There is a risk of exposure of aquatic organisms to silver nanoparticles (AgNPs) from discharges of municipal and industrial wastewater. In the present study, yellow perch (Perca flavescens) were exposed to environmentally relevant concentrations (1 mg/L and 100 mg/L) of AgNPs and silver ions (Ag ) in static-renewal experiments conducted over 96 h and 10 d. The greatest accumulation of total Ag occurred in the liver of P. flavescens, and there was >10-fold more accumulation in the treatments with Ag relative to the AgNP treatments. Residues of total Ag increased with concentration and duration of exposure in liver, gill, and muscle. Both exposures caused a 2-fold induction of gene expression for metallothionein (mt) in liver tissue after 96 h of exposure and reductions in levels of oxidized glutathione (GSSG) in liver after 10 d of exposure. Both AgNPs and Ag decreased the expression of heat-shock proteins (hsp70). Exposure to the high concentration of AgNPs for 10 d significantly increased lipid peroxidation in gill tissue, as indicated by the thiobarbituric acid reactive substances (TBARS) assay. There was a negative correlation between mean levels of GSSG and TBARS for both gill and liver tissue when data for all treatments were combined. It is significant that these biological responses were observed in P. flavescens exposed to AgNPs, even though accumulation of total Ag was at least 10-fold lower relative to the treatments with Ag . Environ Toxicol Chem 2017;36:1211-1220. © 2016 SETAC.

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Huntington’s disease (HD) is an inherited autosomal dominant neurodegenerative disorder that leads to progressive motor and cognitive impairment. There are currently no available disease modifying treatments for HD patients. We have previously shown that pharmacological blockade of metabotropic glutamate receptor 5 (mGluR5) signaling rescues motor deficits, improves cognitive impairments and mitigates HD neuropathology in male zQ175 HD mice. Mounting evidence indicates that sex may influence HD progression and we have recently reported a sex-specific pathological mGluR5 signaling in Alzheimer’s disease (AD) mice. Here, we compared the outcomes of treatment with the mGluR5 negative allosteric modulator CTEP (2-chloro-4-[2-[2,5-dimethyl-1-[4-(trifluoromethoxy)phenyl]imidazol-4-yl]ethynyl]pyridine) in both male and female symptomatic zQ175 mice. We found that female zQ175 mice required a longer treatment duration with CTEP than male mice to show improvement in their rotarod performance. Unlike males, chronic CTEP treatment did not improve the grip strength nor reverse the cognitive decline of female zQ175 mice. However, CTEP reduced the number of huntingtin aggregates, improved neuronal survival and decreased microglia activation in the striatum of both male and female zQ175 mice. Together, our results indicate that mGluR5 antagonism can reduce HD neuropathology in both male and female zQ175 HD mice, but sex has a clear impact on the efficacy of the treatment and must be taken into consideration for future HD drug development.