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Effects on the fetal cholinergic basal forebrain following maternal immune activation
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Pratt, Lorelei. Effects on the fetal cholinergic basal forebrain following maternal immune activation. Retrieved from https://doi.org/doi:10.7282/T34Q7SQ5

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TitleEffects on the fetal cholinergic basal forebrain following
maternal immune activation
NamePratt, Lorelei (author); Jonakait, G Miller (chair); Morrell, Joan I (internal member); Friedman, Wilma (internal member); Ponzio, Nicholas M (outside member); DiCicco-Bloom, Emanuel (outside member); Rutgers University; Graduate School - Newark
Date Created2013
Other Date2013-01 (degree)
SubjectBiology, Maternal-fetal exchange, Parasympathomimetic agents, Interleukin-6, Fetus--Development
Extentx, 158 p. : ill.
DescriptionNeurodevelopmental disorders such as autism and schizophrenia may result in part from maternal immune activation (MIA) during pregnancy. However, the mechanisms in the embryonic brain leading to these disorders in offspring remain unclear. Data suggest that interleukin-6 (IL-6) may be a key factor affecting fetal development following MIA. Abnormalities in the cholinergic basal forebrain (BF) are associated with neurodevelopmental disorders. Previous in vitro studies have shown that factors produced by activated microglia promote the cholinergic differentiation of precursors in the BF. It has not been demonstrated whether fetal microglia become activated in vivo following MIA or whether such activation results in increased numbers of BF cholinergic neurons. To test this, pregnant wild-type and IL-6 knock-out mice were injected with a viral mimic. Fetal/perinatal BFs of offspring were assayed for choline acetyltransferase (ChAT) activity and compared to offspring of saline-injected mice. The number of cholinergic neurons in BFs was quantified using stereological techniques. To determine fetal microglial activation status, lysates from enriched populations of microglial cells were analyzed for cytokine/chemokine protein production using LUMINEX® assays. Studies were performed in culture to determine whether certain elevated chemokines affect BF cholinergic development. Results show that following MIA, ChAT activity increases in the BF at embryonic days 16.5 (E16.5), E18.5 and postnatal day 1 (P1). Cholinergic cell number also increases. Fetal microglia produce higher levels of several cytokines and chemokines. Unexpectedly, ChAT activity is higher in control IL-6 KO BFs at E16.5 than in wild-types and MIA does not increase ChAT activity further. Non-microglial fetal brain cells also produce cytokines and chemokines. Non-microglial cells from control IL-6 KOs express increased levels of cytokines and chemokines compared to wild-types and MIA does not increase these levels. Culture studies suggest that a C-C chemokine receptor 5 (CCR5) ligand may be a factor affecting BF cell survival. These data reveal changes following MIA that could potentially affect neural development. The fetal microglial cytokine/chemokine profile is altered. Perinatal increases in ChAT activity may have long-lasting consequences. Results also suggest a role for IL-6 in regulating proper cytokine and chemokine balance during normal brain development.
NotePh.D.
NoteIncludes bibliographical references
NoteIncludes vita
Noteby Lorelei Pratt
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T34Q7SQ5
Languageeng
CollectionGraduate School - Newark Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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