Sex-Dependent Depression-Like Behavior Induced by Respiratory Administration of Aluminum Oxide Nanoparticles
Abstract
:1. Introduction
2. Methods
2.1. Nanomaterial and Animals
2.2. Animal Treatment
2.3. Open-Field Tests
2.4. Forced Swimming Test
2.5. RNA Isolation and Quantitative Real-Time PCR Assay
2.6. Pathological Analysis
2.7. Aluminum Burden
2.8. Metabolomics Analysis
2.9. Data Analysis
3. Results
3.1. Female Mice Demonstrated Depressive-Like Behavior Following Al2O3 NP Exposure.
3.2. Aluminum Burden Varied in Brain and Lung Tissues of Mice
3.3. Pathological Alterations of Lung but not Brain Tissues of Mice Were Observed
Group | Lesion Severity Grade | Average Severity Grade | |||
---|---|---|---|---|---|
1 | 2 | 3 | 4 | ||
male control | 4 | 1 | |||
female control | 4 | 1 | |||
male nano-Al2O3 | 3 | 1 | 2.25 ± 0.50 * | ||
female nano-Al2O3 | 2 | 2 | 2.5 ± 0.58 * |
3.4. Expressions of Mental Disorder Involved Genes Were Modulated in a Sex-Dependent Manner
3.5. Metabolomics Analysis Explored the Potential Role of Glutamate
Control | Treatment | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Male | Female | Male | Female | F Value | p Value | |||||
Fold Change | Fold Change | Fold Change | Fold Change | Treatment | Sex | Interaction | Treatment | Sex | Interaction | |
SNAP29 | 1.03 ± 0.10 | 1.02 ± 0.12 | 0.95 ± 0.11 | 0.62±0.14 *,# | 24.64 | 12.36 | 10.95 & | <0.0001 | 0.0022 | 0.0035 |
UFD1L | 1.01 ± 0.07 | 1.02 ± 0.06 | 0.61 ± 0.08 * | 0.65±0.08 * | 167.00 | 0.7042 | 0.2535 | <0.0001 | 0.4113 | 0.6201 |
ZDHHC8 | 1.04 ± 0.05 | 1.05 ± 0.07 | 0.95 ± 0.07 * | 0.58±0.06 *,# | 131.40 | 41.09 | 46.23 & | <0.0001 | <0.0001 | <0.0001 |
PDLIM5 | 1.01 ± 0.08 | 1.05 ± 0.10 | 0.71 ± 0.10 * | 0.82±0.14 * | 36.64 | 2.935 | 0.639 | <0.0001 | 0.1022 | 0.4334 |
HSPA1A | 1.06 ± 0.10 | 0.99 ± 0.07 | 0.54 ± 0.11 * | 0.56±0.09 * | 154.30 | 0.4273 | 1.385 | <0.0001 | 0.5207 | 0.2531 |
PTEN | 0.99 ± 0.08 | 1.03 ± 0.09 | 0.63 ± 0.11 * | 0.67±0.12 * | 75.86 | 0.94 | 0.00 | <0.0001 | 0.3447 | 1.0000 |
GDNF | 1.01 ± 0.07 | 0.98 ± 0.05 | 0.65 ± 0.06 * | 0.32±0.14 *,# | 204.00 | 25.41 | 17.65 & | <0.0001 | <0.0001 | 0.0004 |
SOD2 | 0.97 ± 0.06 | 0.99 ± 0.08 | 0.67 ± 0.12 * | 0.56±0.07 * | 109.10 | 1.66 | 3.46 | <0.0001 | 0.2125 | 0.0776 |
GNAS | 1.01 ± 0.09 | 1.06 ± 0.12 | 0.88 ± 0.15 | 0.70±0.14 *,# | 22.30 | 1.57 | 4.91 & | 0.0001 | 0.2247 | 0.0384 |
NOS3 | 0.96 ± 0.11 | 1.00 ± 0.04 | 0.71 ± 0.08 * | 0.93±0.15 # | 14.42 | 9.52 | 4.56 & | 0.0011 | 0.0058 | 0.0452 |
DLST | 1.01 ± 0.04 | 0.97 ± 0.06 | 0.91 ± 0.12 | 0.87±0.06 | 10.34 | 1.66 | 0.00 | 0.0043 | 0.2130 | 1.0000 |
GRIN2A | 0.97 ± 0.08 | 1.01 ± 0.06 | 1.10 ± 0.18 | 2.78±0.17 *,# | 423.70 | 317.70 | 288.20 & | <0.0001 | <0.0001 | <0.0001 |
DGKH | 1.01 ± 0.04 | 1.06 ± 0.09 | 2.14 ± 0.09 * | 0.72±0.06 *,# | 175.00 | 526.21 | 605.94 & | <0.0001 | <0.0001 | <0.0001 |
MT2A | 1.01 ± 0.07 | 1.02 ± 0.15 | 1.98 ± 0.07 * | 2.34±0.13 *,# | 639.50 | 16.70 | 14.94 & | 0.0010 | 0.0006 | <0.0001 |
CACNA1G | 1.04 ± 0.07 | 1.03 ± 0.06 | 2.77 ± 0.13 * | 0.75±0.12 *,# | 516.75 | 938.68 | 887.50 & | <0.0001 | <0.0001 | <0.0001 |
KCNQ | 1.00 ± 0.04 | 0.97 ± 0.08 | 2.86 ± 0.10 * | 0.72±0.11 *,# | 317.03 | 621.19 | 609.14 & | <0.0001 | <0.0001 | <0.0001 |
Metabolite | HMDB ID | Fold Change | Male Al2O3 NPs vs. Male Control | Female Al2O3 NPs vs. Male Control | |||||
---|---|---|---|---|---|---|---|---|---|
Male Al2O3 NPs | Female Control | Female Al2O3 NPs | F Value | p Value | F Value | p Value | |||
L-Serine | HMDB00187 | 1.98 | 1.03 | 4.26 # | 13.63 | 0.002 | 53.54 | <0.0001 | |
Dihydroxy acetone Phosphate | HMDB01473 | - | 0.83 | 2.97 # | 0.43 | 0.5261 | 14.9 | 0.0017 | |
Inosine | HMDB00195 | 2.05 | 1.14 | 2.61 | 12.68 | 0.0022 | 13.01 | 0.0019 | |
Prostaglandin E2 | HMDB01220 | 2.43 | 1.27 | 4.02 | 22.31 | 0.0001 | 49.69 | <0.0001 | |
Acetyl-L-Carnitine | HMDB00201 | 2.37 | 0.96 | 3.86 | 28.74 | <0.0001 | 37.21 | <0.0001 | |
Pyroglutamic Acid | HMDB00267 | 2.53 | 0.89 | 0.52 # | 32.57 | <0.0001 | 24.52 | <0.0001 | |
Riboflavin | HMDB00244 | 3.83 | 1.07 | 2.18 | 36.53 | <0.0001 | 27.73 | <0.0001 | |
Inosine 5-Monophosphate | HMDB00175 | 1.89 | 0.93 | 1.68 | 11.42 | 0.0026 | 9.52 | 0.0058 | |
l-Glutamic Acid | HMDB00148 | - | 1.08 | 0.17 # | 1.69 | 0.2125 | 103.89 | <0.0001 | |
7b-Hydroxycholesterol | HMDB06119 | 0.48 | 0.77 | - | 28.49 | <0.0001 | 0.89 | 0.4213 | |
2-Hydroxyestrone | HMDB00343 | - | 0.98 | 0.48 | 0.25 | 0.6178 | 41.25 | <0.0001 | |
Dl-Glyceraldehyde | HMDB01051 | 0.3 | 1.06 | 0.46 | 59.77 | <0.0001 | 38.56 | <0.0001 | |
Petroselinic Acid | HMDB02080 | 0.21 | 1.18 | 0.48 | 75.86 | <0.0001 | 42.59 | <0.0001 |
4. Discussion
5. Conclusions
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interest
References
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Zhang, X.; Xu, Y.; Zhou, L.; Zhang, C.; Meng, Q.; Wu, S.; Wang, S.; Ding, Z.; Chen, X.; Li, X.; et al. Sex-Dependent Depression-Like Behavior Induced by Respiratory Administration of Aluminum Oxide Nanoparticles. Int. J. Environ. Res. Public Health 2015, 12, 15692-15705. https://doi.org/10.3390/ijerph121215011
Zhang X, Xu Y, Zhou L, Zhang C, Meng Q, Wu S, Wang S, Ding Z, Chen X, Li X, et al. Sex-Dependent Depression-Like Behavior Induced by Respiratory Administration of Aluminum Oxide Nanoparticles. International Journal of Environmental Research and Public Health. 2015; 12(12):15692-15705. https://doi.org/10.3390/ijerph121215011
Chicago/Turabian StyleZhang, Xin, Yan Xu, Lian Zhou, Chengcheng Zhang, Qingtao Meng, Shenshen Wu, Shizhi Wang, Zhen Ding, Xiaodong Chen, Xiaobo Li, and et al. 2015. "Sex-Dependent Depression-Like Behavior Induced by Respiratory Administration of Aluminum Oxide Nanoparticles" International Journal of Environmental Research and Public Health 12, no. 12: 15692-15705. https://doi.org/10.3390/ijerph121215011