Intra-Amniotic LPS Induced Region-Specific Changes in Presynaptic Bouton Densities in the Ovine Fetal Brain

Abstract

Rationale. Chorioamnionitis has been associated with increased risk for fetal brain damage. Although, it is now accepted that synaptic dysfunction might be responsible for functional deficits, synaptic densities/numbers after a fetal inflammatory challenge have not been studied in different regions yet. Therefore, we tested in this study the hypothesis that LPS-induced chorioamnionitis caused profound changes in synaptic densities in different regions of the fetal sheep brain. Material and Methods. Chorioamnionitis was induced by a 10 mg intra-amniotic LPS injection at two different exposure intervals. The fetal brain was studied at 125 days of gestation (term = 150 days) either 2 (LPS2D group) or 14 days (LPS14D group) after LPS or saline injection (control group). Synaptophysin immunohistochemistry was used to quantify the presynaptic density in layers 2-3 and 5-6 of the motor cortex, somatosensory cortex, entorhinal cortex, and piriforme cortex, in the nucleus caudatus and putamen and in CA1/2, CA3, and dentate gyrus of the hippocampus. Results. There was a significant reduction in presynaptic bouton densities in layers 2-3 and 5-6 of the motor cortex and in layers 2-3 of the entorhinal and the somatosensory cortex, in the nucleus caudate and putamen and the CA1/2 and CA3 of the hippocampus in the LPS2D compared to control animals. Only in the motor cortex and putamen, the presynaptic density was significantly decreased in the LPS14 D compared to the control group. No changes were found in the dentate gyrus of the hippocampus and the piriforme cortex. Conclusion. We demonstrated that LPS-induced chorioamnionitis caused a decreased density in presynaptic boutons in different areas in the fetal brain. These synaptic changes seemed to be region-specific, with some regions being more affected than others, and seemed to be transient in some regions.

Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups

“…As IUGR neurodevelopment is thought to be delayed due to reduced nutrients during a critical phase of cerebral development (26–28), the present result suggest that IUGR leads to transient delay in synaptogenesis in the cortex in P7 restricted rats. Similarly in sheep (29), impaired fetal environment was induced by an intra-amniotic lipopolysaccharide pro-inflammatory environment and cerebral synaptophysin expression was reported to be decreased in motor, somatosensory and entorhinal cortices causing reduction in density of presynaptical boutons.…”

Differential Brain and Cerebrospinal Fluid Proteomic Responses to Acute Prenatal Endotoxin Exposure

“…CA is associated with 40-70% of preterm births (Jain et al, 2021) and leads to cerebral lesions and neurodevelopmental delay (Adams-Chapman & Stoll, 2006); however, the links are not clear and may depend on the time, duration and type of perinatal in ammation. CA may induce lesions in white matter, such as altered vascular microstructure and periventricular hemorrhage, as well as lesions in grey matter, such as increased neuronal apoptosis, abnormal neuronal circuit formation and cognitive impairments (Versland et al, 2006;Nasef et al, 2013;Strackx et al, 2015;Anblagan et al, 2016). Recent data also suggested that neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia, might have a neurodevelopmental origin and be linked to feto-maternal in ammation (Pinelli & Zwaigenbaum, 2008;Hagberg et al, 2015;Estes & McAllister, 2016;Thorell et al, 2020).…”

“…Recent data also suggested that neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia, might have a neurodevelopmental origin and be linked to feto-maternal in ammation (Pinelli & Zwaigenbaum, 2008;Hagberg et al, 2015;Estes & McAllister, 2016;Thorell et al, 2020). CA-related brain lesions may be mediated in spatiotemporal ways by several mechanisms, including transport of cytotoxic molecules across the blood-brain barrier (BBB), transient activation of microglia accompanied by release of proin ammatory cytokines and reactive oxygen species, arrest of preoligodendrocyte maturation followed by hypomyelination, reduced synaptic density, impaired neurogenesis and cell death (Burd et al, 2012;Back & Rosenberg, 2014;Strackx et al, 2015;Penn et al, 2016;Gussenhoven et al, 2018). In particular, the hippocampus, a brain region centrally involved in memory and cognitive processes, was shown to be affected in various preclinical models of CA (Gavilanes et al, 2009;Gussenhoven et al, 2018), and it has a smaller volume in preterm infants exposed to CA (Hat eld et al, 2011).…”

Differential Brain and Cerebrospinal Fluid Proteomic Responses To Acute Prenatal Endotoxin Exposure

“…CA is associated with 40-70% of preterm births (Jain et al, 2021) and leads to cerebral lesions and neurodevelopmental delay (Adams-Chapman & Stoll, 2006); however, the links are not clear and may depend on the time, duration and type of perinatal in ammation. CA may induce lesions in white matter, such as altered vascular microstructure and periventricular hemorrhage, as well as lesions in grey matter, such as increased neuronal apoptosis, abnormal neuronal circuit formation and cognitive impairments (Versland et al, 2006;Nasef et al, 2013;Strackx et al, 2015;Anblagan et al, 2016). Recent data also suggested that neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia, might have a neurodevelopmental origin and be linked to feto-maternal in ammation (Pinelli & Zwaigenbaum, 2008;Hagberg et al, 2015;Estes & McAllister, 2016;Thorell et al, 2020).…”