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 a[ 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.

Neonatal Systemic Inflammation Induces Inflammatory Reactions and Brain Apoptosis in a Pathogen-Specific Manner

“…Researchers have approached a sepsis-like scenario by using LPS in various animal models spanning a wide range of clinical fields [29,30]. LPS is relatively inexpensive and has been thoroughly investigated as a potent inflammatory trigger.…”

Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology

“…112 These results are somewhat in line with those of a PET study in rabbits using a similar imaging methodology, suggesting lower 5-HT synthesis in the frontal cortex in animals exposed to endotoxin in utero relative to controls. 113 Given that the 5-HT system develops and matures rapidly for a large part, these findings may suggest that the impact of certain stressors on 5-HT synthesis in the limbic pathways may be most pronounced at the time that the 5-HT system undergoes the most developmental changes.…”

Models of Fetal Brain Injury, Intrauterine Inflammation, and Preterm Birth

“…Impaired development of the sensory cortex and decreased serotonin are seen in patients with ASD. 44,[55][56][57] These studies indicate that ongoing activation of microglial cells may be responsible for the development of white matter and neuronal injury in infants exposed to intrauterine infections/inflammation (Fig. 2).…”