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研究生:程欣源
研究生(外文):Hsin-Yuan Cheng
論文名稱:懸浮微粒對中樞神經系統的毒性研究
論文名稱(外文):Central Nervous System Toxicity Induced by Particulate Matter
指導教授:鄭尊仁鄭尊仁引用關係
指導教授(外文):Tsun-Jen Cheng
口試委員:吳焜裕田履黛陳達夫
口試日期:2015-07-27
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2015
畢業學年度:103
語文別:英文
論文頁數:100
中文關鍵詞:柴油引擎微粒 (DEPs)氣管灌注 (I.T.)大氣細懸浮微粒 (PM2.5)呼吸暴露莫式水迷津空間學習與記憶
外文關鍵詞:Diesel exhaust particles (DEPs)Intratracheal instillation (I.T.)ambient fine particles (PM2.5)InhalationMorris water mazeSpatial learning and memory
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流行病學與毒理學研究皆有發現懸浮微粒不僅對心血管系統有影響,亦可能會對中樞神經系統產生負面的影響。多數的毒理學研究顯示其可能的機制為神經發炎反應進而造成行為改變。在本研究中,我們利用柴油引擎微粒 (DEPs) 探討急性暴露對中樞神經系統的毒性,也利用大氣細懸浮微粒 (PM2.5) 探討亞慢性暴露對中樞神經系統的影響。
本研究分為兩個部分,第一部分,C57BL/6 小鼠以氣管灌注的暴露方式暴露柴油引擎微粒,一周後進行莫式水迷津測試,再分別以學習期的逃脫時間、移動距離、累積相對距離和測試期的區域停留時間、區域經過次數、平均相對距離檢驗小鼠的空間學習與記憶能力。動物犧牲後以H&E染色進行腦組織病理檢驗。第二部分,C57BL/6 小鼠則以呼吸暴露的方式暴露大氣細懸浮微粒12周 (3個月),暴露完後一周進行莫式水迷津測試,同樣計算小鼠的空間學習與記憶能力。另外,小鼠藉由H&E染色進行腦組織病理檢驗。
第一部分研究結果顯示急性暴露於柴油引擎微粒會使小鼠於莫式水迷津學習期的表現較差,需要較長的逃脫時間與移動距離才能找到平台,累積相對距離也較長。腦組織病理檢驗未在暴露組與控制組間發現顯著差異且在正常範圍內。第二部分研究中,12周大氣細懸浮微粒暴露的平均質量濃度為11.9 μg/ m3。低濃度亞慢性呼吸暴露於大氣細懸浮微粒後,同樣在莫式水迷津學習期中發現其對小鼠的表現有所影響。小鼠的腦組織病理檢驗未在暴露組與控制組間發現顯著差異且在正常範圍內。
過去的研究發現懸浮微粒暴露後的行為變化可能與神經發炎有關,我們發現急性暴露於柴油引擎微粒或低濃度亞慢性呼吸暴露於細懸浮微粒都可以在莫式水迷津的學習期發現小鼠的表現有所變化,未來需要進一步的生化檢驗、腦部發炎細胞染色與組織病理檢驗去探討相關機制並驗證行為實驗的結果。


Epidemiological and toxicological studies have shown that particulate matter may not only have adverse effects in the cardiovascular system but also in the central nervous system (CNS). Most toxicological studies suggested that particulate matter may cause neuroinflammation and behavioral changes. Here, we used diesel exhaust particles (DEPs) to explore its acute CNS toxicity and also used ambient fine particles (PM2.5) to discuss sub-chronic exposure induced CNS toxicity.
There are two parts in this study. In the first part of study, C57BL/6 mice were given DEPs by intratracheal instillation. One week after exposure, Morris water maze was conducted. Escape latency, distanced moved and cumulative distance from the center of platform quadrant or platform in acquisition phase, percentage of time spent in target area, area crossing and average proximity from the center of platform quadrant or platform were calculated to examine spatial learning and memory. Histopathological examination was then conducted in the brain using H&E stain. In the second part of study, C57BL/6 mice were exposed to ambient PM2.5 by inhalation for 12 weeks (3 months). Morris water maze was then conducted one week after the end of exposure. Spatial learning and memory ability were tested. Histopathological examination was also conducted in the brain using H&E stain.
In the first part of study, results in Morris water maze test showed that acute exposure to DEPs may impair performance in acquisition phase. Mice required longer escape latency and distance moved to find the platform. Cumulative distance from the center of platform quadrant or platform was also longer. Mice histopathological examination found no significant difference between exposure and control group and was within normal limit. In the second part of study, the mean mass concentration for exposed ambient PM2.5 was 11.9 μg/ m3 during the exposure duration. Sub-chronic exposure to low concentration ambient PM2.5 may also impair performance in acquisition phase in Morris water maze test. Histopathological examination found no significant difference between exposure and control group and was within normal limit.
Previous studies found that behavioral changes after PM exposure may associated with neuroinflammation. We found that both acute exposure to DEPs and low concentration sub-chronic exposure to ambient PM2.5 may affect performance in acquisition phase in Morris water maze test in mice. Further biochemical examination, inflammatory cells staining in the brain and detailed histopathological were required to explore the mechanism and support current findings in behavioral changes.



中文摘要 i
Abstract ii
Contents iv
List of Tables vii
List of Figures viii

Chapter 1 Introduction 1
1.1 Background 1
1.2 Objectives 2

Chapter 2 Literature review 3
2.1 Particulate matter 3
2.2 Particulate matter induced cardiovascular effects and mechanism 4
2.3 Possible mechanism in particulate matter induced CNS effects 5
2.4 Morris water maze and related neuroanatomy 7
2.5 Epidemiological studies in particulate matter related CNS effects 8
2.6 Toxicological studies in particulate matter induced CNS effects 9
2.7 Susceptibility to particulate matter in CNS effects 12

Part 1. Study of central nervous toxicity induced by diesel exhaust particles (DEPs) 13

Chapter 3 Materials and Methods 14
3.1 Study protocol 14
3.2 Animals 16
3.3 Acute diesel exhaust particles (DEPs) exposure methods 16
3.4 DEPs exposure schedule 17
3.5 Morris water maze test 17
3.6 Histopathology 19
3.7 Statistics 19



Chapter 4 Results 20
4.1 Mice body weight 20
4.2 Acquisition phase of Morris water maze test 20
4.3 Probe test of Morris water maze test 22
4.4 Histopathology 23

Chapter 5 Discussion 24
5.1 DEPs dose and effects in neurofunctions 24
5.2 DEPs characterization and DEPs effects 25
5.3 CNS effects induced by DEPs 26
5.4 Mechanism involved in DEPs induced CNS effects 27
5.5 Spatial learning and memory 28
5.6 Limitations 29

Part 2. Study of central nervous toxicity induced by ambient fine particles (PM2.5) 30

Chapter 6 Materials and Methods 31
6.1 Study protocol 31
6.2 Animals 32
6.3 Ambient PM2.5 exposure 32
6.4 Ambient PM exposure monitoring and characterization 32
6.5 Ambient PM2.5 exposure schedule 34
6.6 Morris water maze test 34
6.7 Histopathology 35
6.8 Statistics 35

Chapter 7 Results 36
7.1 Mice body weight 36
7.2 PM2.5 and PM1 exposure monitoring and characterization 36
7.3 Acquisition phase of Morris water maze test 37
7.4 Probe test of Morris water maze test 37
7.5 Histopathology 38

Chapter 8 Discussion 39
8.1 Ambient PM exposure concentration and characterization 39
8.2 CNS effects induced by PM 40
8.3 Mechanism involved in PM induced CNS effects 42
8.4 Spatial learning and memory 43
8.5 Limitations 44

Chapter 9 Conclusions 45

References 46



1.Block, M.L. and L. Calderon-Garciduenas, Air pollution: mechanisms of neuroinflammation and CNS disease. Trends in Neurosciences, 2009. 32(9): p. 506-516.
2.Brook, R.D., et al., Air pollution and cardiovascular disease - A statement for healthcare professionals from the expert panel on population and prevention science of the American Heart Association. Circulation, 2004. 109(21): p. 2655-2671.
3.Kelly, F.J. and J.C. Fussell, Size, source and chemical composition as determinants of toxicity attributable to ambient particulate matter. Atmospheric Environment, 2012. 60: p. 504-526.
4.Pope, C.A., 3rd, et al., Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. Jama, 2002. 287(9): p. 1132-41.
5.Brook, R.D., et al., Particulate Matter Air Pollution and Cardiovascular Disease An Update to the Scientific Statement From the American Heart Association. Circulation, 2010. 121(21): p. 2331-2378.
6.Guerra, R., et al., Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum. Toxicology Letters, 2013. 222(2): p. 146-154.
7.Campbell, A., et al., Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain. Neurotoxicology, 2005. 26(1): p. 133-140.
8.Campbell, A., et al., Particulate Matter Induced Enhancement of Inflammatory Markers in the Brains of Apolipoprotein E Knockout Mice. Journal of Nanoscience and Nanotechnology, 2009. 9(8): p. 5099-5104.
9.Fonken, L.K., et al., Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology. Molecular Psychiatry, 2011. 16(10): p. 987-995.
10.EPA, U.S., Health Assessment Document for Diesel Engine Exhaust (Final 2002), O.o.R.a.D. U.S. Environmental Protection Agency, National Center for Environmental Assessment, Washington Office, Editor. 2002: Washington, DC, USA.
11.Ris, C., U.S. EPA health assessment for diesel engine exhaust: a review. Inhal Toxicol, 2007. 19 Suppl 1: p. 229-39.
12.Wichmann, H.E., Diesel exhaust particles. Inhal Toxicol, 2007. 19 Suppl 1: p. 241-4.
13.Ghio, A.J., C.B. Smith, and M.C. Madden, Diesel exhaust particles and airway inflammation. Curr Opin Pulm Med, 2012. 18(2): p. 144-50.
14.Win-Shwe, T.-T., et al., Novel object recognition ability in female mice following exposure to nanoparticle-rich diesel exhaust. Toxicology and Applied Pharmacology, 2012. 262(3): p. 355-362.
15.Win-Shwe, T.-T., et al., Spatial learning and memory function-related gene expression in the hippocampus of mouse exposed to nanoparticle-rich diesel exhaust. Neurotoxicology, 2008. 29(6): p. 940-947.
16.Win-Shwe, T.-T., et al., Nanoparticle-rich diesel exhaust affects hippocampal-dependent spatial learning and NMDA receptor subunit expression in female mice. Nanotoxicology, 2012. 6(5): p. 543-553.
17.Gerlofs-Nijland, M.E., et al., Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain. Particle and Fibre Toxicology, 2010. 7.
18.Levesque, S., et al., Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease. Journal of Neuroinflammation, 2011. 8.
19.Levesque, S., et al., Diesel Exhaust Activates and Primes Microglia: Air Pollution, Neuroinflammation, and Regulation of Dopaminergic Neurotoxicity. Environmental Health Perspectives, 2011. 119(8): p. 1149-1155.
20.Nemmar, A., et al., Diesel exhaust particles in lung acutely enhance experimental peripheral thrombosis. Circulation, 2003. 107(8): p. 1202-1208.
21.Robertson, S., et al., Diesel exhaust particulate induces pulmonary and systemic inflammation in rats without impairing endothelial function ex vivo or in vivo. Particle and Fibre Toxicology, 2012. 9.
22.Qin, L., et al., Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia, 2007. 55(5): p. 453-62.
23.Banks, W.A., Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des, 2005. 11(8): p. 973-84.
24.Banks, W.A., A.J. Kastin, and R.D. Broadwell, Passage of cytokines across the blood-brain barrier. Neuroimmunomodulation, 1995. 2(4): p. 241-8.
25.Hartz, A.M.S., et al., Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier. Faseb Journal, 2008. 22(8): p. 2723-2733.
26.Oppenheim, H.A., et al., Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice. Particle and Fibre Toxicology, 2013. 10.
27.Kao, Y.Y., et al., Demonstration of an olfactory bulb-brain translocation pathway for ZnO nanoparticles in rodent cells in vitro and in vivo. J Mol Neurosci, 2012. 48(2): p. 464-71.
28.Oberdorster, G., et al., Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicology, 2004. 16(6-7): p. 437-445.
29.Wang, B., et al., Transport of intranasally instilled fine Fe2O3 particles into the brain: micro-distribution, chemical states, and histopathological observation. Biol Trace Elem Res, 2007. 118(3): p. 233-43.
30.Elder, A., et al., Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environmental Health Perspectives, 2006. 114(8): p. 1172-1178.
31.Block, M.L. and J.S. Hong, Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism. Progress in Neurobiology, 2005. 76(2): p. 77-98.
32.Block, M.L., et al., Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase. Faseb Journal, 2004. 18(11): p. 1618-+.
33.Smith, J.A., et al., Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Research Bulletin, 2012. 87(1): p. 10-20.
34.O''Keefe, J. and J. Dostrovsky, The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res, 1971. 34(1): p. 171-5.
35.O''Keefe, J. and L. Nadel, The Hippocampus as a Cognitive Map. 1978.
36.Morris, R., DEVELOPMENTS OF A WATER-MAZE PROCEDURE FOR STUDYING SPATIAL-LEARNING IN THE RAT. Journal of Neuroscience Methods, 1984. 11(1): p. 47-60.
37.Florian, C. and P. Roullet, Hippocampal CA3-region is crucial for acquisition and memory consolidation in Morris water maze task in mice. Behavioural Brain Research, 2004. 154(2): p. 365-374.
38.Dash, P. and A. Moore, Neurochemistry and Molecular Neurobiology of Memory, in Handbook of Neurochemistry and Molecular Neurobiology. 2007, Springer. p. 709-738.
39.Moser, M.B., et al., Spatial learning with a minislab in the dorsal hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 1995. 92(21): p. 9697-9701.
40.de Bruin, J.P.C., et al., Place and Response Learning of Rats in a Morris Water Maze: Differential Effects of Fimbria Fornix and Medial Prefrontal Cortex Lesions. Neurobiology of Learning and Memory, 2001. 75(2): p. 164-178.
41.Fantie, B.D. and B. Kolb, AN EXAMINATION OF PREFRONTAL LESION SIZE AND THE EFFECTS OF CORTICAL GRAFTS ON PERFORMANCE OF THE MORRIS WATER TASK BY RATS. Psychobiology, 1990. 18(1): p. 74-80.
42.Frankland, P.W. and B. Bontempi, The organization of recent and remote memories. Nat Rev Neurosci, 2005. 6(2): p. 119-130.
43.Zhu, B., et al., Chronic lipopolysaccharide exposure induces cognitive dysfunction without affecting BDNF expression in the rat hippocampus. Exp Ther Med, 2014. 7(3): p. 750-754.
44.Wellenius, G.A., et al., Ambient Fine Particulate Matter Alters Cerebral Hemodynamics in the Elderly. Stroke, 2013. 44(6): p. 1533-+.
45.Kettunen, J., et al., Associations of fine and ultrafine particulate air pollution with stroke mortality in an area of low air pollution levels. Stroke, 2007. 38(3): p. 918-922.
46.Zeng, Y., et al., Associations of Environmental Factors With Elderly Health and Mortality in China. American Journal of Public Health, 2010. 100(2): p. 298-305.
47.Chen, J.-C. and J. Schwartz, Neurobehavioral effects of ambient air pollution on cognitive performance in US adults. Neurotoxicology, 2009. 30(2): p. 231-239.
48.Suglia, S.F., et al., Association of black carbon with cognition among children in a prospective birth cohort study. American Journal of Epidemiology, 2008. 167(3): p. 280-286.
49.Wang, S., et al., Association of Traffic-Related Air Pollution with Children''s Neurobehavioral Functions in Quanzhou, China. Environmental Health Perspectives, 2009. 117(10): p. 1612-1618.
50.Ranft, U., et al., Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly. Environmental Research, 2009. 109(8): p. 1004-1011.
51.Power, M.C., et al., Traffic-Related Air Pollution and Cognitive Function in a Cohort of Older Men. Environmental Health Perspectives, 2011. 119(5): p. 682-687.
52.Weuve, J., et al., Exposure to Particulate Air Pollution and Cognitive Decline in Older Women. Archives of Internal Medicine, 2012. 172(3): p. 219-227.
53.Jung, C.-R., Y.-T. Lin, and B.-F. Hwang, Ozone, Particulate Matter, and Newly Diagnosed Alzheimer''s Disease: A Population-Based Cohort Study in Taiwan. Journal of Alzheimers Disease, 2015. 44(2): p. 573-584.
54.Wu, Y.-C., et al., Association between air pollutants and dementia risk in the elderly. Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring, 2015. 1(2): p. 220-228.
55.Kilburn, K.H., Effects of diesel exhaust on neurobehavioral and pulmonary functions. Archives of Environmental Health, 2000. 55(1): p. 11-17.
56.Kleinman, M.T., et al., Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways. Toxicology Letters, 2008. 178(2): p. 127-130.
57.Veronesi, B., et al., Effects of subchronic exposure to concentrated ambient particles: VII. Degeneration of dopaminergic neurons in Apo E-/- mice. Inhalation Toxicology, 2005. 17(4-5): p. 235-241.
58.Guo, L., et al., Particulate matter (PM10) exposure induces endothelial dysfunction and inflammation in rat brain. Journal of Hazardous Materials, 2012. 213: p. 28-37.
59.Calderon-Garciduenas, L., et al., Brain inflammation and Alzheimer''s-like pathology in individuals exposed to severe air pollution. Toxicologic Pathology, 2004. 32(6): p. 650-658.
60.Calderon-Garciduenas, L., et al., Long-term Air Pollution Exposure Is Associated with Neuroinflammation, an Altered Innate Immune Response, Disruption of the Blood-Brain Barrier, Ultrafine Particulate Deposition, and Accumulation of Amyloid beta-42 and alpha-Synuclein in Children and Young Adults. Toxicologic Pathology, 2008. 36(2): p. 289-310.
61.Cruts, B., et al., Exposure to diesel exhaust induces changes in EEG in human volunteers. Particle and Fibre Toxicology, 2008. 5.
62.Hougaard, K.S., et al., Diesel Exhaust Particles: Effects on Neurofunction in Female Mice. Basic & Clinical Pharmacology & Toxicology, 2009. 105(2): p. 139-143.
63.Rodier, P.M., Vulnerable periods and processes during central nervous system development. Environmental Health Perspectives, 1994. 102: p. 121-124.
64.Block, M.L., et al., The outdoor air pollution and brain health workshop. Neurotoxicology, 2012. 33(5): p. 972-984.
65.Yokota, S., et al., Exposure to diesel exhaust during fetal period affects behavior and neurotransmitters in male offspring mice. Journal of Toxicological Sciences, 2013. 38(1): p. 13-23.
66.Yokota, S., et al., Effect of prenatal exposure to diesel exhaust on dopaminergic system in mice. Neuroscience Letters, 2009. 449(1): p. 38-41.
67.Suzuki, T., et al., In utero exposure to a low concentration of diesel exhaust affects spontaneous locomotor activity and monoaminergic system in male mice. Particle and Fibre Toxicology, 2010. 7.
68.Rajamani, K.T., et al., Prenatal and Early-Life Exposure to High-Level Diesel Exhaust Particles Leads to Increased Locomotor Activity and Repetitive Behaviors in Mice. Autism Research, 2013. 6(4): p. 248-257.
69.Allen, J.L., et al., Early Postnatal Exposure to Ultrafine Particulate Matter Air Pollution: Persistent Ventriculomegaly, Neurochemical Disruption, and Glial Activation Preferentially in Male Mice. Environ Health Perspect, 2014.
70.Allen, J.L., et al., Developmental Exposure to Concentrated Ambient Ultrafine Particulate Matter Air Pollution in Mice Results in Persistent and Sex-Dependent Behavioral Neurotoxicity and Glial Activation. Toxicol Sci, 2014.
71.Allen, J.L., et al., Developmental Exposure to Concentrated Ambient Particles and Preference for Immediate Reward in Mice. Environmental Health Perspectives, 2013. 121(1): p. 32-38.
72.Yokota, S., et al., Nasal instillation of nanoparticle-rich diesel exhaust particles slightly affects emotional behavior and learning capability in rats. Journal of Toxicological Sciences, 2011. 36(3): p. 267-276.
73.Sparkman, N.L. and R.W. Johnson, Neuroinflammation Associated with Aging Sensitizes the Brain to the Effects of Infection or Stress. Neuroimmunomodulation, 2008. 15(4-6): p. 323-330.
74.von Bernhardi, R., J.E. Tichauer, and J. Eugenin, Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders. Journal of Neurochemistry, 2010. 112(5): p. 1099-1114.
75.Scearce-Levie, K., Monitoring Spatial Learning and Memory in Alzheimer''s Disease Mouse Models Using the Morris Water Maze, in Alzheimer''s Disease and Frontotemporal Dementia: Methods and Protocols, E.D. Roberson, Editor. 2011. p. 191-205.
76.Jiang, J.K., G. Oberdorster, and P. Biswas, Characterization of size, surface charge, and agglomeration state of nanoparticle dispersions for toxicological studies. Journal of Nanoparticle Research, 2009. 11(1): p. 77-89.
77.Wahlsten, D., Chapter 3 - Tests of Mouse Behavior, in Mouse Behavioral Testing, D. Wahlsten, Editor. 2011, Academic Press: London. p. 39-51.
78.Alvin, V.T., Jr., Spatial Navigation (Water Maze) Tasks, in Methods of Behavior Analysis in Neuroscience, Second Edition. 2008, CRC Press. p. 267-280.
79.Gallagher, M., R. Burwell, and M. Burchinal, Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze. Behav Neurosci, 1993. 107(4): p. 618-26.
80.Seagrave, J., Mechanisms and implications of air pollution particle associations with chemokines. Toxicology and Applied Pharmacology, 2008. 232(3): p. 469-477.
81.Totlandsdal, A.I., et al., Differential effects of the particle core and organic extract of diesel exhaust particles. Toxicology Letters, 2012. 208(3): p. 262-268.
82.Singh, P., et al., Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice. Environmental Health Perspectives, 2004. 112(8): p. 820-825.
83.Technology, N.I.o.S., SRM 2975 - Diesel Particulate Matter, U.S.D. of and Commerce, Editors. Updated in 2013: Gaithersburg, MD, USA.
84.Allen, J.L., et al., Consequences of developmental exposure to concentrated ambient ultrafine particle air pollution combined with the adult paraquat and maneb model of the Parkinson''s disease phenotype in male mice. Neurotoxicology, 2014. 41: p. 80-88.
85.Sugamata, M., et al., Maternal diesel exhaust exposure damages newborn murine brains. Journal of Health Science, 2006. 52(1): p. 82-84.
86.Sugamata, M., et al., Maternal exposure to diesel exhaust leads to pathological similarity to autism in newborns. Journal of Health Science, 2006. 52(4): p. 486-488.
87.von Bohlen und Halbach, O., et al., Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice. Journal of Neuroscience Research, 2006. 83(4): p. 525-531.
88.von Bohlen und Halbach, O. and K. Unsicker, Morphological alterations in the amygdala and hippocampus of mice during ageing. European Journal of Neuroscience, 2002. 16(12): p. 2434-2440.
89.Bolding, K. and J.W. Rudy, Place learning in the Morris water task: Making the memory stick. Learning & Memory, 2006. 13(3): p. 278-286.
90.Paul, C.-M., G. Magda, and S. Abel, Spatial memory: Theoretical basis and comparative review on experimental methods in rodents. Behavioural Brain Research, 2009. 203(2): p. 151-164.
91.Yan, Y.H., et al., Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model. Toxicology and Applied Pharmacology, 2014. 281(2): p. 211-220.
92.Wu, C.-F., et al., Modeling horizontal and vertical variation in intraurban exposure to PM2.5 concentrations and compositions. Environmental Research, 2014. 133: p. 96-102.
93.Europe, W.H.O.R.O.f. and W.H. Organization, Air quality guidelines: global update 2005: particulate matter, ozone, nitrogen dioxide, and sulfur dioxide. 2006: World Health Organization.
94.Viana, M., et al., Source apportionment of particulate matter in Europe: A review of methods and results. Journal of Aerosol Science, 2008. 39(10): p. 827-849.
95.Watson, J.G., et al., Source apportionment: findings from the U.S. Supersites Program. J Air Waste Manag Assoc, 2008. 58(2): p. 265-88.
96.Harrison, R.M. and J.X. Yin, Particulate matter in the atmosphere: which particle properties are important for its effects on health? Science of the Total Environment, 2000. 249(1-3): p. 85-101.
97.Hueglin, C., et al., Chemical characterisation of PM2.5, PM10 and coarse particles at urban, near-city and rural sites in Switzerland. Atmospheric Environment, 2005. 39(4): p. 637-651.
98.Seagrave, J., et al., Lung toxicity of ambient particulate matter from southeastern U.S. sites with different contributing sources: relationships between composition and effects. Environ Health Perspect, 2006. 114(9): p. 1387-93.
99.Gutierrez-Castillo, M.E., et al., Effect of chemical composition on the induction of DNA damage by urban airborne particulate matter. Environ Mol Mutagen, 2006. 47(3): p. 199-211.
100.Sarkozi, L., et al., Subacute intratracheal exposure of rats to manganese nanoparticles: behavioral, electrophysiological, and general toxicological effects. Inhal Toxicol, 2009. 21 Suppl 1: p. 83-91.
101.Chen, W.-L., et al., Alterations in rat pulmonary phosphatidylcholines after chronic exposure to ambient fine particulate matter. Molecular BioSystems, 2014.
102.Harrison, F.E., A.H. Hosseini, and M.P. McDonald, Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks. Behavioural Brain Research, 2009. 198(1): p. 247-251.



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