Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 161, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2022.112831
Keywords
Lanthanum; Hippocampus; Autophagy; Mitochondrial-associated membranes; ROS
Categories
Funding
- National Natural Science Foundation of China [81773469, 81373024]
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Lanthanum has been shown to have neurotoxicity that impairs learning and memory ability. However, the mechanisms underlying its neurotoxicity are not fully understood. Autophagy is a process that degrades damaged organelles and macromolecules, and it may play a role in the effects of lanthanum on the nervous system.
Lanthanum is one of REEs documented to have neurotoxicity that led to learning and memory ability impairments. However, the mechanisms underlying La-induced neurotoxicity remain largely unexplored. Autophagy is a self-balancing and self-renewal process that degrades damaged organelles and macromolecules through lysosomal pathway. Importantly, appropriate autophagy levels have protective effects against harmful stress, while excessive autophagy has been demonstrated to be implicated in neurological diseases. ER is close to mitochondria at specific sites with a reported distance of 10-30 nm. The functional domains between the two organelles, called MAM, have been associated with autophagosome synthesis. In this study, the pregnant Wistar rats were randomly divided into four groups and given distilled water solution containing 0%, 0.125%, 0.25%, and 0.5% LaCl3 for drinking during gestation and lactation. The pups were exposed to LaCl3 via the maternal placenta and three-week lactation. Experimental results showed that LaCl3 decreased spatial learning and memory ability of offspring rats, decreased tethering protein complexes expression of MAM, damaged MAM structure, up-regulated NOX4 expression which led to active ROS-AMPK-mTOR signaling pathway. Our findings suggest that decreased spatial learning and memory ability induced by LaCl3 may be related to the abnormally autophagy regulated by tethering protein complexes of MAM.
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