Nedl1 knockout impaired the learning and memory of mice

Abstract

Background

Protein ubiquitination is a common post-translational modification involved in protein degradation and various life processes in cells. NEDL1 is a ubiquitin ligase that is highly expressed primarily in the brain. However, the functions of NEDL1 in social approach/novelty preference, anxiety, learning and memory remain poorly understood.

Methods

Nedl1 knockout mice (Nedl1^−/−) and wild-type mice (Nedl1^+/+) were tested using three-chamber test, elevated plus maze, and Barnes maze. Then, brain tissue was stained, and blood was collected for metabolic analysis.

Results

Compared with Nedl1^+/+ mice, Nedl1^−/− mice showed no differences in social approach/novelty preference and anxiety behavior. Nedl1^−/− mice displayed impaired learning and memory. Nedl1 knockout did not affect the number of neurons and oligodendrocytes in the hippocampus. Astrocytes proliferated in the hippocampus of Nedl1^−/− mice. The amino acid metabolism of Nedl1^+/+and Nedl1^−/− mice is different, especially the increase in proline and tryptophan.

Conclusion

This study showed that Nedl1 knockout impaired learning and memory, which may be related to astrocyte proliferation and amino acid metabolism change. Nedl1 knockout did not affect social style/novelty preference and anxiety behavior in mice. The preliminary study of NEDL1 in neurobehavioral function could help understand the role of NEDL1 in the nervous system.