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Fluorescent Calcium Imaging and Subsequent In Situ Hybridization for Neuronal Precursor Characterization in Xenopus laevis
Published on: February 18, 2020
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Primary cortical neurons precipitate and extrude large mitochondria-associated calcium-phosphate sheets with a
Erik D Anderson1, Christopher A Cronkite1,2, Philip R Baldwin1
1Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.
Biorxiv : the Preprint Server for Biology
|August 13, 2025
Summary
Mitochondria in neurons can form octacalcium phosphate structures, potentially contributing to brain calcification in diseases like Alzheimer's. These structures are extruded via migrasomes, offering new therapeutic targets.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Pathological calcium-phosphate buildup in the brain is linked to neurological disorders.
- Mitochondria are suspected sources of extracellular calcium-phosphate in the nervous system.
- Unidentified aggregates were observed in Huntington's disease model neurons.
Purpose of the Study:
- To identify the composition and origin of unidentified aggregates in neurons.
- To investigate the role of mitochondria in neuronal calcium-phosphate regulation.
- To explore potential therapeutic targets for neurological calcification disorders.
Main Methods:
- Cryo-electron tomography (cryo-ET)
- Cryo-correlative light and electron microscopy (cryo-CLEM)
- Low-dose electron energy loss spectroscopy (LDSAED)
- Isolation of wild-type cortical neurons from embryonic day 18 rat embryos
Main Results:
- Identified sheet aggregates with an octacalcium phosphate-like structure in wild-type neurons.
- Demonstrated that these aggregates are derived from mitochondria.
- Showed that aggregates are extruded, at least in part, by migrasomes.
- Confirmed absence of these aggregates in control neurons.
Conclusions:
- Mitochondria serve as reservoirs for intracellular and extracellular calcium-phosphate.
- Neuronal migrasomes are involved in the extrusion of calcium-phosphate aggregates.
- These findings highlight mitochondria as potential therapeutic targets for neurological disorders involving pathological calcification, such as Alzheimer's disease.
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