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Neurobehavioral modifications following arsenic exposure in developing rats
Author(s) -
Parthiv Haldipur,
Subashika Govindan,
Upasna Bharti,
Chitra,
Sarkar,
Soumya Iyengar,
Pierre Gressens,
Shyamala Mani
Publication year - 2012
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2012.03.266
Subject(s) - arsenic , neuroscience , psychology , biology , chemistry , organic chemistry
E-mail address: g.subashika@gmail.com (S. Govindan). Introduction: The regulation of cell proliferation in the external granular layer (EGL) of the developing cerebellum is important for its normal patterning. An important signal that regulates EGL cell proliferation is Sonic hedgehog (Shh). Shh is secreted by the Purkinje cells (PC) and has a mitogenic effect on the granule cell precursors of the EGL. Deregulation of Shh signaling has been associated with abnormal development and been implicated in medulloblastomas, tumors that arise from the cerebellum. Methods: We have studied the expression pattern of Shh, its receptors patched and smoothened, and its effectors that belong to the Gli family of transcription factors during normal human cerebellum development from 10 weeks of gestational age to 5 years post natal age and in medulloblastomas, using immunohistochemistry, RT-PCR and western blot analyses. This expression pattern is compared to equivalent stages in the normal development of cerebellum in mouse as well as in tumors. Results: We find important differences between human and mouse that reflect differences in the normal developmental program between the two species. First, in humans there appears to be a stage of Shh signaling within the EGL when the PC are not yet the source of Shh. Secondly, unlike in the postnatal mouse cerebellum, the expression of Shh in the PC in postnatal human cerebellum is downregulated. Finally, medulloblastomas in the human but not in patched heterozygote mouse express Shh. Discussion: Given the importance of the Shh pathway in cerebellum development and disease there has been no prior systematic study of its expression pattern during human cerebellum development. Our results highlight cross species differences in the regulation of the Shh signaling pathway, and a possible role in the formation of medulloblastomas.