Peptide fragment of thymosin β4 increases hippocampal neurogenesis and facilitates spatial memory

• DOI: 10.1016/j.neuroscience.2015.09.017
• Publication Date: 2015-09-11T18:24:59Z
• Authors: D.H. Kim; E.-Y. Moon; J.H. Yi; H.E. Lee; S.J. Park; Y.-K. Ryu; H.-C. Kim; S. Lee; J.H. Ryu
• Keywords: Doublecortin Domain Proteins; Male; 0301 basic medicine; Neurogenesis; Neuropeptides; Cell Count; Hippocampus; 3. Good health; Mice, Inbred C57BL; Glycogen Synthase Kinase 3; Mice; 03 medical and health sciences; Neuroprotective Agents; Gene Expression Regulation; Phosphopyruvate Hydratase; Glial Fibrillary Acidic Protein; Animals; Humans; Maze Learning; Microtubule-Associated Proteins; Oligopeptides; Cell Proliferation; HeLa Cells

Although several studies have suggested the neuroprotective effect of thymosin β4 (TB4), a major actin-sequestering protein, on the central nervous system, little is understood regarding the action of N-acetyl-serylaspartyl-lysyl-proline (Ac-SDKP), a peptide fragment of TB4 on brain function. Here, we examined neurogenesis-stimulative effect of Ac-SDKP. Intrahippocampal infusion of Ac-SDKP facilitated the generation of new neurons in the hippocampus. Ac-SDKP-treated mouse hippocampus showed an increase in β-catenin stability with reduction of glycogen synthase kinase-3β (GSK-3β) activity. Moreover, inhibition of vascular endothelial growth factor (VEGF) signaling blocked Ac-SDKP-facilitated neural proliferation. Subchronic intrahippocampal infusion of Ac-SDKP also increased spatial memory. Taken together, these data demonstrate that Ac-SDKP functions as a regulator of neural proliferation and indicate that Ac-SDKP may be a therapeutic candidate for diseases characterized by neuronal loss.