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Updated: Mar 23, 2026
Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior and memory deficits in mouse
K Fujiwara1,2, Y Fujita1,2, A Kasai3
1Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.
Abstract:
JMJD2B is a histone demethylase enzyme that regulates gene expression through demethylation of H3K9me3. Although mutations of JMJD2B have been suggested to be responsible for neurodevelopmental disorders, the function of JMJD2B in the central nervous system (CNS) remains to be elucidated. Here we show that JMJD2B has a critical role in the development of the CNS. We observed JMJD2B expression, which was especially strong in the hippocampus, throughout the CNS from embryonic periods through adulthood. We generated neuron-specific JMJD2B-deficient mice using the cre-loxP system. We found an increase in total spine number, but a decrease in mature spines, in the CA1 region of the hippocampus. JMJD2B-deficient mice exhibited hyperactive behavior, sustained hyperactivity in a novel environment, deficits in working memory and spontaneous epileptic-like seizures. Together these observations indicate that JMJD2B mutant mice display symptoms reminiscent of neurodevelopmental disorders. Our findings provide evidence for the involvement of histone demethylation in the formation of functional neural networks during development.
Insights
JMJD2B, a histone demethylase, is crucial for central nervous system (CNS) development. Its deficiency in neurons leads to neurodevelopmental disorder symptoms, including memory deficits and seizures.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- JMJD2B is a histone demethylase regulating gene expression via H3K9me3 demethylation.
- Mutations in JMJD2B are linked to neurodevelopmental disorders, but its CNS function is unclear.
Purpose of the Study:
- To investigate the role of JMJD2B in central nervous system (CNS) development.
- To elucidate the function of JMJD2B in neuronal development and network formation.
Main Methods:
- Studied JMJD2B expression in the CNS from embryonic stages to adulthood.
- Generated neuron-specific JMJD2B-deficient mice using the cre-loxP system.
- Analyzed hippocampal spine morphology and behavioral phenotypes.
Main Results:
- JMJD2B is expressed throughout the CNS, particularly in the hippocampus.
- Neuron-specific JMJD2B deficiency resulted in increased total spines but decreased mature spines in the hippocampus.
- JMJD2B-deficient mice exhibited hyperactivity, working memory deficits, and epileptic seizures.
Conclusions:
- JMJD2B plays a critical role in CNS development and the formation of functional neural networks.
- JMJD2B deficiency in neurons recapitulates key features of neurodevelopmental disorders.
- Histone demethylation is essential for proper neural network development.
