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Stereotactic Injection of MicroRNA-expressing Lentiviruses to the Mouse Hippocampus CA1 Region and Assessment of the Behavioral Outcome
Published on: June 10, 2013
Hippocampal miRNA-144 Modulates Depressive-Like Behaviors in Rats by Targeting PTP1B
Yuhuan Li1, Nina Wang2, Jie Pan2
1Department of Psychology, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People's Republic of China.
Background:
Depression is the common mental disorder in the world. However, the pathophysiology mechanism underlying depression remains elusive. It has been reported that aberrant expression of miR-144 is closely related to depression. This study was to investigate whether and how miR-144 involves in depressive-like behaviors in a chronic unpredictable mild stress (CUMS) animal model.
Methods:
A rat model of CUMS was established, and qRT-PCR was performed to detect the expression of miR-144 in the hippocampus of a depressed rat. The lentiviral vector carried miR-144 (LV-miR-144) was injected into the hippocampus of the CUMS rat to investigate the effects of miR-144 on the behaviors and PTP1B/TrkB/BDNF signal transduction in the hippocampus of the rat. The interaction between miR-144 and PTP1B was investigated by biological analyses and dual-luciferase reporter assay.
Results:
The results showed that CUMS rats had typical depressive behaviors, and the expression of miR-144 in the hippocampus of CUMS rats was significantly lower than that of the control group. In addition, PTP1B protein expression was significantly up-regulated, while the expression of pTrkB and BDNF protein was significantly down-regulated in the hippocampus of CUMS rats. Moreover, PTP1B was a direct target of miR-144, and miR-144 could activate the downstream TrkB/BDNF signaling pathway by inhibiting the expression of PTP1B in primary hippocampus neurons.
Conclusion:
MiR-144 played an anti-depressive role in hippocampus dysfunction by inhibiting PTP1B and activating the TrkB/BDNF signaling pathway in the hippocampus of CUMS rats.
Insights
MicroRNA-144 (miR-144) shows anti-depressive effects by inhibiting PTP1B and activating the TrkB/BDNF pathway in the hippocampus. This study explores its role in a chronic unpredictable mild stress depression model.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Depression is a prevalent mental disorder with unclear pathophysiology.
- Aberrant microRNA-144 (miR-144) expression is linked to depression.
- Understanding miR-144's role is crucial for developing novel depression therapies.
Purpose of the Study:
- To investigate the involvement of miR-144 in depressive-like behaviors.
- To elucidate the molecular mechanisms of miR-144 in a chronic unpredictable mild stress (CUMS) rat model.
- To determine the effect of miR-144 on the PTP1B/TrkB/BDNF signaling pathway.
Main Methods:
- Established a CUMS rat model to induce depressive behaviors.
- Quantified miR-144 expression in the hippocampus using qRT-PCR.
- Utilized lentiviral vectors to manipulate miR-144 levels and assessed behavioral and molecular changes.
- Investigated the interaction between miR-144 and PTP1B via biological assays and dual-luciferase reporter assay.
Main Results:
- CUMS rats exhibited depressive behaviors and significantly reduced hippocampal miR-144 expression.
- Hippocampal PTP1B protein was upregulated, while pTrkB and BDNF were downregulated in CUMS rats.
- miR-144 directly targets PTP1B, inhibiting its expression and activating the TrkB/BDNF pathway in hippocampal neurons.
Conclusions:
- MiR-144 exerts an anti-depressive role in the hippocampus.
- Inhibition of PTP1B by miR-144 is a key mechanism underlying its antidepressant effects.
- Activation of the TrkB/BDNF signaling pathway by miR-144 contributes to alleviating hippocampus dysfunction in depression.
