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ISDN2012_0289: Altered neurotransmitter levels in different regions of rat brain following acute stress
Author(s) -
Shameem Mohammad,
Wadhwa Meetu,
Shukla Shubha
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.2012.10.060
Subject(s) - library science , pharmacology , medicine , computer science
Lakshmi Subramanian 1, Anindita Sarkar 1, Ashwin S. Shetty 1, Bhavana Muralidharan 1, Hari Padmanabhan 1, Michael Piper 2, Edwin S. Monuki 3, Ingolf Bach 4, Richard M. Gronostajski 5,6, Linda J. Richards 2, Shubha Tole 2 1 Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India 2 Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia 3 Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Irvine, CA 92697, United States 4 Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States 5 Department of Biochemistry, State University of New York, Buffalo, NY 14203, United States 6 Developmental Genomics Group, New York State Centre of Excellence in Bioinformatics and Life Sciences, Buffalo, NY 14203, United States The sequential production of neurons and astrocytes from neuroepithelial precursors is a fundamental feature of central nervous system development. We report that LIM-homeodomain (LIM-HD) transcription factor Lhx2 regulates this transition in the developing hippocampus. Disrupting Lhx2 function in the embryonic hippocampus by in utero electroporation and in organotypic slice culture caused the premature production of astrocytes at stages when neurons are normally generated. Lhx2 function is therefore necessary to suppress astrogliogenesis during the neurogenic period. Furthermore, Lhx2 overexpression was sufficient to suppress astrogliogenesis and prolong the neurogenic period. We provide evidence that Lhx2 overexpression can counteract the instructive astrogliogenic effect of Notch activation. Lhx2 overexpression was also able to override and suppress the activation of the GFAP promoter by Nfia, a Notch-regulated transcription factor that is required for gliogenesis. Thus, Lhx2 appears to act as a “brake” on Notch/Nfia-mediated astrogliogenesis. This critical role for Lhx2 is spatially restricted to the hippocampus, because loss of Lhx2 function in the neocortex did not result in premature astrogliogenesis at the expense of neurogenesis. Our results therefore place Lhx2 as a central regulator of the neuron-glia cell fate decision in the hippocampus and reveal a striking regional specificity of this fundamental function within the dorsal telencephalon.