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研究生:柴培睿
研究生(外文):Pei-Jui chai
論文名稱:以自發性高血壓大鼠亞慢性暴露大氣微粒對神經毒性的影響
論文名稱(外文):Neurotoxicity induced by subchronic inhalation exposure to ambient particulate matter in Spontaneously Hypertensive Rats
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:陳鑫昌莊校奇
口試委員(外文):Hsin-Chang ChenHsiao-Chi Chuang
口試日期:2018-07-23
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:2018
畢業學年度:106
語文別:中文
論文頁數:105
中文關鍵詞:大氣細懸浮微粒神經毒性氧化壓力Tau蛋白莫氏水迷津
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許多流行病學與毒理學研究皆證實暴露於大氣懸浮微粒(Particulate matter, PM)會增加中樞神經的氧化壓力,進而引起神經退行性疾病,包括阿茲海默症(Alzheimer’s disease, AD),阿茲海默症在腦中的主要病理特徵,是由乙型類澱粉蛋白(Amyloid-beta, Aβ)沈積所形成老年斑塊(Senile plaques),以及由過度磷酸化Tau蛋白(Hyperphosphorylated Tau protein)聚集所組成神經纖維纏結(Neurofibrillary tangles, NFTs),另外有研究也指出氧化壓力會誘導Tau蛋白過度磷酸化以及NFTs形成,進而引起阿茲海默症,此外,高血壓被認為是阿茲海默症的危險因子之一,因此本研究使用自發性高血壓動物模式,並假設暴露於懸浮微粒會加速自發性高血壓大鼠(Spontaneously hypertensive rats, SHR)在腦中形成阿茲海默症病徵,因此本研究欲探討亞慢性暴露大氣懸浮微粒後,氧化壓力指標和阿茲海默症病徵在腦中的變化。
本研究以8周大的SHR使用台北空氣污染暴露系統(Taipei Air Pollution Exposure System, TAPES)進行三個月與六個月的全身性呼吸暴露,此系統可提供動物全身暴露於連續、非濃縮的真實大氣懸浮微粒,暴露三個月後進行莫氏水迷津(Morris water maze, MWM),MWM完成後,再進行暴露,待總暴露時間到達六個月,暴露結束後大鼠進行犧牲,取出腦組織,細分為嗅球(Olfactory bulb)、小腦(Cerebellum)、海馬迴(Hippocampus)以及皮質(Cerebral cortex)四個腦區,針對四個不同腦區測定氧化壓力指標丙二醛(Malondialdehyde, MDA)以及阿茲海默症病徵指標總Tau蛋白(Total Tau protein, t-Tau)和磷酸化Tau蛋白(Phosphorylated Tau protein, P-tau)。
本研究大鼠暴露前三個月PM2.5之平均質量濃度為8.6 μg/m3,暴露後三個月PM2.5之平均質量濃度為10.8 μg/m3,行為實驗結果顯示知識採集階段和空間探索實驗在控制組和暴露組之間皆無顯著差異,而控制組以及暴露組有著一條合理的學習曲線;在氧化壓力指標MDA的部分,暴露三個月在四個腦區皆無顯著差異,暴露六個月在嗅球、海馬迴及皮質則顯著上升;在阿茲海默症指標Tau蛋白的部分,暴露三個月t-Tau和p-Tau蛋白表現量在嗅球有顯著上升,而暴露六個月在四個腦區皆無顯著差異;在組織病理切片的部分,肺部在暴露三和六個月的控制組與暴露組皆無明顯的病理變化,而腦部暴露六個月的控制組與暴露組也無明顯的病理變化。
研究結果顯示亞慢性呼吸暴露大氣懸浮微粒會誘導腦中的氧化壓力上升與Tau蛋白增加,然而三個月大氣懸浮微粒暴露並未對SHR的空間學習及記憶功能造成影響,本研究說明呼吸暴露大氣懸浮微粒造成中樞神經產生毒性的可能機制,但本實驗所探討與中樞神經毒性相關的指標仍不足,因此未來的研究需要更進一步來釐清大氣懸浮微粒對中樞神經的影響。
Recently, many studies have shown that exposure to particulate matter (PM) may induce oxidative stress in the central nervous system (CNS) and contribute to neurodegenerative diseases, such as Alzheimer’s disease (AD). The major pathological characteristics of AD brain are senile plaque of amyloid-beta (Aβ) and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein. Some findings have also indicated the oxidative stress would induce Tau protein hyperphosphorylation and NFTs formation and contribute to AD. Moreover, hypertension is a well-known risk factor for Alzheimer’s disease. Thus, we hypothesized that ambient particulate matter could accelerate Alzheimer’s disease-like effects in spontaneously hypertensive rats (SHR). In the experiment, we use SHR to explore the relationship between PM exposure and markers of oxidative stress and markers of AD through subchronic inhalation.
8-week-old male SHR were exposed to continuous, non-concentrated, real world PM2.5 using Taipei Air Pollution Exposure System (TAPES) for 3 and 6 months. After 3 months exposure, Morris Water Maze (MWM) was conducted. Afterwards, the rats were proceeded an another 3 months exposure of PM2.5 for a total of 6 months. After the exposure, the brain tissue, including olfactory bulb, cerebellum, hippocampus and cerebral cortex, were collected. The level of malondialdehyde (MDA), maker of oxidative stress, was determined by LC-MS/MS. Total Tau protein (t-Tau) and phosphorylated Tau protein (p-Tau), markers of AD, were assessed by Western blot.
The mean mass concentration of PM2.5 was 8.6 μg/m3 from the first 3 months exposure and 10.8 μg/m3 from the second 3 months exposure. Our results showed that MWM didn’t have any differences compared to control groups after exposure for 3 months. Both control and exposure groups showed a reasonable learning curve of escape latency in acquisition phase. In MDA, the level of MDA significantly increased in olfactory bulb, hippocampus and cerebral cortex after 6 months exposure. In 3 months exposure, the MDA level in four brain regions didn’t find any significant differences between control and exposure group. The result of Tau protein expression showed that the level of t-Tau protein expression, as well as p-Tau protein expression, significantly increased in olfactory bulb in 3 months exposure. However, in 6 months exposure, the level of t-Tau and p-Tau protein expression didn’t find any significant differences between control and exposure group in four brain regions. We found no significant differences between the control and the exposure group in histopathology of lung from 3 and 6 months exposure and brain from 6 months exposure.
In conclusion, our study indicated the subchronic exposure to ambient particles would induce oxidative stress and Tau protein in brain. However, exposure to ambient particles for 3 months may not impair spatial learning and memory in SHR. Our study revealed the possible mechanism of PM exposure by inhalation and neurotoxicity in CNS. Nevertheless, our study didn’t investigate many neurotoxicity-related markers in CNS. Further study should be conducted to explore the more markers related to neurotoxicity in CNS and clarify the relationship between PM and neurotoxicity in CNS.
中文摘要 I
Abstract III
第一章 前言與研究目的 1
1.1 前言 1
1.2 研究目的 2
第二章 文獻回顧 3
2.1 微粒暴露對健康的影響 3
2.2 微粒暴露與中樞神經毒性 5
2.3 微粒與神經退化性疾病 7
2.4 微粒暴露與氧化壓力 10
2.5 自發性高血壓大鼠 12
第三章 材料與方法 15
3.1 實驗動物 15
3.2 實驗流程與架構 15
3.3 大氣懸浮微粒暴露 17
3.3.1 台北空氣污染暴露系統 17
3.3.2 大氣微粒監測 17
3.3.3 成分分析 18
3.4 莫氏水迷津 19
3.5 MDA分析 21
3.5.1 MDA萃取 21
3.5.2 標準溶液之配製 21
3.5.3 基質效應 21
3.5.4 LC-MS/MS 分析方法 22
3.6 Total Tau蛋白與phosphorylated Tau蛋白表現量分析 24
3.6.1 蛋白質萃取 24
3.6.2 蛋白質定量 24
3.6.3 西方點墨法分析與流程 25
3.6.4 半定量分析 26
3.7 組織病理 27
3.8 統計方法 27
第四章 結果 28
4.1 實驗動物體重 28
4.2 微粒濃度與元素組成 28
4.2.1 暴露期間微粒濃度 28
4.2.2 暴露期間微粒之元素組成 28
4.3 莫氏水迷津 29
4.4 腦部MDA 30
4.4.1 基質效應之評估 30
4.4.2 各腦區之MDA濃度 30
4.5 腦部Tau蛋白表現 31
4.5.1 各腦區t-Tau蛋白表現量 31
4.5.2 各腦區p-Tau蛋白表現量 31
4.5.3 各腦區p-Tau蛋白與t-Tau蛋白表現量比值 31
4.6 組織病理切片 32
第五章 討論 33
5.1 全身性呼吸暴露 34
5.2 PM2.5濃度及特性 35
5.3 微粒對空間學習及記憶能力之影響 36
5.4 微粒對MDA之影響 37
5.5 微粒對Tau蛋白之影響 39
5.6 組織病理切片 42
5.7 研究限制 43
第六章 結論 44
第七章 參考資料 45
Ajmani, G.S., Suh, H.H., Pinto, J.M., 2016. Effects of Ambient Air Pollution Exposure on Olfaction: A Review. Environmental health perspectives 124, 1683-1693.
Alonso Adel, C., Mederlyova, A., Novak, M., Grundke-Iqbal, I., Iqbal, K., 2004. Promotion of hyperphosphorylation by frontotemporal dementia tau mutations. The Journal of biological chemistry 279, 34873-34881.
Andreadis, A., Brown, W.M., Kosik, K.S., 1992. Structure and novel exons of the human tau gene. Biochemistry 31, 10626-10633.
Anoopkumar-Dukie, S., Walker, R.B., Daya, S., 2001. A sensitive and reliable method for the detection of lipid peroxidation in biological tissues. The Journal of pharmacy and pharmacology 53, 263-266.
Attems, J., Walker, L., Jellinger, K.A., 2014. Olfactory bulb involvement in neurodegenerative diseases. Acta neuropathologica 127, 459-475.
Aungudornpukdee, P., Vichit-Vadakan, N., Taneepanichskul, S., 2010. Factors related to short-term memory dysfunction in children residing near a Petrochemical Industrial Estate. Journal of the Medical Association of Thailand = Chotmaihet thangphaet 93, 285-292.
Bhatt, D.P., Puig, K.L., Gorr, M.W., Wold, L.E., Combs, C.K., 2015. A pilot study to assess effects of long-term inhalation of airborne particulate matter on early Alzheimer-like changes in the mouse brain. PloS one 10, e0127102.
Biernat, J., Mandelkow, E.M., 1999. The development of cell processes induced by tau protein requires phosphorylation of serine 262 and 356 in the repeat domain and is inhibited by phosphorylation in the proline-rich domains. Molecular biology of the cell 10, 727-740.
Blennow, K., Hampel, H., 2003. CSF markers for incipient Alzheimer''s disease. The Lancet Neurology 2, 605-613.
Block, M.L., Calderon-Garciduenas, L., 2009. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends in neurosciences 32, 506-516.
Bos, I., De Boever, P., Emmerechts, J., Buekers, J., Vanoirbeek, J., Meeusen, R., Van Poppel, M., Nemery, B., Nawrot, T., Panis, L.I., 2012. Changed gene expression in brains of mice exposed to traffic in a highway tunnel. Inhalation toxicology 24, 676-686.
Brook, R.D., Franklin, B., Cascio, W., Hong, Y., Howard, G., Lipsett, M., Luepker, R., Mittleman, M., Samet, J., Smith, S.C., Jr., Tager, I., 2004. 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 109, 2655-2671.
Buee-Scherrer, V., Condamines, O., Mourton-Gilles, C., Jakes, R., Goedert, M., Pau, B., Delacourte, A., 1996. AD2, a phosphorylation-dependent monoclonal antibody directed against tau proteins found in Alzheimer''s disease. Brain research Molecular brain research 39, 79-88.
Calderon-Garciduenas, L., Azzarelli, B., Acuna, H., Garcia, R., Gambling, T.M., Osnaya, N., Monroy, S., MR, D.E.L.T., Carson, J.L., Villarreal-Calderon, A., Rewcastle, B., 2002. Air pollution and brain damage. Toxicologic pathology 30, 373-389.
Calderon-Garciduenas, L., Engle, R., Mora-Tiscareno, A., Styner, M., Gomez-Garza, G., Zhu, H., Jewells, V., Torres-Jardon, R., Romero, L., Monroy-Acosta, M.E., Bryant, C., Gonzalez-Gonzalez, L.O., Medina-Cortina, H., D''Angiulli, A., 2011. Exposure to severe urban air pollution influences cognitive outcomes, brain volume and systemic inflammation in clinically healthy children. Brain and cognition 77, 345-355.
Calderon-Garciduenas, L., Kavanaugh, M., Block, M., D''Angiulli, A., Delgado-Chavez, R., Torres-Jardon, R., Gonzalez-Maciel, A., Reynoso-Robles, R., Osnaya, N., Villarreal-Calderon, R., Guo, R., Hua, Z., Zhu, H., Perry, G., Diaz, P., 2012. Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults. Journal of Alzheimer''s disease : JAD 28, 93-107.
Calderon-Garciduenas, L., Maronpot, R.R., Torres-Jardon, R., Henriquez-Roldan, C., Schoonhoven, R., Acuna-Ayala, H., Villarreal-Calderon, A., Nakamura, J., Fernando, R., Reed, W., Azzarelli, B., Swenberg, J.A., 2003. DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration. Toxicologic pathology 31, 524-538.
Calderon-Garciduenas, L., Mora-Tiscareno, A., Ontiveros, E., Gomez-Garza, G., Barragan-Mejia, G., Broadway, J., Chapman, S., Valencia-Salazar, G., Jewells, V., Maronpot, R.R., Henriquez-Roldan, C., Perez-Guille, B., Torres-Jardon, R., Herrit, L., Brooks, D., Osnaya-Brizuela, N., Monroy, M.E., Gonzalez-Maciel, A., Reynoso-Robles, R., Villarreal-Calderon, R., Solt, A.C., Engle, R.W., 2008a. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain and cognition 68, 117-127.
Calderon-Garciduenas, L., Reed, W., Maronpot, R.R., Henriquez-Roldan, C., Delgado-Chavez, R., Calderon-Garciduenas, A., Dragustinovis, I., Franco-Lira, M., Aragon-Flores, M., Solt, A.C., Altenburg, M., Torres-Jardon, R., Swenberg, J.A., 2004. Brain inflammation and Alzheimer''s-like pathology in individuals exposed to severe air pollution. Toxicologic pathology 32, 650-658.
Calderon-Garciduenas, L., Solt, A.C., Henriquez-Roldan, C., Torres-Jardon, R., Nuse, B., Herritt, L., Villarreal-Calderon, R., Osnaya, N., Stone, I., Garcia, R., Brooks, D.M., Gonzalez-Maciel, A., Reynoso-Robles, R., Delgado-Chavez, R., Reed, W., 2008b. 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 36, 289-310.
Campbell, A., Oldham, M., Becaria, A., Bondy, S.C., Meacher, D., Sioutas, C., Misra, C., Mendez, L.B., Kleinman, M., 2005. Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain. Neurotoxicology 26, 133-140.
Ceconi, C., Cargnoni, A., Pasini, E., Condorelli, E., Curello, S., Ferrari, R., 1991. Evaluation of phospholipid peroxidation as malondialdehyde during myocardial ischemia and reperfusion injury. The American journal of physiology 260, H1057-1061.
Chen, L., Lee, H.M., Greeley, G.H., Jr., Englander, E.W., 2007. Accumulation of oxidatively generated DNA damage in the brain: a mechanism of neurotoxicity. Free radical biology & medicine 42, 385-393.
Cho, J.H., Johnson, G.V., 2004. Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3beta (GSK3beta) plays a critical role in regulating tau''s ability to bind and stabilize microtubules. Journal of neurochemistry 88, 349-358.
Chuang, C., 2017. Ambient particles exposure and progress of Alzheimer''s disease in 3xTg-AD mice: a pilot study.
Cleveland, D.W., Hwo, S.Y., Kirschner, M.W., 1977. Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly. Journal of molecular biology 116, 227-247.
Cole, T.B., Coburn, J., Dao, K., Roque, P., Chang, Y.C., Kalia, V., Guilarte, T.R., Dziedzic, J., Costa, L.G., 2016. Sex and genetic differences in the effects of acute diesel exhaust exposure on inflammation and oxidative stress in mouse brain. Toxicology 374, 1-9.
Cordis, G.A., Das, D.K., Riedel, W., 1998. High-performance liquid chromatographic peak identification of 2,4-dinitrophenylhydrazine derivatives of lipid peroxidation aldehydes by photodiode array detection. Journal of chromatography A 798, 117-123.
Costa, L.G., Cole, T.B., Coburn, J., Chang, Y.C., Dao, K., Roque, P., 2014. Neurotoxicants are in the air: convergence of human, animal, and in vitro studies on the effects of air pollution on the brain. BioMed research international 2014, 736385.
Costa, L.G., Cole, T.B., Coburn, J., Chang, Y.C., Dao, K., Roque, P.J., 2017. Neurotoxicity of traffic-related air pollution. Neurotoxicology 59, 133-139.
Duron, E., Hanon, O., 2008. Hypertension, cognitive decline and dementia. Archives of cardiovascular diseases 101, 181-189.
Ebneth, A., Godemann, R., Stamer, K., Illenberger, S., Trinczek, B., Mandelkow, E., 1998. Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer''s disease. The Journal of cell biology 143, 777-794.
Elder, A., Gelein, R., Silva, V., Feikert, T., Opanashuk, L., Carter, J., Potter, R., Maynard, A., Ito, Y., Finkelstein, J., Oberdorster, G., 2006. Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environmental health perspectives 114, 1172-1178.
Evans, D.B., Rank, K.B., Bhattacharya, K., Thomsen, D.R., Gurney, M.E., Sharma, S.K., 2000. Tau phosphorylation at serine 396 and serine 404 by human recombinant tau protein kinase II inhibits tau''s ability to promote microtubule assembly. The Journal of biological chemistry 275, 24977-24983.
Fagundes, L.S., Fleck Ada, S., Zanchi, A.C., Saldiva, P.H., Rhoden, C.R., 2015. Direct contact with particulate matter increases oxidative stress in different brain structures. Inhalation toxicology 27, 462-467.
Fath, T., Eidenmuller, J., Brandt, R., 2002. Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzheimer''s disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 22, 9733-9741.
Fonken, L.K., Xu, X., Weil, Z.M., Chen, G., Sun, Q., Rajagopalan, S., Nelson, R.J., 2011. Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology. Molecular psychiatry 16, 987-995, 973.
Forstl, H., Kurz, A., 1999. Clinical features of Alzheimer''s disease. European archives of psychiatry and clinical neuroscience 249, 288-290.
Gao, C., Holscher, C., Liu, Y., Li, L., 2011. GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease. Reviews in the neurosciences 23, 1-11.
Genc, S., Zadeoglulari, Z., Fuss, S.H., Genc, K., 2012. The adverse effects of air pollution on the nervous system. Journal of toxicology 2012, 782462.
Gerlofs-Nijland, M.E., Boere, A.J., Leseman, D.L., Dormans, J.A., Sandstrom, T., Salonen, R.O., van Bree, L., Cassee, F.R., 2005. Effects of particulate matter on the pulmonary and vascular system: time course in spontaneously hypertensive rats. Particle and fibre toxicology 2, 2.
Gerlofs-Nijland, M.E., van Berlo, D., Cassee, F.R., Schins, R.P., Wang, K., Campbell, A., 2010. Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain. Particle and fibre toxicology 7, 12.
Goedert, M., Spillantini, M.G., 2006. A century of Alzheimer''s disease. Science (New York, NY) 314, 777-781.
Gong, C., Iqbal, K., 2008. Hyperphosphorylation of Microtubule-Associated Protein Tau: A Promising Therapeutic Target for Alzheimer Disease. Current medicinal chemistry 15, 2321-2328.
Grotto, D., Maria, L.S., Valentini, J., Paniz, C., Schmitt, G., Garcia, S.C., Pomblum, V.J., Rocha, J.B.T., Farina, M., 2009. Importance of the lipid peroxidation biomarkers and methodological aspects FOR malondialdehyde quantification. Química Nova 32, 169-174.
Grunblatt, E., Bartl, J., Iuhos, D.I., Knezovic, A., Trkulja, V., Riederer, P., Walitza, S., Salkovic-Petrisic, M., 2015. Characterization of cognitive deficits in spontaneously hypertensive rats, accompanied by brain insulin receptor dysfunction. Journal of molecular psychiatry 3, 6.
Guerra, R., Vera-Aguilar, E., Uribe-Ramirez, M., Gookin, G., Camacho, J., Osornio-Vargas, A., Mugica-Alvarez, V., Angulo-Olais, R., Campbell, A., Froines, J., Kleinman, T., De Vizcaya-Ruiz, A., 2013. Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum. Toxicology letters 222, 146-154.
Guo, L., Zhu, N., Guo, Z., Li, G.K., Chen, C., Sang, N., Yao, Q.C., 2012. Particulate matter (PM10) exposure induces endothelial dysfunction and inflammation in rat brain. Journal of hazardous materials 213-214, 28-37.
Hallback, M., Weiss, L., 1977. Mechanisms of spontaneous hypertension in rats. The Medical clinics of North America 61, 593-609.
Hamano, T., Gendron, T.F., Causevic, E., Yen, S.H., Lin, W.L., Isidoro, C., Deture, M., Ko, L.W., 2008. Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild-type tau expression. The European journal of neuroscience 27, 1119-1130.
Hampel, H., Blennow, K., Shaw, L.M., Hoessler, Y.C., Zetterberg, H., Trojanowski, J.Q., 2010. Total and Phosphorylated Tau Protein as Biological Markers of Alzheimer''s Disease. Experimental gerontology 45, 30.
Hanes, J., Zilka, N., Bartkova, M., Caletkova, M., Dobrota, D., Novak, M., 2009. Rat tau proteome consists of six tau isoforms: implication for animal models of human tauopathies. Journal of neurochemistry 108, 1167-1176.
Hanger, D.P., Anderton, B.H., Noble, W., 2009. Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends in molecular medicine 15, 112-119.
Hernandez, F., Lucas, J.J., Avila, J., 2013. GSK3 and tau: two convergence points in Alzheimer''s disease. Journal of Alzheimer''s disease : JAD 33 Suppl 1, S141-144.
Ho, Y.S., Yang, X., Yeung, S.C., Chiu, K., Lau, C.F., Tsang, A.W., Mak, J.C., Chang, R.C., 2012. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats. PloS one 7, e36752.
Hu, W., Wu, F., Zhang, Y., Gong, C.X., Iqbal, K., Liu, F., 2017. Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis. Frontiers in Aging Neuroscience 9.
Hu, Y.Y., He, S.S., Wang, X., Duan, Q.H., Grundke-Iqbal, I., Iqbal, K., Wang, J., 2002. Levels of Nonphosphorylated and Phosphorylated Tau in Cerebrospinal Fluid of Alzheimer’s Disease Patients : An Ultrasensitive Bienzyme-Substrate-Recycle Enzyme-Linked Immunosorbent Assay. The American Journal of Pathology 160, 1269-1278.
Kenessey, A., Yen, S.H., 1993. The extent of phosphorylation of fetal tau is comparable to that of PHF-tau from Alzheimer paired helical filaments. Brain research 629, 40-46.
Kim, S.Y., Kim, J.K., Park, S.H., Kim, B.G., Jang, A.S., Oh, S.H., Lee, J.H., Suh, M.W., Park, M.K., 2018. Effects of inhaled particulate matter on the central nervous system in mice. Neurotoxicology 67, 169-177.
Kimura, T., Ono, T., Takamatsu, J., Yamamoto, H., Ikegami, K., Kondo, A., Hasegawa, M., Ihara, Y., Miyamoto, E., Miyakawa, T., 1996. Sequential changes of tau-site-specific phosphorylation during development of paired helical filaments. Dementia (Basel, Switzerland) 7, 177-181.
Kodavanti, U.P., Schladweiler, M.C., Ledbetter, A.D., Watkinson, W.P., Campen, M.J., Winsett, D.W., Richards, J.R., Crissman, K.M., Hatch, G.E., Costa, D.L., 2000. The spontaneously hypertensive rat as a model of human cardiovascular disease: evidence of exacerbated cardiopulmonary injury and oxidative stress from inhaled emission particulate matter. Toxicology and applied pharmacology 164, 250-263.
Kopke, E., Tung, Y.C., Shaikh, S., Alonso, A.C., Iqbal, K., Grundke-Iqbal, I., 1993. Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. The Journal of biological chemistry 268, 24374-24384.
Koulova, A., Frishman, W.H., 2014. Air pollution exposure as a risk factor for cardiovascular disease morbidity and mortality. Cardiology in review 22, 30-36.
Kren, V., Pravenec, M., Lu, S., Krenova, D., Wang, J.M., Wang, N., Merriouns, T., Wong, A., St Lezin, E., Lau, D., Szpirer, C., Szpirer, J., Kurtz, T.W., 1997. Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat. The Journal of clinical investigation 99, 577-581.
Ksiezak-Reding, H., Liu, W.K., Yen, S.H., 1992. Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments. Brain research 597, 209-219.
Kunzli, N., Jerrett, M., Mack, W.J., Beckerman, B., LaBree, L., Gilliland, F., Thomas, D., Peters, J., Hodis, H.N., 2005. Ambient air pollution and atherosclerosis in Los Angeles. Environmental health perspectives 113, 201-206.
Lachen-Montes, M., Gonzalez-Morales, A., de Morentin, X.M., Perez-Valderrama, E., Ausin, K., Zelaya, M.V., Serna, A., Aso, E., Ferrer, I., Fernandez-Irigoyen, J., Santamaria, E., 2016. An early dysregulation of FAK and MEK/ERK signaling pathways precedes the beta-amyloid deposition in the olfactory bulb of APP/PS1 mouse model of Alzheimer''s disease. Journal of proteomics 148, 149-158.
Levesque, S., Surace, M.J., McDonald, J., Block, M.L., 2011a. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease. Journal of neuroinflammation 8, 105.
Levesque, S., Taetzsch, T., Lull, M.E., Kodavanti, U., Stadler, K., Wagner, A., Johnson, J.A., Duke, L., Kodavanti, P., Surace, M.J., Block, M.L., 2011b. Diesel exhaust activates and primes microglia: air pollution, neuroinflammation, and regulation of dopaminergic neurotoxicity. Environmental health perspectives 119, 1149-1155.
Liu, Z., Li, T., Li, P., Wei, N., Zhao, Z., Liang, H., Ji, X., Chen, W., Xue, M., Wei, J., 2015. The Ambiguous Relationship of Oxidative Stress, Tau Hyperphosphorylation, and Autophagy Dysfunction in Alzheimer''s Disease. Oxidative medicine and cellular longevity 2015, 352723.
Matsuo, E.S., Shin, R.W., Billingsley, M.L., Van deVoorde, A., O''Connor, M., Trojanowski, J.Q., Lee, V.M., 1994. Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer''s disease paired helical filament tau. Neuron 13, 989-1002.
Maurage, C.A., Sergeant, N., Ruchoux, M.M., Hauw, J.J., Delacourte, A., 2003. Phosphorylated serine 199 of microtubule-associated protein tau is a neuronal epitope abundantly expressed in youth and an early marker of tau pathology. Acta neuropathologica 105, 89-97.
McGeer, P.L., McGeer, E.G., 2007. NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiology of aging 28, 639-647.
Metcalfe, M.J., Figueiredo-Pereira, M.E., 2010. Relationship between tau pathology and neuroinflammation in Alzheimer''s disease. The Mount Sinai journal of medicine, New York 77, 50-58.
Mills, N.L., Donaldson, K., Hadoke, P.W., Boon, N.A., MacNee, W., Cassee, F.R., Sandstrom, T., Blomberg, A., Newby, D.E., 2009. Adverse cardiovascular effects of air pollution. Nature clinical practice Cardiovascular medicine 6, 36-44.
Mondon, C.E., Reaven, G.M., 1988. Evidence of abnormalities of insulin metabolism in rats with spontaneous hypertension. Metabolism: clinical and experimental 37, 303-305.
Mondragon-Rodriguez, S., Perry, G., Zhu, X., Moreira, P.I., Acevedo-Aquino, M.C., Williams, S., 2013. Phosphorylation of tau protein as the link between oxidative stress, mitochondrial dysfunction, and connectivity failure: implications for Alzheimer''s disease. Oxidative medicine and cellular longevity 2013, 940603.
Nelin, T.D., Joseph, A.M., Gorr, M.W., Wold, L.E., 2012. Direct and indirect effects of particulate matter on the cardiovascular system. Toxicology letters 208, 293-299.
Oberdorster, G., Oberdorster, E., Oberdorster, J., 2005. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environmental health perspectives 113, 823-839.
Oberdorster, G., Sharp, Z., Atudorei, V., Elder, A., Gelein, R., Kreyling, W., Cox, C., 2004. Translocation of inhaled ultrafine particles to the brain. Inhalation toxicology 16, 437-445.
Okamoto, K., Aoki, K., 1963. Development of a strain of spontaneously hypertensive rats. Japanese circulation journal 27, 282-293.
Perez, C.M., Hazari, M.S., Farraj, A.K., 2015. Role of autonomic reflex arcs in cardiovascular responses to air pollution exposure. Cardiovascular toxicology 15, 69-78.
Peric, A., Annaert, W., 2015. Early etiology of Alzheimer''s disease: tipping the balance toward autophagy or endosomal dysfunction? Acta neuropathologica 129, 363-381.
Peters, A., Pope, C.A., 3rd, 2002. Cardiopulmonary mortality and air pollution. Lancet (London, England) 360, 1184-1185.
Pilz, J., Meineke, I., Gleiter, C.H., 2000. Measurement of free and bound malondialdehyde in plasma by high-performance liquid chromatography as the 2, 4-dinitrophenylhydrazine derivative. Journal of Chromatography B: Biomedical Sciences and Applications 742, 315-325.
Pinto, Y.M., Paul, M., Ganten, D., 1998. Lessons from rat models of hypertension: from Goldblatt to genetic engineering. Cardiovascular research 39, 77-88.
Pope, C.A., 3rd, Burnett, R.T., Thurston, G.D., Thun, M.J., Calle, E.E., Krewski, D., Godleski, J.J., 2004. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation 109, 71-77.
Ranft, U., Schikowski, T., Sugiri, D., Krutmann, J., Kramer, U., 2009. Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly. Environmental research 109, 1004-1011.
Saldiva, P.H., Clarke, R.W., Coull, B.A., Stearns, R.C., Lawrence, J., Murthy, G.G., Diaz, E., Koutrakis, P., Suh, H., Tsuda, A., Godleski, J.J., 2002. Lung inflammation induced by concentrated ambient air particles is related to particle composition. American journal of respiratory and critical care medicine 165, 1610-1617.
Schoenfeld, T.A., Obar, R.A., 1994. Diverse distribution and function of fibrous microtubule-associated proteins in the nervous system. International review of cytology 151, 67-137.
Selkoe, D.J., 2001. Alzheimer''s disease: genes, proteins, and therapy. Physiological reviews 81, 741-766.
Seubert, P., Mawal-Dewan, M., Barbour, R., Jakes, R., Goedert, M., Johnson, G.V., Litersky, J.M., Schenk, D., Lieberburg, I., Trojanowski, J.Q., et al., 1995. Detection of phosphorylated Ser262 in fetal tau, adult tau, and paired helical filament tau. The Journal of biological chemistry 270, 18917-18922.
Shackelford, C., Long, G., Wolf, J., Okerberg, C., Herbert, R., 2002. Qualitative and quantitative analysis of nonneoplastic lesions in toxicology studies. Toxicologic pathology 30, 93-96.
Shimada, A., Kawamura, N., Okajima, M., Kaewamatawong, T., Inoue, H., Morita, T., 2006. Translocation pathway of the intratracheally instilled ultrafine particles from the lung into the blood circulation in the mouse. Toxicologic pathology 34, 949-957.
Simkhovich, B.Z., Kleinman, M.T., Kloner, R.A., 2008. Air pollution and cardiovascular injury epidemiology, toxicology, and mechanisms. Journal of the American College of Cardiology 52, 719-726.
Smith, M.A., Rottkamp, C.A., Nunomura, A., Raina, A.K., Perry, G., 2000. Oxidative stress in Alzheimer''s disease. Biochimica et biophysica acta 1502, 139-144.
Soderberg, M., Edlund, C., Kristensson, K., Dallner, G., 1991. Fatty acid composition of brain phospholipids in aging and in Alzheimer''s disease. Lipids 26, 421-425.
Suglia, S.F., Gryparis, A., Wright, R.O., Schwartz, J., Wright, R.J., 2008. Association of black carbon with cognition among children in a prospective birth cohort study. American journal of epidemiology 167, 280-286.
Tamagawa, E., van Eeden, S.F., 2006. Impaired lung function and risk for stroke: role of the systemic inflammation response? Chest 130, 1631-1633.
Tatebayashi, Y., Haque, N., Tung, Y.C., Iqbal, K., Grundke-Iqbal, I., 2004. Role of tau phosphorylation by glycogen synthase kinase-3beta in the regulation of organelle transport. Journal of cell science 117, 1653-1663.
Trojanowski, J.Q., Lee, V.M., 1995. Phosphorylation of paired helical filament tau in Alzheimer''s disease neurofibrillary lesions: focusing on phosphatases. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9, 1570-1576.
Tukozkan, N., Erdamar, H., Seven, I., 2006. Measurement of total malondialdehyde in plasma and tissues by high-performance liquid chromatography and thiobarbituric acid assay. Firat Tip Dergisi 11, 88-92.
Upadhyay, S., Stoeger, T., George, L., Schladweiler, M.C., Kodavanti, U., Ganguly, K., Schulz, H., 2014. Ultrafine carbon particle mediated cardiovascular impairment of aged spontaneously hypertensive rats. Particle and fibre toxicology 11.
van Berlo, D., Albrecht, C., Knaapen, A.M., Cassee, F.R., Gerlofs-Nijland, M.E., Kooter, I.M., Palomero-Gallagher, N., Bidmon, H.J., van Schooten, F.J., Krutmann, J., Schins, R.P., 2010. Comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain. Archives of toxicology 84, 553-562.
Verwilst, P., Kim, H.S., Kim, S., Kang, C., Kim, J.S., 2018. Shedding light on tau protein aggregation: the progress in developing highly selective fluorophores. Chemical Society reviews 47, 2249-2265.
Wang, Y., Mandelkow, E., 2012. Degradation of tau protein by autophagy and proteasomal pathways. Biochemical Society transactions 40, 644-652.
Wang, Y., Xiong, L., Tang, M., 2017. Toxicity of inhaled particulate matter on the central nervous system: neuroinflammation, neuropsychological effects and neurodegenerative disease. Journal of applied toxicology : JAT 37, 644-667.
Watkinson, W.P., Campen, M.J., Nolan, J.P., Costa, D.L., 2001. Cardiovascular and systemic responses to inhaled pollutants in rodents: effects of ozone and particulate matter. Environmental health perspectives 109 Suppl 4, 539-546.
Weingarten, M.D., Lockwood, A.H., Hwo, S.Y., Kirschner, M.W., 1975. A protein factor essential for microtubule assembly. Proceedings of the National Academy of Sciences of the United States of America 72, 1858-1862.
Wichers, L.B., Nolan, J.P., Winsett, D.W., Ledbetter, A.D., Kodavanti, U.P., Schladweiler, M.C., Costa, D.L., Watkinson, W.P., 2004a. Effects of instilled combustion-derived particles in spontaneously hypertensive rats. Part I: Cardiovascular responses. Inhalation toxicology 16, 391-405.
Wichers, L.B., Nolan, J.P., Winsett, D.W., Ledbetter, A.D., Kodavanti, U.P., Schladweiler, M.C., Costa, D.L., Watkinson, W.P., 2004b. Effects of instilled combustion-derived particles in spontaneously hypertensive rats. Part II: Pulmonary responses. Inhalation toxicology 16, 407-419.
Win-Shwe, T.T., Fujimaki, H., Fujitani, Y., Hirano, S., 2012a. Novel object recognition ability in female mice following exposure to nanoparticle-rich diesel exhaust. Toxicology and applied pharmacology 262, 355-362.
Win-Shwe, T.T., Yamamoto, S., Fujitani, Y., Hirano, S., Fujimaki, H., 2012b. Nanoparticle-rich diesel exhaust affects hippocampal-dependent spatial learning and NMDA receptor subunit expression in female mice. Nanotoxicology 6, 543-553.
Wu, Y.-L., 2016. CNS toxicity induced by DEPs and ambient particles.
Yan, Y.H., C, C.K.C., Wang, J.S., Tung, C.L., Li, Y.R., Lo, K., Cheng, T.J., 2014. 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 281, 211-220.
Ying, Z., Xie, X., Bai, Y., Chen, M., Wang, X., Zhang, X., Morishita, M., Sun, Q., Rajagopalan, S., 2015. Exposure to concentrated ambient particulate matter induces reversible increase of heart weight in spontaneously hypertensive rats. Particle and fibre toxicology 12, 15.
Yoshida, H., Ihara, Y., 1993. Tau in paired helical filaments is functionally distinct from fetal tau: assembly incompetence of paired helical filament-tau. Journal of neurochemistry 61, 1183-1186.
Young, I.S., Trimble, E.R., 1991. Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection. Annals of clinical biochemistry 28 ( Pt 5), 504-508.
Zanchi, A.C., Fagundes, L.S., Barbosa, F., Jr., Bernardi, R., Rhoden, C.R., Saldiva, P.H., do Valle, A.C., 2010a. Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress. Inhalation toxicology 22, 910-918.
Zanchi, A.C., Saiki, M., Saldiva, P.H., Barros, H.M., Rhoden, C.R., 2010b. Hippocampus lipid peroxidation induced by residual oil fly ash intranasal instillation versus habituation to the open field. Inhalation toxicology 22, 84-88.
Zanchi, A.C., Venturini, C.D., Saiki, M., Nascimento Saldiva, P.H., Tannhauser Barros, H.M., Rhoden, C.R., 2008. Chronic nasal instillation of residual-oil fly ash (ROFA) induces brain lipid peroxidation and behavioral changes in rats. Inhalation toxicology 20, 795-800.
Zelaya, M.V., Perez-Valderrama, E., de Morentin, X.M., Tunon, T., Ferrer, I., Luquin, M.R., Fernandez-Irigoyen, J., Santamaria, E., 2015. Olfactory bulb proteome dynamics during the progression of sporadic Alzheimer''s disease: identification of common and distinct olfactory targets across Alzheimer-related co-pathologies. Oncotarget 6, 39437-39456.
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