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Calcium-containing endosomes at oculomotor terminals in animal models of ALS
L Siklós1, J I Engelhardt, R Adalbert
1Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
Altered calcium homeostasis has been demonstrated in human spinal cord motor axon terminals of ALS patients, in spinal motor neurons of mutant SOD transgenic mice and following injection of ALS immunoglobulins. In all three paradigms oculomotor neurons are relatively spared. To explore mechanisms of selective resistance, we applied similar calcium localization techniques to terminals of oculomotor neurons in the two animal models. In both cases large vacuoles, which connect with the extracellular space, accumulated the majority of intracellular calcium, while terminals of vulnerable neurons (e.g. innervating interosseus muscle), which possess no such vacuoles, displayed evenly distributed calcium. These relatively unique membrane enveloped structures may permit neurons to control their cytoplasmic Ca2+ concentration and contribute to selective resistance.
Insights
Motor neuron disease involves calcium imbalance. Unique vacuoles in spared oculomotor neurons may protect them by sequestering excess calcium, offering insights into neuroprotection strategies.
Area of Science:
- Neuroscience
- Cell Biology
- Neurodegenerative Diseases
Background:
- Altered calcium homeostasis is implicated in Amyotrophic Lateral Sclerosis (ALS).
- Motor neuron terminals in ALS patients and mouse models show calcium dysregulation.
- Oculomotor neurons are notably resistant to these effects.
Purpose of the Study:
- To investigate the mechanisms underlying the selective resistance of oculomotor neurons in ALS models.
- To compare calcium distribution in resistant oculomotor neurons versus vulnerable motor neurons.
Main Methods:
- Calcium localization techniques were applied to oculomotor neuron terminals.
- Comparison of calcium distribution in oculomotor neurons and vulnerable motor neurons (e.g., interosseus muscle innervating) in ALS models.
Main Results:
- Vulnerable neurons exhibited evenly distributed intracellular calcium.
- Resistant oculomotor neurons showed significant calcium accumulation within large vacuoles.
- These vacuoles were observed to connect with the extracellular space.
Conclusions:
- Large, membrane-enveloped vacuoles in oculomotor neurons may play a role in regulating cytoplasmic calcium levels.
- These structures could contribute to the selective resistance observed in oculomotor neurons against ALS-related pathology.