Pyruvate kinase M2 (PKM2) improve symptoms of post-ischemic stroke depression by activating VEGF to mediate the MAPK/ERK pathway.

Abstract

PURPOSE:

To evaluate and identify the effects and explore the mechanisms of pyruvate kinase M2 (PKM2) on stroke-induced post stroke depression (PSD).

METHODS:

Rats were separated into six different groups, including sham + saline, Stroke + saline, PSD + saline, PSD + recombinant pyruvate kinase M2 (rPKM2) (112 ng/kg), PSD + rPKM2 (224 ng/kg), and PSD + rPKM2 (224 ng/kg) + bevacizumab. Then, the body weight, sucrose preference rate, immobility time, horizontal movement, and vertical movement were determined to evaluate the effect of PKM2 on improving the depressive behavior of PSD rats. Subsequently, the proliferation of oligodendrocytes in subventricular zone (SVZ) of rats in each group was examined by western blot and immunofluorescent staining. Furthermore, the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were also detected by qPCR and ELISA to verify the anti-inflammatory effects of PKM2 on PSD rats. In addition, the protein expression levels of MDA, LDH, and NO were tested to reveal that PKM2 can reduce oxidative stress in PSD rats. The western blot and IHC assays were employed to examine the protein expression levels of VEGF, PKM2, and ERK in PSD rats.

RESULTS:

In this study, the results showed that PKM2 can improve the depressive behavior and proliferation of oligodendrocytes in PSD rats. In addition, PKM2 has anti-inflammatory and anti-oxidative stress effects on PSD rats. Meanwhile, PKM2 activated the expression level of VEGF/MAPK/ERK pathway.

CONCLUSION:

PKM2 improves symptoms of post-ischemic stroke depression by activating VEGF-mediated MAPK/ERK pathway.

• Authors: Yun Feng, Xuebin Li, Jie Wang, Xiaohua Huang, Lanqing Meng, Jianmin Huang
• Journal: Brain and behavior (Brain Behav) Vol. 12 Issue 1 Pg. e2450 (01 2022) ISSN: 2162-3279 [Electronic] United States
• PMID: 34898024 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

Chemical References

• Recombinant Proteins
• Vascular Endothelial Growth Factor A
• Pyruvate Kinase

Topics

• Animals
• Depression (drug therapy, etiology)
• Ischemic Stroke
• MAP Kinase Signaling System
• Pyruvate Kinase (metabolism, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins
• Vascular Endothelial Growth Factor A (metabolism)