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Androgen mitigates axotomy-induced decreases in calbindin expression in motor neurons
1Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Abstract:
Androgens can rescue axotomized motor neurons from cell death. Here we examine a possible mechanism for this trophic action in juvenile Xenopus laevis: regulation of a calcium-binding protein, calbindin, after axotomy. Western analysis revealed that a monoclonal antibody to calbindin D specifically recognizes a single approximately 28 kDa band in X. laevis CNS and rat cerebellum. Retrograde transport of peroxidase combined with immunohistochemistry demonstrated that somata, axons, and synaptic terminals of laryngeal motor neurons in nucleus (N.) IX-X of X. laevis are calbindin-positive. The number of calbindin-positive cells was compared in the intact and axotomized sides of N.IX-X of gonadectomized males that were either hormonally untreated or DHT-treated for 1 month. Although axotomy decreased the number of calbindin-positive cells by 86% in hormonally untreated males, the decrease was only 56% in DHT-treated animals. Compared with hormonally untreated animals, the number of calbindin-labeled cells in N.IX-X of DHT-treated males was increased in both the intact (14%) and axotomized sides (75%). We conclude that axotomy decreases and that DHT enhances calbindin immunoreactivity in N.IX-X. Axotomy-induced decrease in calbindin immunoreactivity precedes cell loss in N.IX-X and may impair the capacity of motor neurons to regulate cytoplasmic calcium. Androgen-mediated maintenance of calbindin expression is thus a candidate cellular mechanism for trophic maintenance of hormone target neurons.
Insights
Androgens protect motor neurons from death by regulating calbindin. Dihydrotestosterone (DHT) treatment maintained calbindin levels after nerve injury, suggesting a mechanism for neuroprotection.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Androgens are known to protect motor neurons from cell death after injury.
- The precise molecular mechanisms underlying this neuroprotective effect are not fully understood.
- Calbindin, a calcium-binding protein, is implicated in neuronal survival.
Purpose of the Study:
- To investigate the role of calbindin regulation in androgen-mediated neuroprotection of axotomized motor neurons in Xenopus laevis.
- To determine if androgens influence calbindin expression in motor neurons following axotomy.
Main Methods:
- Western analysis was used to confirm antibody specificity for calbindin D.
- Immunohistochemistry combined with retrograde transport of peroxidase identified calbindin-positive motor neurons in the nucleus (N.) IX-X.
- Calbindin-positive cell counts were compared between intact and axotomized sides in hormonally untreated and DHT-treated gonadectomized male Xenopus.
Main Results:
- Axotomy significantly decreased calbindin-positive cells by 86% in untreated males, but only by 56% in DHT-treated males.
- DHT treatment increased calbindin-labeled cells by 14% in intact N.IX-X and by 75% in axotomized N.IX-X compared to untreated animals.
- The reduction in calbindin immunoreactivity preceded cell loss and may impair calcium regulation.
Conclusions:
- Axotomy reduces calbindin immunoreactivity in motor neurons, potentially compromising calcium homeostasis.
- Dihydrotestosterone (DHT) enhances calbindin expression in motor neurons, both in intact and axotomized states.
- Androgen-dependent maintenance of calbindin is a potential cellular mechanism for the trophic support of motor neurons.