Calcium sensing receptor absence delays postnatal brain development via direct and indirect mechanisms

Xiu Ling Liu, Yu Shan Lu, Jun Ying Gao, Charles Marshall, Ming Xiao, Deng Shun Miao, Andrew Karaplis, David Goltzman, Jiong Ding

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


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.

Original languageEnglish
Pages (from-to)590-600
Number of pages11
JournalMolecular Neurobiology
Issue number3
StatePublished - Dec 2013

Bibliographical note

Funding Information:
Acknowledgments This work was supported by grants from the National Nature and Scientific Foundation of China (no. 81271210 and no. 81230009), PAPD Foundation of Jiangsu Higher Education Institutions, and Qing Lan Project. We would like to thank Professor Edward Brown in the Brigham and Women’s Hospital, Harvard Medical School for providing CaSR+/− mice. We thank Dr. Hui Kong for excellent work on culturing neural stem cells.


  • Brain development
  • Calcium sensing receptor
  • Gene knockout
  • Neural stem cells
  • Parathyroid hormone

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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