In-Utero Neurotoxicity of Nanoparticles

The unique physicochemical properties of nanoparticles (NPs) make them widely used in cosmetics, medicines, food additives, and antibacterial and antiviral compounds. NPs are also used in therapy and diagnostic applications. Depending on their origin, the NPs are commonly classified as naturally occurring and synthetic or anthropogenic NPs. Naturally occurring nanoparticles can be formed by many physical, chemical, and biological processes occurring in all spheres of the earth. However, synthetic NPs are specifically designed or unintentionally produced by different human activities. Owing to their nano size and special properties, the engineered NPs can enter the human body through different routes such as dermal penetration, intravenous injection and inhalation. NPs may accumulate in various tissues and organs including the brain. Indiscriminate use of NP is a matter concern due to the dangers of NP exposure to living organisms. It is possible for NPs to cross the placental barrier, and adversely affect the developing fetus, posing a health hazard in them by causing neurodevelopmental toxicity. Thus, NP-induced neurotoxicity is a topic that demands attention at the maternal-fetal interface. This chapter summarizes the routes by which NPs circumvent the blood-brain barrier, including recent investigations about NPs’ neurotoxicity as well as possible mechanisms involved in neural fetotoxicity.

Insulin-like growth factor reduced against decabromodiphenyl ether-209–induced neurodevelopmental toxicity in vivo and in vitro

Objective How to reduce the neurodevelopmental toxicity of decabromodiphenyl ether (PBDE-209) remains unclear. This study investigated neurodevelopmental toxicity of PBDE-209 and the protective effects of insulin-like growth factor-1 (IGF-1) Methods Pregnant Sprague–Dawley rats were treated with PBDE-209 and IGF-1, and the offspring were subjected to the Morris Water Maze test. Hippocampal neurons were cultured with PBDE-209 and IGF-1 or the PI3K inhibitor or MEK inhibitor for cell viability, apoptosis, immunofluorescence, and Western blot assays. Results Prenatal PBDE-209 exposure impaired the learning and memory ability of rats by delaying the mean latency to the platform compared, whereas prenatal treatment with IGF-1 treatment improved the learning and memory ability. In vitro, treatment of primary cultured hippocampal neural stem cells (H-NSCs) with PBDE-209 reduced cell proliferation and differentiation, but induced apoptosis. In contrast, IGF-1 treatment antagonized the cytotoxic effects of PBDE-209 in H-NSCs in vitro. At the gene level, IGF-1 inhibition of PBDE-209–induced cell cytotoxicity was through the activation of the PI3K/AKT and MEK/ERK signaling pathways in vitro because the effect of IGF-1 was blocked by the AKT inhibitor LY294002 and the ERK1/2 inhibitor PD98059. Conclusion Prenatal PBDE-209 exposure impaired the learning and memory ability of rats, whereas IGF-1 treatment was able to inhibit the neurodevelopmental toxicity of PBDE-209 by activation of the PI3K/AKT and ERK1/2 cell pathways.

Is the Exposome Involved in Brain Disorders through the Serotoninergic System?

Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine acting as a neurotransmitter in the central nervous system (CNS), local mediator in the gut, and vasoactive agent in the blood. It has been linked to a variety of CNS functions and is implicated in many CNS and psychiatric disorders. The high comorbidity between some neuropathies can be partially understood by the fact that these diseases share a common etiology involving the serotoninergic system. In addition to its well-known functions, serotonin has been shown to be a mitogenic factor for a wide range of normal and tumor cells, including glioma cells, in vitro. The developing CNS of fetus and newborn is particularly susceptible to the deleterious effects of neurotoxic substances in our environment, and perinatal exposure could result in the later development of diseases, a hypothesis known as the developmental origin of health and disease. Some of these substances affect the serotoninergic system and could therefore be the source of a silent pandemic of neurodevelopmental toxicity. This review presents the available data that are contributing to the appreciation of the effects of the exposome on the serotoninergic system and their potential link with brain pathologies (neurodevelopmental, neurodegenerative, neurobehavioral disorders, and glioblastoma).

Comparative Milestones in Rodent and Human Postnatal Central Nervous System Development

Within the substantially different time scales characterizing human and rodent brain development, key developmental processes are remarkably preserved. Shared processes include neurogenesis, myelination, synaptogenesis, and neuronal and synaptic pruning. In general, altricial rodents experience greater central nervous system (CNS) immaturity at birth and accelerated postnatal development compared to humans, in which protracted development of certain processes such as neocortical myelination and synaptic maturation extend into adulthood. Within this generalization, differences in developmental rates of various structures must be understood to accurately model human neurodevelopmental toxicity in rodents. Examples include greater postnatal neurogenesis in rodents, particularly within the dentate gyrus of rats, ongoing generation of neurons in the rodent olfactory bulb, differing time lines of neurotransmitter maturation, and differing time lines of cerebellar development. Comparisons are made to the precocial guinea pig and the long-lived naked mole rat, which, like primates, experiences more advanced CNS development at birth, with more protracted postnatal development. Methods to study various developmental processes are summarized using examples of comparative postnatal injury in humans and rodents.

Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring

Background Pregnancy exposure to titanium dioxide nanoparticles (TiO2NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO2NPs on the neurodevelopmental process should be seriously concerned in health risk assessment, especially for the pregnant women who are susceptible to the neurodevelopmental toxicity of nano-sized particles. However, the available evidence of neurodevelopmental toxicity of TiO2NPs remains very limited. Methods In the present study, the pregnant mice were intragastric administered with 150 mg/kg TiO2NPs from gestational day (GD) 8 to 21, the maternal behaviors and neurodevelopment-related indicators in offspring were all assessed at different time points after delivery. The gut microbial community in both dams and their offspring were detected by using 16S ribosomal RNA (rRNA) gene sequencing. The gut-brain axis related indicators were also determined in the offspring. Results The results clearly demonstrated that exposure to TiO2NPs did not affect the maternal behaviors of pregnant mice, or cause the deficits on the developmental milestones and perturbations in the early postnatal development of offspring. Intriguingly, our data revealed that pregnancy exposure of TiO2NPs did not affect locomotor function, learning and memory ability and anxiety-like behavior in offspring at postnatal day (PD) 21, but resulted in obvious impairments on these neurobehaviors at PD49. Similar phenomena were obtained in the composition of gut microbial community, intestinal and brain pathological damage in offspring in adulthood. Moreover, the intestinal dysbiosis induced by TiO2NPs might be highly associated with the delayed appearance of neurobehavioral impairments in offspring, possibly occurring through disruption of gut-brain axis. Conclusions This is the first report elucidated that pregnancy exposure to TiO2NPs caused delayed appearance of neurobehavioral impairments in offspring when they reached adulthood, although these perturbations did not happen at early life after delivery. These findings will provide valuable insights about neurodevelopmental toxicity of TiO2NPs, and call for comprehensive health risk assessment of TiO2NPs on the susceptible population, such as pregnant women. Graphical abstract