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pmid:36518382

A proteomic study to unveil lead toxicity-induced memory impairments invoked by synaptic dysregulation.

Nivedha Mohanraj · Neha S Joshi · Roshni Poulose · Rahul R Patil · Rashmi Santhoshkumar · Anubhav Kumar · Girish P Waghmare · Amit Kumar Saha · Syeda Zehra Haider · Yogananda S Markandeya · Gourav Dey · Laxmi T Rao · Periyasamy Govindaraj · Bhupesh Mehta

Toxicology reports · 2022 doi:10.1016/j.toxrep.2022.07.002

Paper

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Experiment

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Data

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A proteomic study to unveil lead toxicity-induced memory impairments invoked by synaptic dysregulation.
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10.1016/j.toxrep.2022.07.002
pmid
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Nivedha Mohanraj
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Neha S Joshi
[2]
Roshni Poulose
[3]
Rahul R Patil
[4]
Rashmi Santhoshkumar
[5]
Anubhav Kumar
[6]
Girish P Waghmare
[7]
Amit Kumar Saha
[8]
Syeda Zehra Haider
[9]
Yogananda S Markandeya
[10]
Gourav Dey
[11]
Laxmi T Rao
[12]
Periyasamy Govindaraj
[13]
Bhupesh Mehta
journal
Toxicology reports
year
2022
abstract
Lead (Pb2+), a ubiquitously present heavy metal toxin, has various detrimental effects on memory and cognition. However, the molecular processes affected by Pb2+ causing structural and functional anomalies are still unclear. To explore this, we employed behavioral and proteomic approaches using rat pups exposed to lead acetate through maternal lactation from postnatal day 0 (P0) until weaning. Behavioral results from three-month-old rats clearly emphasized the early life Pb2+ exposure induced impairments in spatial cognition. Further, proteomic analysis of synaptosomal fractions revealed differential alteration of 289 proteins, which shows functional significance in elucidating Pb2+ induced physiological changes. Focusing on the association of Small Ubiquitin-like MOdifier (SUMO), a post-translational modification, with Pb2+ induced cognitive abnormalities, we identified 45 key SUMO target proteins. The significant downregulation of SUMO target proteins such as metabotropic glutamate receptor 3 (GRM3), glutamate receptor isoforms 2 and 3 (GRIA 2 and GRIA3) and flotilin-1 (FLOT1) indicates SUMOylation at the synapses could contribute to and drive Pb2+ induced physiological imbalance. These findings identify SUMOylation as a vital protein modifier with potential roles in hippocampal memory consolidation and regulation of cognition. Data availbility: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034212&#34.
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