本文選題：甲醛 + 認(rèn)知　； 參考：《陜西師范大學(xué)》2016年博士論文

【摘要】：甲醛(Formaldehyde)是醛族分子結(jié)構(gòu)最簡(jiǎn)單而且易揮發(fā)的有機(jī)化合物之一,在自然界中廣泛存在,由于甲醛是一種活性較強(qiáng)的有機(jī)物而且比較廉價(jià),所以廣泛應(yīng)用于各個(gè)領(lǐng)域并且在工業(yè)上有很重要的作用,主要應(yīng)用于建筑材料、人造板、涂料等建筑材料中。目前,甲醛已經(jīng)成為一種常見的室內(nèi)空氣污染物,在住宅和建筑中都能獲得相對(duì)較高的濃度。這種甲醛污染主要是由于人造涂料和油漆的應(yīng)用所引起的,而且甲醛很容易通過(guò)血-腦屏障,最終在人體內(nèi)蓄積,并有可能影響大腦中的神經(jīng)膠質(zhì)細(xì)胞和神經(jīng)細(xì)胞。研究表明,甲醛是有毒的,它的毒性主要表現(xiàn)在可引起過(guò)敏和致癌,而對(duì)于過(guò)敏人群來(lái)說(shuō),主要是建議遠(yuǎn)離有甲醛的地方,而且長(zhǎng)期接觸甲醛可引起胃腸道問(wèn)題,頭痛和記憶力減退等癥狀。動(dòng)物研究表明,吸入甲醛暴露可引起活動(dòng)性的降低和學(xué)習(xí)記憶能力的損傷,表明有明顯的神經(jīng)系統(tǒng)毒性。而這些研究主要是集中在環(huán)境管理和流行病學(xué)的研究,但是甲醛引起的潛在的神經(jīng)毒性機(jī)制研究的較少。研究表明,吸入甲醛暴露或海馬內(nèi)注射甲醛導(dǎo)致動(dòng)物在水迷宮中的空間學(xué)習(xí)和記憶的損傷,這種損傷是和腦內(nèi)降低的超氧化物歧化酶(SOD)的活性,丙二醛(MDA)含量的減少及腦中DNA轉(zhuǎn)錄的穩(wěn)態(tài)失調(diào)以及降低的腦內(nèi)NR1,NR2B mRNA的表達(dá)有關(guān)。海馬是參與空間學(xué)習(xí)記憶最主要的腦區(qū),但是損傷海馬的機(jī)制還不清楚。文獻(xiàn)報(bào)道,急性甲醛暴露在5ppm會(huì)降低大鼠的運(yùn)動(dòng)能力,而且為期一周的甲醛吸入會(huì)增加雄性小鼠的抑郁樣行為,然而研究表明,甲醛對(duì)小鼠的活動(dòng)性的影響具有兩性差異,那么長(zhǎng)期的甲醛暴露是否會(huì)產(chǎn)生焦慮和抑郁樣行為以及這些行為的影響是否存在兩性差異,還不清楚,也未見相關(guān)報(bào)道。甲醛暴露會(huì)影響動(dòng)物在水迷宮中的空間學(xué)習(xí)記憶和新物體識(shí)別能力,水迷宮實(shí)驗(yàn)主要是檢驗(yàn)動(dòng)物在水迷宮你中找到隱性平臺(tái)的能力,新物體識(shí)別主要是檢測(cè)動(dòng)物對(duì)物體位置的記憶和區(qū)別不同形狀物體的能力,而社會(huì)識(shí)別不同于水迷宮實(shí)驗(yàn)和心物體識(shí)別實(shí)驗(yàn),它是檢測(cè)動(dòng)物識(shí)別和記憶同種其它個(gè)體的能力,但是甲醛暴露是否會(huì)損傷社會(huì)識(shí)別能力,還不清楚。神經(jīng)遞質(zhì)多巴胺和谷氨酸N-甲基-D-天冬氨酸(NMDA)受體亞型在腦功能方面起著非常重要的作用。海馬和杏仁核內(nèi)含有大量的NMDA受體和多巴胺受體,這些核團(tuán)(海馬和杏仁核)在情緒和認(rèn)知方面發(fā)揮著非常重要的作用。研究表明,甲醛暴露可以降低大鼠的活動(dòng)性,增加前額葉皮質(zhì)的多巴胺水平。表明甲醛暴露與多巴胺的變化有關(guān)。而且研究也表明,甲醛暴露降低了小鼠腦內(nèi)NRlmRNA的表達(dá)水平。但是甲醛暴露對(duì)情緒和認(rèn)知的影響是否與DA系統(tǒng)和NMDA相關(guān),還沒有這方面的研究。在本研究中我們探討了吸入甲醛暴露對(duì)Morris水迷宮實(shí)驗(yàn)的影響以及相關(guān)的神經(jīng)生物學(xué)機(jī)制。并且研究了甲醛暴露對(duì)焦慮、抑郁樣行為和社會(huì)識(shí)別的影響以及與這些影響有關(guān)的多巴胺D1型受體和D2型受體以及NR1的基因表達(dá)的變化。母親-嬰兒的相互作用是導(dǎo)致行為長(zhǎng)期變化的關(guān)鍵。產(chǎn)后應(yīng)激或某些化學(xué)暴露能改變泌乳期雌性對(duì)幼仔的照顧行為,而且也會(huì)影響幼仔的發(fā)育。有研究報(bào)道,甲醛暴露可以引起雌性小鼠體內(nèi)雌激素水平的變化,另有文獻(xiàn)表明,甲醛也是一種化學(xué)應(yīng)激物,是否吸入甲醛暴露能改變母本行為,也未見相關(guān)報(bào)道。甲醛吸入暴露是否能改變母本行為,并且對(duì)動(dòng)物以后的腦發(fā)育和行為產(chǎn)生影響也未見相關(guān)報(bào)道。因此,我們還研究了吸入甲醛暴露對(duì)產(chǎn)后母本行為的影響及產(chǎn)后暴露甲醛對(duì)成年小鼠腦發(fā)育和行為的影響。(1)甲醛暴露對(duì)小鼠空間學(xué)習(xí)記憶的影響及對(duì)海馬內(nèi)糖皮質(zhì)激素和血清中皮質(zhì)酮的影響的研究表明,2ppm甲醛吸入組的小鼠在水迷宮中游到平臺(tái)的潛伏期和花費(fèi)在水迷宮中的貼壁時(shí)間顯著延長(zhǎng)。在記憶保留期,2ppm甲醛組的小鼠找到隱性平臺(tái)的潛伏期和錯(cuò)誤次數(shù)顯著增加,這些行為實(shí)驗(yàn)研究結(jié)果都說(shuō)明吸入甲醛損傷了小鼠在水迷宮中的空間學(xué)習(xí)記憶能力,并且沒有顯著的兩性差異。免疫組織化學(xué)實(shí)驗(yàn)結(jié)果表明,2ppm甲醛組的小鼠海馬中糖皮質(zhì)激素受體的陽(yáng)性神經(jīng)元的表達(dá)在海馬CA1區(qū)和CA3區(qū)都有很顯著性的降低;Western blot實(shí)驗(yàn)結(jié)果顯示,吸入2ppmn濃度甲醛的小鼠降低了海馬內(nèi)糖皮質(zhì)激素受體的表達(dá)量;而且酶聯(lián)免疫實(shí)驗(yàn)結(jié)果也表明,小鼠吸入2ppm濃度的甲醛顯著性的提高了血清中的糖皮質(zhì)激素的水平。這些實(shí)驗(yàn)結(jié)果都表明,高濃度(2ppm)的甲醛暴露損傷了小鼠對(duì)空間學(xué)習(xí)記憶,而且這種損傷可能是由于甲醛暴露引起皮質(zhì)酮的改變而引起海馬內(nèi)糖皮質(zhì)激素受體水平的改變,從而損傷了小鼠的空間學(xué)習(xí)記憶能力。(2)甲醛暴露對(duì)小鼠焦慮、抑郁行為和社會(huì)識(shí)別的影響及相關(guān)內(nèi)分泌機(jī)制的研究中發(fā)現(xiàn),吸入甲醛暴露在2ppm組的雌雄小鼠都降低了活動(dòng)性,降低了兩性在曠場(chǎng)中心場(chǎng)所呆的時(shí)間百分比,并且表現(xiàn)出顯著的兩性差異。在高架試驗(yàn)檢測(cè)中,甲醛處理很明顯降低了活動(dòng)性,穿越開臂的次數(shù)和穿越開臂的時(shí)間,并且這種影響表現(xiàn)出明顯的兩性差異。在強(qiáng)迫游泳實(shí)驗(yàn)中發(fā)現(xiàn),甲醛暴露很明顯增加了兩性在水中的不動(dòng)時(shí)間,而且甲醛處理表現(xiàn)出很明顯的兩性差異。這些行為實(shí)驗(yàn)結(jié)果表明,甲醛暴露產(chǎn)生了很嚴(yán)重的焦慮和抑郁樣行為。在社會(huì)識(shí)別實(shí)驗(yàn)中,甲醛暴露降低了兩性(雌雄)小鼠對(duì)刺激鼠的探究時(shí)間;吸入2ppm甲醛組的小鼠在習(xí)慣化和去習(xí)慣化實(shí)驗(yàn)中,并不能識(shí)別熟悉鼠和陌生鼠,并且與對(duì)照組相比,2ppm甲醛組的小鼠很明顯降低了對(duì)刺激鼠的探究時(shí)間,表明損傷了社會(huì)識(shí)別能力。用實(shí)時(shí)定量PCR分析顯示,與對(duì)照組相比,2ppm甲醛暴露上調(diào)了海馬D1RmRNA和D2RmRNA的表達(dá),而在杏仁核,上調(diào)了 D1RmRNA,降低了 D2RmRNA的水平;2ppm甲醛處理組的小鼠下調(diào)了海馬和杏仁核中谷氨酸N-甲基-D-天冬氨酸I型受體(NR1)mRNA的表達(dá)。然而,在0.4ppm甲醛暴露組沒有出現(xiàn)這些影響。這些結(jié)果說(shuō)明甲醛對(duì)行為和神經(jīng)內(nèi)分泌參數(shù)的的影響具有劑量依賴性。(3)我們研究了幼仔在出生后1-6天的母本行為的研究結(jié)果表明,產(chǎn)后吸入甲醛對(duì)泌乳期的雌性的母本行為沒有顯著的影響。只是甲醛暴露在0.4ppm組的小鼠在第五天時(shí)活動(dòng)性顯著增加。產(chǎn)后吸入甲醛對(duì)泌乳期的雌性的母本行為沒有顯著的影響。但是出生后甲醛暴露在0.4ppm組減少了在曠場(chǎng)中心場(chǎng)和高架開臂所呆的時(shí)間,表明出生后甲醛暴露增加了成年后的焦慮樣行為,0.4ppm組雌雄小鼠和0.08ppm組雄性小鼠增加了在水迷宮中的不動(dòng)時(shí)間,表明增加了抑郁樣行為。實(shí)時(shí)定量分析表明,出生后甲醛暴露增加了海馬D1RmRNA的表達(dá),降低了 NRlmRNA在海馬的表達(dá)。這些結(jié)果表明出生后甲醛暴露沒有改變母本行為,但是增加了幼仔在成年后的焦慮和抑郁水平,改變海馬內(nèi)D1R和NRlmRNA的表達(dá),說(shuō)明甲醛暴露可能直接作用于幼仔而影響了幼仔的腦和行為的發(fā)育。通過(guò)這些研究結(jié)果,我們可以得出結(jié)論,吸入甲醛暴露對(duì)情緒和認(rèn)知都產(chǎn)生顯著影響,這些行為的改變和認(rèn)知的損傷是和海馬內(nèi)的糖皮質(zhì)激素水平、多巴胺系統(tǒng)和NMDA的改變有關(guān)。這些研究也表明,甲醛可以引起多方面的的神經(jīng)毒性。產(chǎn)后暴露甲醛沒有改變母本行為,卻改變了后代成年后腦和行為的發(fā)育,表明甲醛可能是直接作用于小鼠幼仔從而影響成年行為和神經(jīng)內(nèi)分泌系統(tǒng)的發(fā)育。這些結(jié)論說(shuō)明,不同時(shí)期甲醛暴露都可能會(huì)影響動(dòng)物的行為和大腦的神經(jīng)可塑性,同時(shí)也為甲醛的生態(tài)風(fēng)險(xiǎn)、健康評(píng)估以及甲醛的污染監(jiān)測(cè)和控制標(biāo)準(zhǔn)的制訂提供參考。
[Abstract]:Formaldehyde (Formaldehyde) is one of the simplest and volatile organic compounds of the aldehyde group. It exists widely in nature. As formaldehyde is a kind of strong organic substance and cheap, it is widely used in various fields and has very important role in industry. It is mainly used in building materials, wood-based panels, and coatings. At present, formaldehyde has become a common indoor air pollutant, which can obtain relatively high concentration in both houses and buildings. This formaldehyde pollution is mainly caused by the application of artificial coatings and paints, and formaldehyde is easily accumulated through blood - brain barrier and eventually accumulates in the human body, and may affect big Neuroglia and nerve cells in the brain. Studies have shown that formaldehyde is toxic and its toxicity is mainly caused by allergies and carcinogens, and for allergic populations, it is mainly recommended to stay away from formaldehyde, and long-term exposure to formaldehyde can cause gastrointestinal problems, headache and memory impairment. Animal studies have shown that Exposure to inhaled formaldehyde can cause a decrease in activity and impairment of learning and memory ability, indicating a significant neurotoxicity. These studies are mainly focused on environmental management and epidemiological studies, but the underlying neurotoxicity mechanism caused by formaldehyde is less. Aldehydes cause damage to space learning and memory in the water maze of animals, such as the activity of superoxide dismutase (SOD), the decrease of the content of malondialdehyde (MDA) and the homeostasis of DNA transcription in the brain, and the reduced expression of NR1 in the brain, and the expression of NR2B mRNA. The hippocampus is the most important brain area involved in spatial learning and memory. But the mechanism for damaging the hippocampus is not clear. It is reported that exposure to acute formaldehyde in 5ppm can reduce the exercise ability of rats, and a week of formaldehyde inhalation will increase the depressive behavior of male mice. However, the study shows that formaldehyde has a two sex difference in the effect of the activity of mice, then whether long-term formaldehyde exposure will be produced. It is not clear that there is a gender difference between the behavior of anxiety and depression and the effects of these behaviors. It is not clear, and no related reports. Formaldehyde exposure affects the spatial learning and memory of animals and the ability to recognize new objects in the water maze. The water maze experiment is mainly to test the ability of the animals to find the hidden platform in the water maze. It is different from the water maze test and the heart object recognition experiment to detect the memory of the animal's location and the ability to distinguish the different shapes of objects. It is the ability to detect and memory the other individuals of the same species, but it is not clear whether the formaldehyde exposure can damage the social recognition ability. It is not clear that neurotransmitter dopamine and glutamine can be found. The acid N- methyl -D- aspartic acid (NMDA) receptor subtype plays a very important role in brain function. The hippocampus and amygdala contain a large number of NMDA receptors and dopamine receptors. These nuclei (hippocampus and amygdala) play a very important role in emotional and cognitive aspects. The level of dopamine in the prefrontal cortex was increased. It showed that exposure to formaldehyde was associated with changes in dopamine. Moreover, the study also showed that exposure to formaldehyde decreased the level of NRlmRNA expression in the brain of mice. However, the effects of formaldehyde exposure on emotion and cognition were related to the DA system and NMDA, and there was no study in this field. The effects of exposure to formaldehyde exposure on the Morris water maze experiment and related neurobiological mechanisms. And the effects of formaldehyde exposure on anxiety, depressive behavior and social recognition, and the changes in the D1 receptor and D2 receptor as well as the gene expression of NR1 related to these effects. The key to long-term changes in behavior. Postpartum stress or some chemical exposure can change the behavior of the female in lactation, and also affect the development of the young. Exposure can change maternal behavior and no related reports. Whether formaldehyde inhalation exposure can change maternal behavior and effect on brain development and behavior in animals has not been reported. Therefore, we also studied the effects of inhaled formaldehyde exposure on maternal behavior and postpartum exposure to brain development and behavior in adult mice. (1) the effects of formaldehyde exposure on the spatial learning and memory of mice and the effects on corticosteroids and serum corticosterone in the hippocampus showed that the incubation period of the 2ppm formaldehyde inhalation group in the water maze and the time spent in the water maze were significantly longer. In the memory retention period, the mice in the 2ppm formaldehyde group were in the mice. The incubation period and the number of errors found in the recessive platform increased significantly. The results of these behavioral experiments showed that inhaled formaldehyde had damaged the spatial learning and memory ability of mice in the water maze, and there was no significant gender difference. The results of immunohistochemistry showed that the glucocorticoid receptor in the hippocampus of the 2ppm formaldehyde group was positive. The expression of neurons in the hippocampal CA1 region and CA3 region decreased significantly; the Western blot test showed that the mice inhaled 2ppmn with formaldehyde decreased the expression of glucocorticoid receptor in the hippocampus, and the enzyme linked immunosorbent assay also showed that the concentration of formaldehyde in the mice inhaled 2ppm increased the sugar cortex in the serum. The level of hormone. These results show that high concentration (2ppm) exposure to formaldehyde can damage the learning and memory of mice, and this damage may be caused by changes in corticosterone induced by formaldehyde exposure, causing changes in the level of glucocorticoid receptor in the hippocampus, thereby damaging the learning and memory ability of mice. (2) exposure to formaldehyde. In the study of the influence of mouse anxiety, depression behavior and social recognition and related endocrine mechanisms, it was found that the female and male mice exposed to formaldehyde in the 2ppm group reduced the activity, reduced the percentage of the sex in the center of the open field, and showed a significant difference in two. In the elevated test, the formaldehyde treatment was very clear. The activity, the number of times of crossing the arm and the time of crossing the arm, and the effect showed obvious gender differences. In the forced swimming test, it was found that formaldehyde exposure significantly increased the time of the amphoteric in the water, and the formaldehyde treatment showed a distinct gender difference. In the social identification experiment, the exposure to formaldehyde decreased the study time of the sexes (male and female) in the mice, and the mice inhaled in the 2ppm formaldehyde group did not recognize both the familiar and the unfamiliar mice in the customary and deformable experiments, and compared with the control group, the mice of the 2ppm formaldehyde group were very good. Compared with the control group, 2ppm formaldehyde exposure up-regulated the expression of D1RmRNA and D2RmRNA in the hippocampus compared with the control group, while in the amygdala, D1RmRNA was up and D2RmRNA was lowered in the amygdala, and the mice of the 2ppm formaldehyde treatment group lowered the hippocampus and amygdala in the 2ppm formaldehyde treatment group, compared with the control group. The expression of I type I receptor (NR1) mRNA of the glutamic acid N- methyl -D- aspartic acid in the nucleus, however, did not appear in the 0.4ppm formaldehyde exposure group. These results suggest that the effects of formaldehyde on behavioral and neuroendocrine parameters are dose-dependent. (3) we studied the results of maternal behavior at 1-6 days after birth. Formaldehyde inhalation did not significantly affect female parent behavior during the lactation period. Only the mice exposed to formaldehyde in the 0.4ppm group increased significantly at fifth days. The time of opening the arm showed that the exposure to formaldehyde increased the anxiety like behavior after birth. In group 0.4ppm, male and male mice and 0.08ppm male mice increased the time of immobility in the water maze, indicating an increase in depressive behavior. Real time quantitative analysis showed that after birth, formaldehyde exposure increased the expression of D1RmRNA in the hippocampus and reduced the NRlmRNA. Expression in the hippocampus. These results suggest that postnatal exposure to formaldehyde does not change maternal behavior, but increases the level of anxiety and depression in young adults, changes the expression of D1R and NRlmRNA in the hippocampus, indicating that exposure to formaldehyde may directly affect young children and affect the development of the brain and behavior of young children. It can be concluded that exposure to formaldehyde exposure has a significant effect on emotion and cognition. Changes in these behaviors and cognitive impairment are associated with levels of glucocorticoid in the hippocampus, the dopamine system and the changes in NMDA. These studies also suggest that formaldehyde can cause multiple neurotoxicity. Postpartum exposure to formaldehyde does not change maternal parents. Behavior, which changes the development of the brain and behavior of the offspring, indicates that formaldehyde may affect the adult behavior and the development of the neuroendocrine system. These conclusions suggest that exposure to formaldehyde in different periods may affect the behavior of the animals and the plasticity of the brain, and also the ecological risk of formaldehyde. It provides reference for health assessment and formaldehyde pollution monitoring and control standards.
【學(xué)位授予單位】：陜西師范大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R114

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 廖雙;蔣莉;張曉萍;;腦發(fā)育不同階段甲醛暴露對(duì)大鼠學(xué)習(xí)記憶能力及海馬CA3區(qū)CaMKⅡ表達(dá)的影響[J];重慶醫(yī)科大學(xué)學(xué)報(bào);2010年03期

2 王小玲;原福勝;張志紅;白劍英;趙五紅;梁瑞峰;;甲醛吸入對(duì)小鼠學(xué)習(xí)記憶能力的影響[J];環(huán)境與健康雜志;2008年05期

3 周黨俠;邱曙東;張潔;王志勇;;甲醛對(duì)性成熟期雄性大鼠生殖毒性的作用研究[J];四川大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2006年04期

4 于立群,蔣守芳,冷曙光,張春之,閻永建,牛勇,張艷淑,何鳳生,鄭玉新;甲醛暴露工人外周血淋巴細(xì)胞遺傳物質(zhì)損傷水平的研究[J];中華預(yù)防醫(yī)學(xué)雜志;2005年06期

5 劉素香,郭四紅;甲醛對(duì)作業(yè)工人健康影響的調(diào)查分析[J];職業(yè)衛(wèi)生與應(yīng)急救援;2004年02期

6 王偉,唐明德,易義珍,謝穎;甲醛對(duì)雌性小鼠動(dòng)情周期及卵巢的影響[J];實(shí)用預(yù)防醫(yī)學(xué);2002年06期

7 封永康，王維，姜宗箕，胡剛，鐘善華，，張華;甲醛對(duì)作業(yè)工人職業(yè)危害的調(diào)查[J];安徽預(yù)防醫(yī)學(xué)雜志;1996年02期

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