MiR-221 is involved in depression by regulating Wnt2/CREB/BDNF axis in hippocampal neurons

Abstract

Objective: The aim of this study was to investigate the mechanism of miR-221 in depression. Methods: The molecules expressions were measured by qRT-PCR and western blot. The sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST) were used to detect depressive-like symptoms. MTT assay and flow cytometric was used to measure the proliferation and apoptosis of hippocampal neuronal. Results: MiR-221 expression in the cerebrospinal fluid and serum of major depressive disorder patients and the hippocampus of chronic unpredictable mild stress (CUMS) mice were increased, while the expression of Wnt2, p-CREB and BDNF were decreased. Additionally, silence of miR-221 increased sucrose preference of CUMS mice and shortened the immobility time of CUMS mice in SPT and FST. MiR-221 could targeted regulate Wnt2, and knockdown of Wnt2 reversed the effect of miR-221 inhibitor on the proliferation and apoptosis of hippocampal neurons and countered the promoting effect of miR-221 inhibitor on the expression of Wnt2, p-CREB and BDNF. Conclusion: MiR-221 could promote the development of depression by regulating Wnt2/CREB/ BDNF axis. ARTICLE HISTORY

Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice

“…CREB is a transcription factor, and its interaction with BDNF has a critical role in the altered neuroplasticity observed in major depression. Consistently, our previous iTRAQ-based proteomics analysis reported a disruption of the CAMKII-CREB-BDNF signaling pathway in gut microbiome remodeling mice 60 , and p-CREB was decreased in the hippocampus of chronic unpredictable mild stress exposed mice 61 . In addition, increased p-CREB is related to treatment response in MDD patients 62 .…”

Resveratrol, a SIRT1 Activator, Ameliorates MK-801-Induced Cognitive and Motor Impairments in a Neonatal Rat Model of Schizophrenia

“…Another research showed that MK-801 administration also inhibited the phosphorylation of CREB in the rat hippocampus (33). CREB is the upstream transcription factor of BDNF and inhibited CREB phosphorylation downregulates BDNF expression (34). In the neonatal rat schizophrenia model induced by MK-801 administration, we observed the inhibited phosphorylation of CREB in the hippocampus.…”

Proteasome Inhibitor MG132 is Toxic and Inhibits the Proliferation of Rat Neural Stem Cells but Increases BDNF Expression to Protect Neurons

“…Using a dominant-negative CREB mutant, it has been identified that CREB signaling is essential for the survival and differentiation of newborn neurons [62][63][64]. In addition, CREB phosphorylation is known to increase BDNF expression [65][66][67]. In our study, we detected the activation of CREB phosphorylation and the induction of BDNF expression upon MG132 treatment.…”