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Dusp8 affects hippocampal size and behavior in mice and humans
Peter Baumann1,2,3, Sonja C Schriever1,2,3, Stephanie Kullmann3,4,5
1Research Unit Neurobiology of Diabetes, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
Scientific Reports
|December 22, 2019
Summary
Dual-specificity phosphatase 8 (Dusp8) deficiency impairs spatial learning and increases anxiety in mice. Human carriers of a DUSP8 variant show reduced hippocampal volume, suggesting a conserved role in brain function.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Dual-specificity phosphatase 8 (Dusp8) regulates mitogen-activated protein kinases (MAPKs) crucial for central nervous system (CNS) processes.
- Dusp8 is highly expressed in the hippocampus, yet its specific functions there remain largely unknown.
Purpose of the Study:
- To investigate the role of Dusp8 in hippocampal morphology, MAPK signaling, neurogenesis, apoptosis, and behavior.
- To determine if human DUSP8 variants are associated with similar hippocampal alterations observed in Dusp8-deficient mice.
Main Methods:
- Comparison of Dusp8 wild-type (WT) and knockout (KO) mouse littermates.
- Assessment of spatial learning, locomotor activity, anxiety, cell proliferation, apoptosis, and MAPK phosphorylation (Erk, Jnk, p38) in mouse hippocampi.
- Analysis of hippocampal subregion volumes in Dusp8 KO mice and correlation with human SNP rs2334499 in human carriers.
Main Results:
- Dusp8 KO mice exhibited impaired spatial learning, increased locomotor activity, and heightened anxiety.
- No significant changes in cell proliferation, apoptosis, or p38/Jnk phosphorylation were observed.
- Elevated phospho-Erk levels and reduced hippocampus size, specifically subiculum and CA4, were found in Dusp8 KO mice.
- Human carriers of the DUSP8 variant (SNP rs2334499:C>T) showed decreased hippocampal volumes.
Conclusions:
- Dusp8 plays a significant role in regulating hippocampus morphology and associated behaviors.
- Findings in Dusp8 KO mice translate to human carriers of specific DUSP8 variants, indicating a conserved function.
- Dusp8 is a novel, translationally relevant factor in hippocampus function and limbic network regulation.
