Tamagno and Freeman 2025 — Glutamate-Mediated Neural Alterations in Lead Exposure
Summary
This is a 2025 peer-reviewed mechanistic review by Wagner A. Tamagno and Jennifer L. Freeman (Purdue University, School of Health Sciences) on the molecular pathways through which lead disrupts glutamatergic signaling in the central nervous system, with emphasis on mechanisms relevant to childhood developmental neurotoxicity. The review covers Pb interference with ionotropic glutamate receptors (NMDA and AMPA), metabotropic receptors, glutamate transporters (EAATs, VGLUTs, SNATs), and metabolic pathways (glutamate-glutamine cycle, TCA cycle, glutathione synthesis). The mechanistic core is Pb²⁺ mimicry of divalent cations Ca²⁺ and Zn²⁺, which disrupts calcium homeostasis, exacerbates excitotoxicity, and induces oxidative stress, ultimately impairing neuronal communication and synaptic function. The review is the type of mechanistic source that complements the dose-response regulatory frame from EFSA 2010 and provides the molecular-level explanation for the developmental neurotoxicity endpoint that drives every modern lead reference value.
Provenance notes
License public-reference-only. The filename Biochem_Lead_Amin_2025.pdf is misleading: the actual authors are Tamagno (W.A.) and Freeman (J.L.); “Amin” does not appear as an author. Cite key uses the actual authorship, not the filename. Journal of publication and DOI require verification from the full-text article; the extracted abstract and front matter do not include the journal title in machine-readable form.