2. Academic Validation
  3. Quercetin modulates expression of serum exosomal long noncoding RNA NEAT1 to regulate the miR-129-5p/BDNF axis and attenuate cognitive impairment in diabetic mice

Quercetin modulates expression of serum exosomal long noncoding RNA NEAT1 to regulate the miR-129-5p/BDNF axis and attenuate cognitive impairment in diabetic mice

  • Life Sci. 2024 Jan 20:122449. doi: 10.1016/j.lfs.2024.122449.
Hui Wang 1,  Narayanan Jayasankar 2,  Tamilanban Thamaraikani 2,  Patrik Viktor 3,  Mohamed Mohany 4,  Salim S Al-Rejaie 4,  Hasan Khalid Alammar 5,  Enaam Anad 6,  Farah Alhili 7,  Sinan F Hussein 8,  Ali H Amin 9,  Natrayan Lakshmaiya 10,  Muhammad Ahsan 11,  Abolfazl Bahrami 12,  Reza Akhavan-Sigari 13
Affiliations

Affiliations

  • 1 The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu 322000, China.
  • 2 Department of Pharmacology, SRM Institute of Science and Technology, SRM College of Pharmacy, Kattankulathur 603203, Tamil Nadu, India.
  • 3 Keleti Károly Faculty of Business and Management, Óbuda University, Tavaszmező, H-1084 Budapest, Hungary.
  • 4 Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • 5 College of Dentistry, Al-Mustaqbal University, 51001 Babylon, Iraq.
  • 6 Department of Medical Laboratory Technics, Al-Noor University College, Nineveh, Iraq.
  • 7 Medical Technical College, Al-Farahidi University, Iraq.
  • 8 Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq.
  • 9 Zoology Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt.
  • 10 Department of Mechanical Engineering, Saveetha School of Engineering, SIMATS, Chennai, Tamil Nadu, India.
  • 11 Department of Measurements and Control Systems, Silesian University of Technology, Gliwice, Poland; Joint Doctoral School, Silesian University of Technology, Akademicka 2A, Gliwice, Poland. Electronic address: [email protected].
  • 12 Biomedical Center for Systems Biology Science Munich, Ludwig-Maximilians-University, Munich, Germany. Electronic address: [email protected].
  • 13 Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw, Poland; Department of Neurosurgery, University Medical Center Tuebingen, Germany.
PMID: 38253310 DOI: 10.1016/j.lfs.2024.122449
Abstract

Aims: Cognitive impairment poses a considerable health challenge in the context of type 2 diabetes mellitus (T2DM), emphasizing the need for effective interventions. This study delves into the therapeutic efficacy of quercetin, a natural flavonoid, in mitigating cognitive impairment induced by T2DM in murine models.

Materials and methods: Serum exosome samples were obtained from both T2DM-related and healthy mice for transcriptome sequencing, enabling the identification of differentially expressed mRNAs and long noncoding RNAs (lncRNAs). Subsequent experiments were conducted to ascertain the binding affinity between mmu-miR-129-5p, NEAT1 and BDNF. The structural characteristics and dimensions of isolated exosomes were scrutinized, and the expression levels of exosome-associated proteins were quantified. Primary mouse hippocampal neurons were cultured for in vitro validation, assessing the expression of pertinent genes as well as neuronal vitality, proliferation, and Apoptosis capabilities. For in vivo validation, a T2DM mouse model was established, and quercetin treatment was administered. Changes in various parameters, cognitive ability, and the expression of insulin-related proteins, along with pivotal signaling pathways, were monitored.

Key findings: Analysis of serum exosomes from T2DM mice revealed dysregulation of NEAT1, mmu-miR-129-5p, and BDNF. In vitro investigations demonstrated that NEAT1 upregulated BDNF expression by inhibiting mmu-miR-129-5p. Overexpression of mmu-miR-129-5p or silencing NEAT1 resulted in the downregulation of insulin-related protein expression, enhanced Apoptosis, and suppressed neuronal proliferation. In vivo studies validated that quercetin treatment significantly ameliorated T2DM-related cognitive impairment in mice.

Significance: These findings suggest that quercetin holds promise in inhibiting hippocampal neuron Apoptosis and improving T2DM-related cognitive impairment by modulating the NEAT1/miR-129-5p/BDNF pathway within serum exosomes.

Keywords

BDNF; Hippocampal neurons; NEAT1; Quercetin; Serum exosomes; Type 2 diabetes; miR-129-5p.

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