Nitrate and nitrite exposure leads to mild anxiogenic-like behavior and alters brain metabolomic profile in zebrafish.
Nitrate and nitrite exposure leads to mild anxiogenic-like behavior and alters brain metabolomic profile in zebrafish.
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DOI：
10.1371/journal.pone.0240070
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Hord NG
中科院分区：
文献类型：
--
作者：
García-Jaramillo M;Beaver LM;Truong L;Axton ER;Keller RM;Prater MC;Magnusson KR;Tanguay RL;Stevens JF;Hord NG
Dietary nitrate lowers blood pressure and improves athletic performance in humans, yet data supporting observations that it may increase cerebral blood flow and improve cognitive performance are mixed. We tested the hypothesis that nitrate and nitrite treatment would improve indicators of learning and cognitive performance in a zebrafish (Danio rerio) model. We utilized targeted and untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to examine the extent to which treatment resulted in changes in nitrate or nitrite concentrations in the brain and altered the brain metabolome. Fish were exposed to sodium nitrate (606.9 mg/L), sodium nitrite (19.5 mg/L), or control water for 2–4 weeks and free swim, startle response, and shuttle box assays were performed. Nitrate and nitrite treatment did not change fish weight, length, predator avoidance, or distance and velocity traveled in an unstressed environment. Nitrate- and nitrite-treated fish initially experienced more negative reinforcement and increased time to decision in the shuttle box assay, which is consistent with a decrease in associative learning or executive function however, over multiple trials, all treatment groups demonstrated behaviors associated with learning. Nitrate and nitrite treatment was associated with mild anxiogenic-like behavior but did not alter epinephrine, norepinephrine or dopamine levels. Targeted metabolomics analysis revealed no significant increase in brain nitrate or nitrite concentrations with treatment. Untargeted metabolomics analysis found 47 metabolites whose abundance was significantly altered in the brain with nitrate and nitrite treatment. Overall, the depletion in brain metabolites is plausibly associated with the regulation of neuronal activity including statistically significant reductions in the inhibitory neurotransmitter γ-aminobutyric acid (GABA; 18–19%), and its precursor, glutamine (17–22%). Nitrate treatment caused significant depletion in the brain concentration of fatty acids including linoleic acid (LA) by 50% and arachidonic acid (ARA) by 80%; nitrite treatment caused depletion of LA by ~90% and ARA by 60%, change which could alter the function of dopaminergic neurons and affect behavior. Nitrate and nitrite treatment did not adversely affect multiple parameters of zebrafish health. It is plausible that indirect NO-mediated mechanisms may be responsible for the nitrate and nitrite-mediated effects on the brain metabolome and behavior in zebrafish.
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影响因子：
5.2
作者：
Conley MN;Roberts C;Sharpton TJ;Iwaniec UT;Hord NG
通讯作者：
Hord NG
影响因子：
5
作者：
Croen, LA;Todoroff, K;Shaw, GM
通讯作者：
Shaw, GM
影响因子：
2.1
作者：
Dobashi, Shohei;Koyama, Katsuhiro;Horiuchi, Masahiro
通讯作者：
Horiuchi, Masahiro
DOI：
10.1080/00039896.1988.9935846
发表时间：
1988-03-01
期刊：
ARCHIVES OF ENVIRONMENTAL HEALTH
影响因子：
--
作者：
ARBUCKLE, TE;SHERMAN, GJ;LO, B
通讯作者：
LO, B
DOI：
10.1016/j.jchromb.2015.12.010
发表时间：
2016-04-15
影响因子：
3
作者：
Axton, Elizabeth R.;Hardardt, Elizabeth A.;Stevens, Jan F.
通讯作者：
Stevens, Jan F.