Spatial learning and long-term memory impairments in RasGrf1 KO, Pttg1 KO, and double KO mice

Abstract

Background: RasGrf1 is a guanine-nucleotide releasing factor that enhances Ras activity. Human PTTG1 is an oncoprotein found in pituitary tumors and later identified as securin, a protein isolated from yeast with a reported role in chromosome separation. It has been suggested that RasGrf1 is an important upstream component of signal transduction pathways regulating Pttg1 expression and controlling beta cell development and their physiological response. At memory formation level, there are contradictory data regarding the role of RasGrf1, while Pttg1 has not been previously studied. Both proteins are expressed in the mammalian hippocampus, which is one of the key brain areas for spatial learning and memory.

Objective: The aim of this work was to study a potential link between RasGrf1 and Pttg1 in memory formation.

Method: Spatial learning and memory test in the Pttg1 KO, RasGrf1 KO, and Pttg1-RasGrf1 double KO and their correspondent WT mice using a Barnes maze.

Results: In comparison with the WT control mice, Pttg1 KO mice learned how to solve the task in a less efficient way, suggesting problems in memory consolidation. RasGrf1 KO mice performance was similar to controls, and they learned to use the best searching strategy. Double KO mice reached a better spatial learning level than WT.

Conclusion: A role for Pttg1 in memory consolidation/formation is suggested, while our RasGrf1 KO mice do not show hippocampus associated memory defects.

Keywords: Barnes maze; PCA; Pttg1; RasGrf1; memory; spatial learning.