AMIGO2, or amphoterin-induced gene and ORF (open reading frame) 2, belongs to the leucine-rich repeats and immunoglobulin superfamilies. The protein is a downstream target of calcium-dependent survival signals and, therefore, promotes neuronal survival. Here, we describe the mRNA distribution pattern of AMIGO2 throughout the mouse brain with special emphasis on the hippocampus. In the Ammon's horn, a detailed comparison between the subregional mRNA expression patterns of AMIGO2 and Pcp4 (Purkinje cell protein 4)--a known molecular marker of hippocampal CA2 (Cornu Ammonis 2)--revealed a prominent AMIGO2 mRNA expression level in both the CA2 and the CA3a (Cornu Ammonis 3a) subregion of the dorsal and ventral hippocampus. Since this CA2/CA3a region is particularly resistant to neuronal injury and neurotoxicity [Stanfield and Cowan (Brain Res 309(2):299–307 1984); Sloviter (J Comp Neurol 280(2):183–196 1989); Leranth and Ribak (Exp Brain Res 85(1):129–136 1991); Young and Dragunow (Exp Neurol 133(2):125–137 1995); Ochiishi et al. (Neurosci 93(3):955–967 1999)], we suggest that the expression pattern of AMIGO2 indeed fits with its involvement in neuroprotection.

Thymosin beta 4 (Tbeta4) is a peptide of 43 amino acids, mainly recognized as a regulator of actin polymerization by sequestering G-actin. Meanwhile, the peptide has been implicated in lymphocyte maturation, carcinogenesis, apoptosis, angiogenesis, blood coagulation and wound healing. The peptide is also involved in lesion-induced neuroplasticity through microglia upregulation and it participates in the growth of neuronal processes. However, its precise cellular localization throughout the entire body of the mouse has not been documented. We therefore initiated a detailed investigation of the tissue distribution and cellular expression of the Tbeta4 peptide and its precursor mRNA by immunocytochemistry and in situ hybridization, respectively. In the brain, Tbeta4 was clearly present in neurons of the olfactory bulb, neocortex, hippocampus, striatum, amygdala, piriform cortex and cerebellum, and in microglia across the entire brain. We further localized Tbeta4 in cells, typically with many processes, inside thymus, spleen, lung, kidney, liver, adrenal gland, stomach and intestine. Remarkably, Tbeta4 was thus associated with microglia and macrophages, the differentiated phagocytic cells residing in every tissue. Motility and phagocytosis, two important activities of macrophages, depend on actin, which can explain the presence of Tbeta4 in these cells.

The expression patterns of the medium- and high-molecular-weight subunits of the neurofilament protein triplet have been extensively studied in several neuroanatomical studies. In the present study, we report the use of the low-molecular-weight neurofilament protein subunit (NF-L) as a reliable marker within the neurofilament protein family to reveal the regional architecture of mammalian neocortex. We document clearly its usefulness in anatomical parcellation studies and report unique expression patterns of NF-L throughout the mouse neocortex. NF-L was most abundant in the somatosensory cortex, the lateral secondary visual area, the granular insular cortex, and the motor cortex. Low NF-L staining intensity was observed in the agranular insular cortex, the prelimbic and infralimbic cortex, the anterior cingulate cortex, the visual rostromedial areas, the temporal association cortex, the ectorhinal cortex, and the lateral entorhinal cortex. NF-L immunoreactivity was present in the perikarya, dendrites, and proximal segment of axons primarily of pyramidal neurons, and was mainly located in layers II and III, and to a lesser extent in layers V and VI. Interestingly, Black-Gold myelin staining confirmed a close correlation between NF-L immunoreactivity and myelination patterns. The characteristic and distinctive distribution and laminar expression profiles of NF-L make it an excellent tool to assess accurately topographical boundaries among neocortical areas as illustrated herein in the adult mouse brain.

There is increasing epidemiologic evidence that arsenic exposure in utero is associated with adverse pregnancy outcomes and may contribute to long-term health effects. These effects may occur at low environmental exposures but the underlying molecular mechanism is not clear. We collected cord blood samples of 183 newborns to identify associations between arsenic levels and birth anthropometric parameters in an area with very low arsenic exposure. Our core research aim was to screen for transcriptional marks that mechanistically explain these associations. Multiple regression analyses showed that birth weight decreased with 47 g (95% CI: 16–78 g) for an interquartile range increase of 0.99 μg/L arsenic. The model was adjusted for child’s sex, maternal smoking during pregnancy, gestational age, and parity. Higher arsenic concentrations and reduced birth weight were positively associated with changes in expression of the sFLT1 (soluble fms-like tyrosine kinase-1) gene in cord blood cells in girls. The protein product of sFLT1 is a scavenger of vascular endothelial growth factor (VEGF) in the extracellular environment and plays a key role in the inhibition of placental angiogenesis. In terms of fetal development, inhibition of placental angiogenesis leads to impaired nutrition and hence to growth retardation. Various genes related to DNA methylation and oxidative stress showed also changed expression in relation to arsenic exposure but were not related to birth outcome parameters. In conclusion, this study suggests that increased expression of sFLT1 is an intermediate marker that points to placental angiogenesis as a pathway linking prenatal arsenic exposure to reduced birth weight.

Personal care products (PCPs), such as soaps, perfumes, cosmetics, lotions, etc., contain a variety of chemicals that have been described as potentially hormone disrupting chemicals. Therefore, it is important to assess the internal exposure of these chemicals in humans. Within the 2nd Flemish Environment and Health Study (FLEHS II, 2007-2011), the human exposure to three classes of pollutants that are present in a wide variety of PCPs--i.e. polycyclic musks (galaxolide, HHCB and tonalide, AHTN in blood), parabens (urinary para-hydroxybenzoic acid, HBA) and triclosan (urinary TCS)--was assessed in 210 Flemish adolescents (14-15 years) and in 204 adults (20-40 years) randomly selected from the general population according to a stratified two stage clustered study design. The aim of this study was to define average levels of exposure in the general Flemish population and to identify determinants of exposure. Average levels (GM (95% CI)) in the Flemish adolescents were 0.717 (0.682-0.753) μg/L for blood HHCB; 0.118 (0.108-0.128) μg/L for blood AHTN; 1022 (723-1436) μg/L for urinary HBA and 2.19 (1.64-2.92) μg/L for urinary TCS. In the adults, levels of HBA were on average 634 (471-970) μg/L. Inter-individual variability was small for HHCB and AHTN, intermediate for HBA, and large for TCS. All biomarkers were positively associated with the use of PCPs. Additionally, levels of HHCB and AHTN increased with higher educational level of the adolescents. Both in adults and adolescents, urinary HBA levels were negatively correlated with BMI. We define here Flemish exposure values for biomarkers of PCPs, which can serve as baseline exposure levels to identify exposure trends in future biomonitoring campaigns.