Salmeron, A. | bioRxiv Science

bioRxiv2024

Modulating Neurotoxic Effects of Prenatal Chlorpyrifos Exposure Through Probiotic and Vitamin D Gestational Supplementation: Unexpected Effects on Neurodevelopment and Sociability

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.

neuroscience↗

bioRxiv2023

Spatial and temporal characterization of the rich fraction of plastid DNA present in the nuclear genome of Moringa oleifera reveals unanticipated complexity in NUPTs' formation

Beyond the massive amounts of DNA and genes transferred from the protoorganelle genome to the nucleus during the endosymbiotic event that gave rise to the plastids, stretches of plastid DNA of varying size are still being copied and relocated to the nuclear genome in a process that is ongoing and does not result in the concomitant shrinking of the plastid genome. As a result, plant nuclear genomes are featured by a small, but variable, fraction of their genomes of plastid origin, the so-called nuclear plastid DNA sequences (NUPTs). However, research on the topic was mostly focused on a limited number of species and of plastid DNA. Here, we leveraged a chromosome-scale version of the Moringa oleifera genome, featured by the largest fraction of plastid DNA in any plant nuclear genome, to examine the chromosomal distribution and arrangement of NUPTs, to explicitly model and test the correlation between their age and size distribution, as well as to characterize their sites of origin at the chloroplast genome and their sites of insertion at the nuclear one. We found a bimodal distribution of NUPT relative ages, which implies NUPTs in moringa were formed through two separate events. Furthermore, NUPTs from every event showed markedly distinctive features, suggesting they originated through distinct mechanisms. Our results reveal an unanticipated complexity of the mechanisms at the origin of NUPTs and of the evolutionary forces behind their fixation and highlight moringa species as an exceptional model to study the mechanisms of origin and evolutionary fate of NUPTs. Significance statementSequencing of plant genomes has revealed the presence of a variable, but significant, content of DNA arising from their organelles, i.e., plastids and mitochondria. However, the mechanisms underlying their origin and fixation are not yet fully elucidated. Here, by thoroughly examining the spatial and temporal distribution of the large fraction of plastid DNA present in the nuclear genome of the orphan crop Moringa oleifera, we identified their episodic origin trough seemingly distinct mechanisms, highlighting the complexity of the molecular and evolutionary dynamics underlying their origin and fixation and revealing moringa as an outstanding model to assess the impact of plastid DNA in the evolution of the architecture and function of plant nuclear genomes.

genomics↗