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Updated: May 12, 2026
Functional Calcium Imaging in Developing Cortical Networks
Published on: October 22, 2011
Calcium sensing receptor absence delays postnatal brain development via direct and indirect mechanisms
Xiu-Ling Liu1, Yu-Shan Lu, Jun-Ying Gao
1Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, 210029, People's Republic of China.
Abstract:
Calcium sensing receptor (CaSR) is implicated in the establishment of neural connections and myelin formation. However, its contribution to brain development remains unclear. We addressed this issue by analyzing brain phenotype in postnatal CaSR null mice, a model of human neonatal severe hyperparathyroidism. One- and 2-week-old CaSR null mice exhibited decreased brain weight and size with a developmental delay in expression of proliferating cell nuclear antigen. Neuronal and glial differentiation markers, neuronal specific nuclear protein, glial fibrillary acidic protein, and myelin basic protein, were also decreased compared with age-matched wild-type littermates. Moreover, deletion of the parathyroid hormone gene that corrects hyperparathyroidism, hypercalcemia, hypophosphatemia, and whole-body growth retardation normalized brain cell proliferation, but not differentiation, in CaSR null mice. Cultured neural stem cells (NSCs) derived from the subventricular zones of CaSR null neonatal mice exhibited normal proliferation capacity but decreased differentiation capacity, compared with wild-type controls. These results demonstrate that direct effects of CaSR absence impair NSC differentiation, while secondary effects of parathyroid hormone-related endocrine abnormalities impair NSC proliferation, both of which contribute to delayed brain development in CaSR null newborn mice.
Insights
The calcium sensing receptor (CaSR) is crucial for brain development. Its absence impairs neural stem cell differentiation and proliferation, leading to delayed brain growth in neonatal mice.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- The calcium sensing receptor (CaSR) plays a role in neural connections and myelination.
- Its precise contribution to overall brain development is not fully understood.
- CaSR null mice serve as a model for human neonatal severe hyperparathyroidism.
Purpose of the Study:
- To investigate the role of CaSR in brain development.
- To analyze the brain phenotype of postnatal CaSR null mice.
- To differentiate direct CaSR effects from secondary endocrine abnormalities.
Main Methods:
- Phenotypic analysis of CaSR null mice at one and two weeks post-birth.
- Assessment of brain weight, size, and cell proliferation markers (proliferating cell nuclear antigen).
- Evaluation of neuronal and glial differentiation markers (neuronal specific nuclear protein, glial fibrillary acidic protein, myelin basic protein) and neural stem cell (NSC) differentiation capacity.
Main Results:
- CaSR null mice showed reduced brain weight and size with delayed cell proliferation.
- Neuronal and glial differentiation markers were decreased in CaSR null mice.
- While correcting hyperparathyroidism normalized proliferation, NSC differentiation remained impaired, indicating direct CaSR effects.
Conclusions:
- Direct absence of CaSR impairs neural stem cell differentiation.
- Secondary effects of parathyroid hormone-related endocrine issues hinder neural stem cell proliferation.
- Both direct and indirect mechanisms contribute to delayed brain development in CaSR null mice.
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