IMPACT OF ANXIOLYTIC TREATMENT ON NEURAL DEVELOPMENT: FIRST EVIDENCE ON XENOPUS LAEVIS EMBRYOS

Anxiolytics, such as benzodiazepine, are prescribed to pregnant women for acute and ongoing treatment. These medications can cross the placental barrier, potentially affecting fetal and brain development. Exposure to these drugs during pregnancy might disrupt neurotransmitter systems in the brain, leading to enduring effects on the offspring’s neurodevelopment1. Delorazepam is a benzodiazepine which binds to the GABA-A receptor, enhancing the activity of the GABA neurotransmitter, which, in early embryogenesis, acts as a developmental signal involved in regulating cell migration, axonal outgrowth, and synaptogenesis, and as a coordinating mediator of intercellular communication in the fetus2. Higher levels of GABA, resulting from prenatal exposure to anxiolytics, could potentially lead to changes in brain structure and function. In this preliminary study, a modified version of FETAX3 test was employed by exposing Xenopus laevis embryos, from stage 4-8 cells to three increasing doses of delorazepam: the aim was to understand if and how treatment with these common drugs can reshape neural growth during early embryonic development. Using optical and electronic microscopy techniques, morphometric tests and gene expression of the main markers of brain function and development (BDNF, GAPDH, otx2, sox3) important variations were highlighted starting from the minimum dose administered. Considering that major signaling pathways in brain patterning are highly conserved between frogs and mammals4, the results raise alarm bells on the possible risk of neurodevelopment problems following exposure to anxiolytics in the early stages of embryonic development.