Arsenic induces autophagy in developmental mouse cerebral cortex and hippocampus by inhibiting PI3K/Akt/mTOR signaling pathway: involvement of blood-brain barrier's tight junction proteins.

Arsenic induces autophagy in developmental mouse cerebral cortex and hippocampus by inhibiting PI3K/Akt/mTOR signaling pathway: involvement of blood-brain barrier's tight junction proteins.
Arch Toxicol. 2018 Sep 17;:
Authors: Manthari RK, Tikka C, Ommati MM, Niu R, Sun Z, Wang J, Zhang J, Wang J
Abstract
For the past decade, there has been an increased concern about the health risks from arsenic (As) exposure, because of its neurotoxic effects on the developing brain. The exact mechanism underlying As-induced neurotoxicity during sensitive periods of brain development remains unclear, especially the role of blood-brain barrier's (BBB) tight junction (TJ) proteins during As-induced neurotoxicity. Here, we highlight the involvement of TJ proteins in As-induced autophagy in cerebral cortex and hippocampus during developmental periods [postnatal day (PND) 21, 28, 35 and 42]. Here, the administration of arsenic trioxide (As2O3) at doses of 0.15 mg or 1.5 mg or 15 mg As2O3/L in drinking water from gestational to lactational and continued to the pups till PND42 resulted in a significant decrease in the mRNA expression levels of TJ proteins (Occludin, Claudin, ZO-1 and ZO-2) and Occludin protein expression level. In addition, As exposure significantly decreased PI3K, Akt, mTOR, and p62 with a concomitant increase in Beclin1, LC3I, LC3II, Atg5 and Atg12. Moreover, As exposure also significantly downregulated the protein expression levels ...

Source: Archives of Toxicology - September 17, 2018 Category: Toxicology Authors: Manthari RK, Tikka C, Ommati MM, Niu R, Sun Z, Wang J, Zhang J, Wang J Tags: Arch Toxicol Source Type: research