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Neonatal hyperbilirubinemia may result in long-lasting motor, auditory and learning impairments. The mechanisms responsible for the localization of unconjugated bilirubin (UCB) to specific brain areas as well as those involved in potentially permanent central nervous system (CNS) dysfunctions are far from being clear. One area of investigation includes exploring how hyperbilirubinemia determines neuronal alterations predisposing to neurodevelopmental disorders. We focused on the hippocampus and pyramidal cell dysregulation of calcium homeostasis and synaptic activity, with a particular focus on early forms of correlated network activity, i.e., giant depolarizing potentials (GDPs), crucially involved in shaping mature synaptic networks. We performed live calcium imaging and patch clamp recordings from acute hippocampal slices isolated from wild-type rats exposed to exogenous high bilirubin concentration. We then explored the impact of endogenous bilirubin accumulation in hippocampal slices isolated from a genetic model of hyperbilirubinemia, i.e., Gunn rats. Our data show in both models an age-dependent dysregulation of calcium dynamics accompanied by severe alterations in GDPs, which were strongly reduced in hippocampal slices of hyperbilirubinemic rats, where the expression of GABAergic neurotransmission markers was also altered. We propose that hyperbilirubinemia damages neurons and affects the refinement of GABAergic synaptic circuitry during a critical period of hippocampal development.

The reducing power of iodide anion is an underexplored property that can be used for the cross-electrophile coupling of organic molecules. Herein we harness this trait for the preparation of tertiary amines through the combination of two simple reagents: an electrophilic-carbon precursor and an iminium iodide in a dual role - both as nitrogen-containing building block and as reducing agent. The underlying mechanism of this new C-C bond-formation paradigm is explored through a combination of experiment and quantum chemical calculations., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)