Fernando Sánchez-Santed

Air pollution has been increasingly linked to adverse neurodevelopmental and neurodegenerative outcomes. While experimental and preclinical studies suggest that exposure to particulate matter (PM), particularly during gestation, may disrupt cognitive development, the impact of short-term PM exposure on cognitive and behavioral functioning in healthy young populations remains insufficiently explored in Spain. Moreover, few studies have incorporated individualized dosimetry models to estimate exposure more accurately. This study included 186 healthy young adults (mean age = 20.4 years) recruited from three Spanish cities (Teruel, Almería, and Talavera) characterized by different pollution levels. Ambient fine and coarse PM concentrations were recorded 8, 15, and 30 days prior to psychological assessment. Instead of relying solely on raw in situ environmental measurements, individualized PM deposition was estimated using the Multiple-Path Particle Dosimetry Model (MPPD), allowing a more biologically meaningful exposure approximation. Psychological outcomes were assessed using validated questionnaires: DASS-21 (depression, anxiety, stress), BIS-11 (impulsivity), UCLA Loneliness Scale, and SWLS (life satisfaction). Behavioral performance was evaluated using computerized versions of the Attentional Network Task (ANT) and the Stroop Task. Blood NRF2 concentrations were analyzed as a biomarker potentially related to oxidative stress mechanisms. In situ data indicated that Talavera presented the highest pollution levels, followed by Almería and Teruel. Linear regression analyses showed that coarse PM exposure across 8-, 15-, and 30-day windows significantly predicted poorer Executive Control Index performance in the ANT. Additionally, 15-day coarse PM and 30-day fine PM exposure were associated with greater cognitive interference. Oxidative stress markers were significantly associated with PM exposure levels. These findings support emerging evidence that short-term PM exposure may negatively affect executive and attentional processes even in healthy young adults. Further longitudinal research incorporating individualized exposure modeling is warranted to clarify causal pathways and underlying biological mechanisms. Graphical

Pesticides are essential for modern agriculture but raise concerns about potential neurodevelopmental consequences, leading to bans in some countries. This study aimed to investigate the long-term effects of prenatal exposure to chlorpyrifos (CPF) on behavior and DNA methylation, considering genetic susceptibility via the apolipoprotein E (APOE) genotype. Pregnant mice—C57BL/6J and those carrying human APOE ε3 or ε4 alleles—were orally exposed to 0 or 1 mg/kg/day of CPF from gestational day 12 to 18. Adult offspring underwent light and dark and Morris water maze tests to assess anxiety-like behavior and spatial learning and memory. Then, hippocampal samples were collected to assess DNA methylation. Results indicated that body weight was lower in females and CPF-treated mice. C57BL/6J males spent less time in the light compartment, worsened by CPF. In contrast, within APOE genotype ε4 carriers spent more time in the light compartment, with CPF increasing male activity. Moreover, long-term retention was impaired in both male and female apoE4 mice prenatally exposed to CPF. DNA methylation analysis revealed sex-dependent differences, with hypomethylation in the CPF-treated male hippocampus. These findings highlight how pesticides and genetic factors interact, affecting neurobehavioral development, and explore the potential impact of CPF on DNA methylation.

Gut-brain axis and probiotics supplementation during gestational period have gained an especial attention in the field of neurodevelopmental disorders. However, the influence of prenatal probiotics in physiology and neurodevelopment of healthy organisms is widely unexplored and probiotics are commercially such as dietetic supplementations without the necessity of ensuring safety in healthy organisms, as is required for drugs. The aim is to present and discuss the various biochemical, developmental and behavioral effects that prenatal probiotics have on the offspring of healthy organisms in rodent models and assess their security during gestation. We included a total of 15 preclinical studies discarding all those that did not have an appropriate control for the probiotic-treated group. Results suggest that probiotics, particularly Lactobacillus strains, influenced anxiety-like behaviors in mice and GABAergic system maturation, showing an apparent biphasic effect, reducing GABA functioning in early life but increasing them in later stages; and both prenatal Lactobacillus and Bifidobacterium , influenced microbiota and general development of healthy organisms. However, the significant variations in methodologies used across studies complicate the ability to elucidate specific conclusions related to bacterial strains or doses. Further research is imperative to ensure the safety and regulation of probiotic interventions, particularly during the gestational period.

Autism is a neurodevelopmental disorder characterized by impairments in sociability and communication. Prenatal exposure to Chlorpyrifos has been associated with autism-like behaviors in preclinical models. Interest has grown in the gut-brain axis and the role of microbiota modulation through dietetic supplementation to reduce this ASD-like phenotype. This study examines the effects of prenatal CPF exposure in Wistar Rats and assesses the potential of gestational probiotic and vitamin D supplementation to mitigate these effects in offspring. CPF exposure significantly impaired sociability in adolescence, and supplementation did not reverse these deficits. However, in control animals, supplementation induced neurodevelopmental changes, including alterations in metabolic status, the pattern of expression of ASD-related genes, the regulation of oxytocin and vasopressin receptors, and the GABAergic system in the brain. Additionally, supplementation accelerated overall development, increased ultrasonic vocalization emission and modified the typical responses to social novelty. CPF exposure blocked most of these effects at both behavioral and molecular levels. While supplementation did not block CPF-induced impairments, CPF exposure altered the observed effects of supplementation in controls, possibly indicating shared molecular mechanisms. These findings highlight the need for further research into the safety of probiotic and vitamin D supplementation during pregnancy.

In recent years, exposures to organophosphate pesticide have been highlighted as a possible cause or aggravating factor of autism spectrum disorder (ASD). The present study examined if Wistar rats prenatally exposed to chlorpyrifos (CPF) at a dose of 1 mg/kg in GD 12.5–15.5 could express similar behaviors to those exposed to valproic acid (VPA, 400 mg/kg) during the same administration window, which is an accepted animal model of autism. The 3-chambered test was employed to evaluate sociability and reaction to social novelty in two experiments, the first in adolescence and the second in adulthood. The results obtained in this study show that animals prenatally treated with CPF or VPA show a similar behavioral phenotype compared to the control group (CNT). In adolescence, the CPF animals showed a negative index in the reaction to social novelty, followed closely by the VPA, while both experimental groups showed a recovery in this aspect during adulthood. This study therefore provides evidence to suggest that prenatal exposure to CPF in rats could have similar effects on certain components of sociability to those seen in autistic models.