title: Decreased cortical serotonin in neonatal rabbits exposed to endotoxin in utero.
abstract: Maternal intrauterine inflammation is implicated in neurodevelopmental disorders in the offspring. Serotonin is crucial for regulating maturation in the developing brain, and maternal inflammation may result in disruption of the serotonergic system in the perinatal period. Saline or endotoxin was injected intrauterine in pregnant rabbits term. Newborn rabbits underwent positron emission tomography (PET) imaging with α[(11)C]methyl-L-tryptophan (AMT) to evaluate tryptophan metabolism in vivo. Decrease in standard uptake value for AMT and decrease in serotonin concentration was noted in the frontal and parietal cortices of endotoxin kits when compared with controls. In addition, a significant decrease in serotonin-immunoreactive fibers and decreased expression of serotonin transporter (5HTT) was measured in the somatosensory cortex. There was a three-fold increase in the number of apoptotic cells in the ventrobasal (VB) thalamus without loss of raphe serotonergic cell bodies in endotoxin kits when compared with controls. Glutamateric VB neurons projecting to somatosensory cortex transiently express 5HTT and store serotonin, regulating development of the somatosensory cortex. Intrauterine inflammation results in alterations in cortical serotonin and disruption of serotonin-regulated thalamocortical development in the newborn brain. This may be a common link in neurodevelopmental disorders resulting in impairment of the somatosensory system, such as cerebral palsy and autism.
authors.affiliation: Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. skannan@med.wayne.edu
authors.forename: Sujatha
authors.initials: S
authors.lastname: Kannan
authors.forename: Fadoua
authors.initials: F
authors.lastname: Saadani-Makki
authors.forename: Bindu
authors.initials: B
authors.lastname: Balakrishnan
authors.forename: Hui
authors.initials: H
authors.lastname: Dai
authors.forename: Pulak K
authors.initials: PK
authors.lastname: Chakraborty
authors.forename: James
authors.initials: J
authors.lastname: Janisse
authors.forename: Otto
authors.initials: O
authors.lastname: Muzik
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Diane C
authors.initials: DC
authors.lastname: Chugani
mesh_terms: D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008279:Magnetic Resonance Imaging; D009412:Nerve Fibers / Q000187:drug effects / Q000648:ultrastructure; D049268:Positron-Emission Tomography; D011247:Pregnancy; D011817:Rabbits; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis; D013003:Somatosensory Cortex / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D004731:Endotoxins; D050486:Serotonin Plasma Membrane Transport Proteins; C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan; D014365:Tryptophan Hydroxylase
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