      transcription 3 (Stat3), and phosphorylated Stat3 (p-Stat3) using western blot 
      analysis. Furthermore, we validated the interaction between miR-146a-5p and Klf4 
      using a dual-luciferase reporter assay. Immunofluorescence staining was employed 
      to evaluate AHN. And Contextual fear conditioning discrimination learning 
      (CFC-DL) experiment was used to detect pattern separation. Our findings in the 
      hippocampus of APP/PS1 mice revealed upregulated levels of miR-146a-5p and 
      p-Stat3, while Klf4 levels were downregulated. Interestingly, both miR-146a-5p 
      antagomir and p-Stat3 inhibitor obviously rescued neurogenesis and pattern 
      separation in APP/PS1 mice. Moreover, application of miR-146a-5p agomir reversed 
      the protective effects of Klf4 upregulation. These findings open new avenues for 
      protection against AD through the modulation of neurogenesis and cognitive 
      decline via the miR-146a-5p/Klf4/p-Stat3 pathway.
CI  - Copyright (c) 2023. Published by Elsevier Ltd.
FAU - Deng, Li-Jun
AU  - Deng LJ
AD  - Department of Neurosurgery, The Affiliated Hospital of Jianghan University, Wuhan 
      430022, PR China.
FAU - Wu, Dan
AU  - Wu D
AD  - Department of Neurosurgery, The Affiliated Hospital of Jianghan University, Wuhan 
      430022, PR China.
FAU - Yang, Xiao-Fan
AU  - Yang XF
AD  - Department of Hand Surgery, Wuhan Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, PR China.
FAU - Li, Tao
AU  - Li T
AD  - Department of Hand Surgery, Wuhan Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, PR China. Electronic 
      address: tli2007@hust.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230613
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
SB  - IM
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Klf4
OT  - miR-146a-5p
OT  - neurogenesis
OT  - p-Stat3
EDAT- 2023/06/16 01:08
MHDA- 2023/06/16 01:08
CRDT- 2023/06/15 19:14
PHST- 2022/11/08 00:00 [received]
PHST- 2023/06/05 00:00 [revised]
PHST- 2023/06/07 00:00 [accepted]
PHST- 2023/06/16 01:08 [pubmed]
PHST- 2023/06/16 01:08 [medline]
PHST- 2023/06/15 19:14 [entrez]
AID - S0306-4522(23)00260-9 [pii]
AID - 10.1016/j.neuroscience.2023.06.004 [doi]
PST - ppublish
SO  - Neuroscience. 2023 Aug 21;526:314-325. doi: 10.1016/j.neuroscience.2023.06.004. 
      Epub 2023 Jun 13.