MicroRNA-219 decreases hippocampal long-term potentiation inhibition and hippocampal neuronal cell apoptosis in type 2 diabetes mellitus mice by suppressing the NMDAR signaling pathway
Authors: Jun-Jie Dong
Zheng-Wen Chen
Shu-Fen Yang
Muyasi Shaer
Ling Zhang
Ying Wang
Beili Jiapaer
Journal: CNS neuroscience & therapeutics (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MicroRNA-219; NMDAR signaling pathway; apoptosis; hippocampal neuronal cells; long-term potentiation
Affiliations: Department of Cadre Health Care, the Xinjiang Uygur Autonomous Region People's Hospital, Urumchi, China., Department of Anesthesiology, the Second Affiliated Hospital of Xinjiang Medical University, Urumchi, China., Department of Nephrology, the Xinjiang Uygur Autonomous Region People's Hospital, Urumchi, China.

Abstract:  Objective: Type 2 diabetes mellitus (T2DM) is a complex polygenic disease that causes hyperglycemia and accounts for 90%-95% of all diabetes mellitus cases. Hence, this study aimed to examine the effects of microRNA-219 (miR-219) on inhibition of long-term potentiation (LTP) and apoptosis of hippocampal neuronal cells in T2DM mice through the N-methyl-d-aspartate receptor (NMDAR) signaling pathway regulation. Methods: The T2DM mouse models were established, after which LTP in vivo was recorded by means of electrical biology, and the fasting blood glucose of mice was measured. Next, the density of pyramidal neurons in each group was calculated. Additionally, the expression levels of miR-219, the NMDAR signaling pathway [NMDAR1 (NR) 1, NR2A, and NR2B), downstream target proteins [calmodulin-dependent protein kinase-II (CaMK-II) and cAMP response element binding protein (CREB)], and apoptosis-related factors [Bcl2-associated X protein (Bax), c-caspase-9 and c-caspase-3] in the hippocampal tissues were determined. Finally, immunohistochemistry was applied to detect and measure the positive expression of Bax, caspase-9, and caspase-3 proteins. Results: The results showed that upregulation of miR-219 increases LTP and density of pyramidal neurons in the hippocampal tissues of mice, while it decreases blood glucose of db/db mice. In addition, miR-219 upregulation also leads to decreased mRNA levels of NR1, NR2A, NR2B, CaMK-II, and CREB and protein levels of NR1, NR2A, NR2B, CaMK-II, CREB, p-CREB, Bax, c-caspase-9, and c-caspase-3. Furthermore, upregulation of miR-219 inhibits positive expression of Bax, caspase-9, and caspase-3 proteins, leading to the suppression of hippocampal neuronal cell apoptosis. Conclusion: The findings from this study indicated that the upregulation of miR-219 decreases LTP inhibition and hippocampal neuronal cell apoptosis in T2DM mice by downregulating the NMDAR signaling pathway, therefore suggesting that MiR-219 might be a future therapeutic strategy for T2DM. 

Retracted: No

PubPeer comments:
 Figure 3. * Blue boxes: The miR-219 mimic and APV panels appear to overlap, if one of the panels is rotated 180 degrees. ![file] , 
 Figure 6. * Some panels appear to show overlapping areas with each other (rectangular boxes of the same color), and some areas appear to be visible multiple times within the same panel or across panels (rounded boxes of the same color). ![file] , 
 Figure 5. The Western blots in Figure 5A of this paper appear to look very similar to the  Sewing-machine bands as described in a recent post by Smut Clyde on Leonid Schneider s blog: https: forbetterscience.com 2020 09 14 dead-horses-wont-flog-themselves Here is a screenshot of Figure 5A s panels: ![file] , 
 #2 ![file] One panel at right centre, marked with a black rectangle, overlaps with a panel of Fig 5A from [Jin et al (2017)] . ![file] , 
 #1 Fig 3A again. ![file] Brown and light green rectangles mark overlaps with Fig 3 from [Piao et al (2018)] [retracted]... ![file] And Fig 2 from [Zhou et al (2018)] . ![] And Fig 3 of [Han et al (2018)] , marked there in black. ![] , 
 Fig 6 again. ![] Panel also features in Fig 10A of [Zhang et al (2018)] . ![] , 
 Retracted [30 July 2021] . -------------------------------------------- The above article, first published online on May 27, 2018, in Wiley Online Library , has been retracted as requested by the journal s editorial team and with the agreement of John Wiley Sons Ltd. The retraction has been agreed following a formal investigation into the allegation of potential scientific misconduct, which revealed that several image elements of the experimental data were published elsewhere in a different scientific context or repeatedly used within the images. Thus, the editors consider the conclusions of this article to be invalid.u202fThe authors were not available to comment on these inconsistencies despite of multiple inquires by the journal. ,