• the Korean Society for Brain and Neural Sciences


Original Article

Exp Neurobiol 2017; 26(1): 25-32

Published online February 28, 2017

© The Korean Society for Brain and Neural Sciences

Astrocytic Expression of CTMP Following an Excitotoxic Lesion in the Mouse Hippocampus

Nara Shin1,6, Min-Hee Yi2, Sena Kim1, Hyunjung Baek3, Ursula L. Triantafillu4, Jongsun Park5,6,* and Dong Woon Kim1,6,*

1Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon 35015, Korea, 2Department of Neuroscience & Cell Biology, the University of Texas Medical Branch School of Medicine, Galveston, TX 77555 USA, 3Department of Physiology, Brain Research Institute, Chungnam National University School of Medicine, Daejeon 35015, Korea, 4Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, USA, 5Department of Pharmacology, Chungnam National University School of Medicine, 6Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea

Correspondence to: *To whom correspondence should be addressed.
Jongsun Park
TEL: 82-42-580-8252, FAX: 82-42-585-6627
Dong Woon Kim
TEL: 82-42-580-8201 FAX: 82-42-586-4800

Received: September 15, 2016; Revised: December 2, 2016; Accepted: December 7, 2016


Akt (also known as protein kinase B, PKB) has been seen to play a role in astrocyte activation of neuroprotection; however, the underlying mechanism on deregulation of Akt signaling in brain injuries is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following kainic acid (KA)-induced neurodegeneration of mouse hippocampus. In control mice, there was a weak signal for CTMP in the hippocampus, but CTMP was markedly increased in the astrocytes 3 days after KA treatment. To further investigate the effectiveness of Akt signaling, the phosphorylation of CTMP was examined. KA treatment induced an increased p-CTMP expression in the astrocytes of hippocampus at 1 day. LPS/IFN-γ-treatment on primary astrocytes promoted the p-CTMP was followed by phosphorylation of Akt and finally upregulation of CTMP and p-CREB. Time-dependent expression of p-CTMP, p-Akt, p-CREB, and CTMP indicate that LPS/IFN-γ-induced phosphorylation of CTMP can activate Akt/CREB signaling, whereas lately emerging enhancement of CTMP can inhibit it. These results suggest that elevation of CTMP in the astrocytes may suppress Akt activity and ultimately negatively affect the outcome of astrocyte activation (astroglisiois). Early time point enhancers of phosphorylation of CTMP and/or late time inhibitors specifically targeting CTMP may be beneficial in astrocyte activation for neuroprotection within treatment in neuroinflammatory conditions.

Keywords: CTMP, Phosphorylation of CTMP, Akt, Astrocyte, Hippocampus