Ne, and bromine atoms are represented in black, the residues from the binding pocket. Carbon, nitrogen, oxygen, iodine, and bromine atoms are represented in black, blue, red, blue, red, purple, and magenta, respectively. Single-letter chain identifiers are present next to each and every residue. Hydrophobic purple, and magenta, respectively.curves. Hydrophobic contact prevalent for all ligands are highlighted in bold. contacts are shown as red splines Single-letter chain identifiers are present next to every residue. Hydrophobic contacts are shown as red splines curves. Hydrophobic contact frequent for all ligands are highlighted in bold.7.2. Neurotoxicity Extensive study about PBDE-mediated neurotoxicity around the (creating) nervous system was performed by Dingemans and colleagues [80,84,85]. Animal studies with unique BFR-PBDEs indicated that pre- and postnatal exposure might lead to long-lasting behavioral alterations in particular affecting the motor activity and cognitive behavior. Animal studies in mice revealed that brain improvement is most sensitive to exposure to PBDEs in the initially two weeks right after birth, where the synaptogenesis and myelination take place. As a link to human brain development, it could be concluded that these processes take spot in the final trimester of pregnancy and extend into early childhood [80,868]. Neurochemical alterations have been also observed. Neonatal exposure to BDE-47 (Figure three) (21) was found to impair long-term potentiation in the mouse hippocampus (a kind of synaptic plasticity linked with memory) [89]. Related findings were observed in rat dentate gyrus in vivo when exposed to the totally brominated BDE-209/Deca-BDE (Figure three) (20) throughout diverse developmental stages [90]. Another BFR-PBDE, BDE-99 (29), enhanced the activity with the glutamate-nitric-oxide-cyclin guanosine monophosphate pathway in the rat cerebellum [91]. Summarizing, the effects of BFR-PBDEs on the brain had been observed within the hippocampus, cortex, striatum, and cerebellum. Alterations of protein levels PKCĪµ Molecular Weight involved in synapticMolecules 2021, 26,11 ofplasticity and brain improvement were also detected (reviewed in [80]). These effects were seen upon remedy with tetra- and penta-BDEs or octa- through deca-BDEs [80]. Referring to cell viability, several in vitro studies showed tetra- and penta-BDEs to induce apoptosis in major neurons or neuronal cell lines, which was assumed to outcome from oxidative tension [926]. Apart from effects on cell viability, also cell differentiation, migration, and neuronal signaling were impaired upon PBDE exposure in several Mitochondrial Metabolism Molecular Weight research (reviewed in [80]). Taken with each other, it was postulated that tetra- or penta-brominated PBDEs impact all levels of neurotransmission, for instance compromising the presynaptic neurotransmitter homeostasis up to their release to postsynaptic receptors. Though OH-PBDEs possess a larger potency than their parent congeners, the primary molecular target of (OH-)PBDEs remains elusive [80]. 7.three. Other Effects Upon exposure to BDE-209/Deca-BDE (Figure 3) (20), an increased incidence of hepatocellular carcinomas and thyroid adenomas has been observed in rodents. Also, prenatal exposure to BDE-99 (29) was identified to reduce sperm counts in adult rats. As a result, PBDEs also influence the reproductive capacity. Furthermore, some tetra-BDEs and OHtetra-BDEs caused genotoxicity by DNA harm through reactive oxygen species (ROS), leading to replication blockage and subsequent chromosomal breaks in chicken DT40 cell lines [97]. Some BF.