Related Experiment Video
Updated: Jun 13, 2026
06:54
Quantifying Spontaneous Ca2+ Fluxes and their Downstream Effects in Primary Mouse Midbrain Neurons
Published on: September 9, 2020
Enhanced calcium activity and transcriptomic alterations in iPSC-derived neurons from BAFME patients with repeat
Yuki Nagasako1, Mitsuru Ishikawa2, Hiroyuki Ishiura3
1Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
Neuroscience Research
|June 11, 2026
Summary
Benign adult familial myoclonus epilepsy (BAFME) involves repeat expansions in SAMD12. Patient-derived neurons show heightened activity and altered signaling, suggesting subtype-specific changes contribute to epilepsy.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Benign adult familial myoclonus epilepsy (BAFME) is linked to repeat expansions in SAMD12 and other genes.
- The underlying neuronal mechanisms of cortical hyperexcitability in BAFME remain poorly understood.
Purpose of the Study:
- To investigate the functional and transcriptomic phenotypes of neurons derived from BAFME patients.
- To elucidate the neuronal basis of cortical hyperexcitability in BAFME.
Main Methods:
- Generated induced pluripotent stem cell (iPSC)-derived glutamatergic and GABAergic neurons from BAFME patients.
- Performed calcium imaging, pharmacological profiling, and RNA sequencing.
Main Results:
- Patient-derived neurons exhibited pathogenic repeat expansions and increased spontaneous Ca2+ transient frequency.
- Altered responses to AMPA-type glutamate receptor blockade and GABA(A) receptor antagonism were observed.
- RNA sequencing revealed subtype-specific transcriptomic alterations, including downregulation of SLC7A5 in glutamatergic neurons and upregulation of PTPRD and GPC6 in GABAergic neurons.
Conclusions:
- Subtype-specific neuronal alterations contribute to hyperexcitability in BAFME.
- These findings offer a cellular model for studying repeat expansion-associated epilepsies.
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