Back to Search
Start Over
Nuclear receptor binding factor 2 (NRBF2) is required for learning and memory
- Source :
- Laboratory investigation; a journal of technical methods and pathology. 100(9)
- Publication Year :
- 2019
-
Abstract
- The mechanisms which underlie defects in learning and memory are a major area of focus with the increasing incidence of Alzheimer's disease in the aging population. The complex genetically-controlled, age-, and environmentally-dependent onset and progression of the cognitive deficits and neuronal pathology call for better understanding of the fundamental biology of the nervous system function. In this study, we focus on nuclear receptor binding factor-2 (NRBF2) which modulates the transcriptional activities of retinoic acid receptor α and retinoid X receptor α, and the autophagic activities of the BECN1-VPS34 complex. Since both transcriptional regulation and autophagic function are important in supporting neuronal function, we hypothesized that NRBF2 deficiency may lead to cognitive deficits. To test this, we developed a new mouse model with nervous system-specific knockout of Nrbf2. In a series of behavioral assessment, we demonstrate that NRBF2 knockout in the nervous system results in profound learning and memory deficits. Interestingly, we did not find deficits in autophagic flux in primary neurons and the autophagy deficits were minimal in the brain. In contrast, RNAseq analyses have identified altered expression of genes that have been shown to impact neuronal function. The observation that NRBF2 is involved in learning and memory suggests a new mechanism regulating cognition involving the role of this protein in regulating networks related to the function of retinoic acid receptors, protein folding, and quality control.
- Subjects :
- 0301 basic medicine
Nervous system
Male
Retinoic acid
Autophagy-Related Proteins
Mice, Transgenic
Biology
Retinoid X receptor
Motor Activity
Pathology and Forensic Medicine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Memory
medicine
Transcriptional regulation
Animals
Learning
Receptor
Maze Learning
Molecular Biology
Cells, Cultured
Regulation of gene expression
Mice, Knockout
Neurons
Memory Disorders
Learning Disabilities
Brain
Cell Biology
Mice, Inbred C57BL
Retinoic acid receptor
030104 developmental biology
medicine.anatomical_structure
chemistry
Nuclear receptor
Gene Expression Regulation
Organ Specificity
030220 oncology & carcinogenesis
Trans-Activators
Neuroscience
Subjects
Details
- ISSN :
- 15300307
- Volume :
- 100
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Laboratory investigation; a journal of technical methods and pathology
- Accession number :
- edsair.doi.dedup.....3b403b5cb7904e50e31e8e825239bc4d