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Transient intrauterine ischemia duringmid‐gestation results in postnatal abnormalities in formation of neocorticalcircuit elements (981.11)
Author(s) -
Sandhu Sonia,
Kraushar Matthew,
Wijeratne Sagara,
Rasin MladenRoko
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.981.11
Subject(s) - neocortex , forebrain , biology , immunostaining , dendritic spine , neuroscience , ischemia , cerebral cortex , pathology , immunohistochemistry , microbiology and biotechnology , endocrinology , anatomy , medicine , central nervous system , hippocampal formation , immunology
The mammalian neocortex is six‐layered brain structure responsible for higher cognitive functions, voluntary motor behavior, and perception. The differentiation of neocortical projection neurons into each layer requires an uninterrupted coordination of functional gene expression, which may be susceptible to insults like transient intrauterine ischemia (TII). We developed a model of TII in an anesthetized gravid mouse at E15 for 15 minutes. Previously conducted cortical layer‐marker studies of CDP, a transcription factor associated with post‐mitotic dendritic differentiation, showed expanded expression in Ischemic mice relative to Sham mice. Decreased expression of CTIP2, associated with formation of striatal sub‐cortical tracts and L1‐NCAM immunostaining of forebrain axonal pathways in Ischemic brains relative to Sham suggesting further that TII at E15 induces disrupted expression of key genes in the development of neocortical layers. We used Golgi Staining and a digital quantification program to analyze ultrastructure changes in upper and lower layer neurons in both male and female mice in dendritic spine density, dendritic branching, axonal lengths, and cell body size in 8‐week old adult mice for Ischemic and Sham conditions. Remarkably, profound differences in dendritic complexity and dendritic spine density differences were seen postnatally in cytoarchitecture, suggesting that TII is sufficient to cause abnormalities in neocortical circuit elements and implications of neurodevelopmental diseases, such as Schizophrenia.