Perinatal exposure to metal mixtures disrupts neuronal function and behavior

作者：Naveen Chandra, Benyamin Karimi, Ankita Bhobe, Susmitha R. Pagadala, Shekhar Pandey, Sylvia Sanchez, Bonnie Yeung‐Luk, Emily Rivera, Mark J. Kohr, Beth Riess, Keeve E. Nachman, Shyam Biswal, Fenna C.M. Sillé, Austin R. Graves · 发表于：Environmental Research · 年份：2026 · DOI：10.1016/j.envres.2026.123803 · 被引用次数：3 · 研究领域：Heavy Metal Exposure and Toxicity、Aluminum toxicity and tolerance in plants and animals、Trace Elements in Health

BACKGROUND: Environmental exposure to heavy metals such as lead (Pb), arsenic (As), hexavalent chromium [Cr(VI)], and cadmium (Cd), (PACC), is linked to neurodevelopmental disorders. These metals often co-occur in contaminated environments, but their combined effects on brain development remain poorly understood. OBJECTIVE: To test the hypothesis that perinatal exposure to a mixture of environmentally relevant levels of Pb, As, Cd, and Cr(VI), causes developmental defects in cognition, behavior, and neuronal function. METHODS: Female C57BL/6J mice were exposed to either a single metal or the PACC mixture in drinking water. Exposure began two weeks preconception and continued until weaning at postnatal day 21. Juvenile mice were tested at 4-5 weeks of age in open field (locomotion), novel object recognition (short-term memory), Y-maze (working memory), and elevated plus maze (anxiety-like behavior). A subset of animals underwent Whole-cell patch-clamp recordings in the medial prefrontal cortex (mPFC) and hippocampal CA1 neurons. RESULTS: Perinatal exposure to PACC metal mixture increased anxiety-like behavior and impaired short-term memory but not locomotion or working memory. Pyramidal neurons in mPFC and hippocampal CA1 displayed increased intrinsic excitability, mPFC neurons also showed elevated amplitude in spontaneous excitatory postsynaptic currents. DISCUSSION: Our findings suggest that perinatal exposure to the PACC metal mixture impairs cognition, increases anxiety-li...