Nedl1 knockout impaired the learning and memory of mice.

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.
Competing Interests: Declaration of competing interests The authors have no competing interests.
(Copyright © 2024. Published by Elsevier Inc.)