Reduced exploratory behavior in neuronal nucleoredoxin knockout mice

  • Nucleoredoxin is a thioredoxin-like redoxin that has been recognized as redox modulator of WNT signaling. Using a Yeast-2-Hybrid screen, we identified calcium calmodulin kinase 2a, Camk2a, as a prominent prey in a brain library. Camk2a is crucial for nitric oxide dependent processes of neuronal plasticity of learning and memory. Therefore, the present study assessed functions of NXN in neuronal Nestin-NXN-/- deficient mice. The NXN-Camk2a interaction was confirmed by coimmunoprecipitation, and by colocalization in neuropil and dendritic spines. Functionally, Camk2a activity was reduced in NXN deficient neurons and restored with recombinant NXN. Proteomics revealed reduced oxidation in the hippocampus of Nestin-NXN-/- deficient mice, including Camk2a, further synaptic and mitochondrial proteins, and was associated with a reduction of mitochondrial respiration. Nestin-NXN-/- mice were healthy and behaved normally in behavioral tests of anxiety, activity and sociability. They had no cognitive deficits in touchscreen based learning & memory tasks, but omitted more trials showing a lower interest in the reward. They also engaged less in rewarding voluntary wheel running, and in exploratory behavior in IntelliCages. Accuracy was enhanced owing to the loss of exploration. The data suggested that NXN maintained the oxidative state of Camk2a and thereby its activity. In addition, it supported oxidation of other synaptic and mitochondrial proteins, and mitochondrial respiration. The loss of NXN-dependent pro-oxidative functions manifested in a loss of exploratory drive and reduced interest in reward in behaving mice.
Author:Bao Ngoc Tran, Lucie Valek, Annett Wilken-Schmitz, Dominik Christian FuhrmannORCiDGND, Dimitry Namgaladze, Ilka WittigORCiD, Irmgard TegederORCiD
Parent Title (English):Redox Biology
Place of publication:Amsterdam [u.a.]
Document Type:Article
Date of Publication (online):2021/06/23
Date of first Publication:2021/06/23
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2022/05/09
Tag:Behavior; Calcium calmodulin kinase; IntelliCage; Play; Pleasure; Proteomics; Redoxin
Issue:art. 102054
Page Number:20
First Page:1
Last Page:20
The study was supported by the Deutsche Forschungsgemeinschaft (SFB815, A12 to IT; SFB815, Z01 to IW; and CRC1080, C02 to IT).
Data availability statement: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [26] partner repository with the dataset identifier PXD024624.
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0