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Title: Null allele mutants of trt-1, the catalytic subunit of telomerase in Caenorhabditis elegans, are less sensitive to Mn-induced toxicity and DAergic degeneration.

Authors: Ijomone, Omamuyovwi M; Miah, Mahfuzur R; Peres, Tanara V; Nwoha, Polycarp U; Aschner, Michael

Published In Neurotoxicology, (2016 Dec)

Abstract: Exposure to manganese (Mn) represents an environmental risk factor for Parkinson's disease (PD). Recent evidence suggests that telomerase reverse transcriptase (TERT), the catalytic subunit of mammalian telomerase participates in non-telomeric functions and may play a role in cellular protection from oxidative stress and DNA damage. trt-1 is the catalytic subunit of telomerase in Caenorhabditis elegans (C. elegans). The present study investigated the relationship between trt-1 mutation and Mn-induced neurotoxicity. Wild-type (wt) and trt-1 worms were subjected to an acute Mn treatment of 1h at the first larval (L1) stage. Survival assay and behavior (Basal slowing response, chemotaxis) were assessed. Dopaminergic (DAergic) neurodegeneration was evaluated in successful crosses of trt-1 worms expressing green fluorescent protein (GFP) (dat-1:GFP worms). trt-1 worms were less sensitive to Mn-induced lethality compared to wt worms. Mn induced DAergic degeneration in wt worms, but not in trt-1 worms. Basal slowing was altered in both wt and trt-1 worms; however trt-1 worms were significantly less affected in their basal slowing behavior compared to wt worms. Mn treatment did not affect chemotaxis by NaCl in either wt or trt-1 mutants worms. Combined, the results establish that null mutation in trt-1 improves survival and attenuates damage to the DAergic system.

PubMed ID: 27593554 Exiting the NIEHS site

MeSH Terms: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Chlorides/toxicity*; Conditioning, Operant/drug effects; Conditioning, Operant/physiology; Disease Models, Animal; Dopamine Plasma Membrane Transport Proteins/genetics; Dopamine Plasma Membrane Transport Proteins/metabolism; Dopamine/metabolism*; Dose-Response Relationship, Drug; Gene Expression Regulation/drug effects; Gene Expression Regulation/genetics; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; Locomotion/drug effects; Locomotion/genetics; Manganese Compounds; Mutation/genetics*; Neurodegenerative Diseases/chemically induced*; Neurodegenerative Diseases/mortality; Survival Analysis; Telomerase/genetics*; Tyrosine 3-Monooxygenase/metabolism

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