發(fā)布時(shí)間：2018-09-08 17:14

【摘要】：重復(fù)經(jīng)顱磁刺激（rTMS）是一種無(wú)損傷、無(wú)侵入性的物理治療方法，目前已逐漸得到人們關(guān)注。研究報(bào)道rTMS可以提高正常老化和阿爾茲海默�。ˋD）患者的認(rèn)知功能損傷。rTMS對(duì)認(rèn)知功能的改善是通過(guò)網(wǎng)絡(luò)化，多通路調(diào)節(jié)腦組織結(jié)構(gòu)和功能發(fā)揮作用的。研究報(bào)道，rTMS作用于神經(jīng)系統(tǒng)可以提高神經(jīng)元的興奮性，并增加突觸可塑性。rTMS改善突觸可塑性的效應(yīng)可以表現(xiàn)為長(zhǎng)時(shí)程增強(qiáng)（LTP）效應(yīng)。動(dòng)物實(shí)驗(yàn)證明，在應(yīng)用高頻rTMS改善動(dòng)物認(rèn)知功能的同時(shí)，所記錄到的海馬腦片LTP顯著增強(qiáng)了。在基因水平、蛋白質(zhì)水平、代謝產(chǎn)物水平的研究表明，rTMS可以通過(guò)調(diào)節(jié)改善神經(jīng)元可塑性相關(guān)基因、蛋白的表達(dá)和代謝產(chǎn)物平衡保護(hù)神經(jīng)元。然而，高頻rTMS改善認(rèn)知功能時(shí)提高神經(jīng)元興奮性的具體機(jī)制及rTMS改善認(rèn)知功能相關(guān)的物質(zhì)基礎(chǔ)目前還不是十分清楚。 海馬和額皮層是與認(rèn)知功能密切相關(guān)的腦區(qū)，在老化過(guò)程和一些神經(jīng)系統(tǒng)退行性疾病中也是最易受損傷的區(qū)域。研究表明海馬神經(jīng)元興奮性在正常老化過(guò)程中是下降的，并表現(xiàn)為后超極化幅度的增大、靜息電位的超極化。神經(jīng)元的信息傳遞編碼為動(dòng)作電位進(jìn)行傳遞，因此，如果動(dòng)作電位的形成變慢，信息傳遞速率會(huì)受到影響，這樣在神經(jīng)網(wǎng)絡(luò)信息傳遞中，效率就會(huì)降低。研究已經(jīng)證明與青年個(gè)體相比，老年個(gè)體的神經(jīng)元興奮性顯著下降低，而神經(jīng)元興奮性的下降在認(rèn)知過(guò)程中起到了關(guān)鍵作用。神經(jīng)元興奮性降低的具體機(jī)制--物質(zhì)基礎(chǔ)，是如何變化的。這一變化在病理生理刺激，基因改變等作用方式下如何表現(xiàn)為動(dòng)態(tài)的、多系統(tǒng)的變化。應(yīng)用生物體液和組織對(duì)機(jī)體病理機(jī)制進(jìn)行代謝物質(zhì)的檢測(cè)，結(jié)合非靶標(biāo)多元統(tǒng)計(jì)分析方法，分析疾病過(guò)程中的物質(zhì)變化基礎(chǔ)，目前在許多領(lǐng)域得到了廣泛應(yīng)用。這種物質(zhì)檢測(cè)分析方法的優(yōu)勢(shì)是在疾病預(yù)防和治療過(guò)程中，可以發(fā)現(xiàn)機(jī)體生化改變的生物標(biāo)志物。在對(duì)AD疾病的研究中，已有應(yīng)用非靶標(biāo)多元統(tǒng)計(jì)方法對(duì)AD病人腦脊液進(jìn)行了分析，發(fā)現(xiàn)AD病人機(jī)體的新陳代謝與正常對(duì)照人員相比，發(fā)生了明顯變化。 腦老化是腦組織隨著年齡增長(zhǎng)發(fā)生的組織結(jié)構(gòu)和功能的變化。隨著年齡的增長(zhǎng)，個(gè)體在腦老化過(guò)程中可表現(xiàn)為學(xué)習(xí)記憶能力的降低。嚙齒類動(dòng)物作為實(shí)驗(yàn)?zāi)Ｐ脱芯磕X老化及老化相關(guān)的認(rèn)知功能障礙具有很多優(yōu)點(diǎn)：嚙齒類動(dòng)物的海馬和前額皮層在老化中與人類相似，是非常容易受損的，并伴有結(jié)構(gòu)和功能的變化。昆明小鼠在老化過(guò)程中可表現(xiàn)出認(rèn)知功能的損傷，是研究腦老化的理想動(dòng)物模型。在對(duì)嚙齒類動(dòng)物進(jìn)行認(rèn)知功能評(píng)估的行為學(xué)實(shí)驗(yàn)中，被動(dòng)逃避反應(yīng)實(shí)驗(yàn)和新物體識(shí)別實(shí)驗(yàn)是經(jīng)典的認(rèn)知功能測(cè)試方法。 本課題中我們觀察了rTMS是如何改善昆明小鼠老化過(guò)程中認(rèn)知功能的損傷，及其內(nèi)在電生理機(jī)制和代謝物質(zhì)基礎(chǔ)。 1rTMS改善老化引起的認(rèn)知功能障礙 觀察rTMS是否可以改善昆明小鼠在年齡增長(zhǎng)過(guò)程中出現(xiàn)的認(rèn)知功能損害。為證明rTMS對(duì)認(rèn)知功能的影響，應(yīng)用被動(dòng)逃避反應(yīng)實(shí)驗(yàn)和新物體識(shí)別實(shí)驗(yàn)對(duì)小鼠的認(rèn)知功能進(jìn)行檢測(cè)。 方法：3-4月齡（青年）昆明小鼠，9-10月齡（成年）昆明小鼠，16-17月齡（老年）昆明小鼠。在實(shí)驗(yàn)室恒溫20-25攝氏度適應(yīng)飼養(yǎng)1天以適應(yīng)實(shí)驗(yàn)室環(huán)境，然后用于實(shí)驗(yàn)。 實(shí)驗(yàn)分組： （1）老年rTMS組：16-17月齡老年昆明小鼠，磁頭于小鼠的顱頂部每天進(jìn)行10組頻率為25赫茲的磁刺激，總共刺激脈沖數(shù)為1000個(gè)，連續(xù)14天。 （2）老年sham組：16-17月齡老年昆明小鼠，以磁頭反面于小鼠顱頂部進(jìn)行與rTMS組相似的無(wú)功能的磁刺激。 （3）成年組：9-10月齡成年昆明小鼠，與老年sham組小鼠刺激方式相同。 （4）青年組：3-4月齡青年昆明小鼠，與老年sham組小鼠刺激方式相同。 各組動(dòng)物在相同環(huán)境下飼養(yǎng)，然后通過(guò)被動(dòng)逃避反應(yīng)實(shí)驗(yàn)和新物體識(shí)別實(shí)驗(yàn)測(cè)試各組動(dòng)物學(xué)習(xí)記憶能力的差異。 結(jié)果：新物體識(shí)別實(shí)驗(yàn)成績(jī)顯示，在1h時(shí)間點(diǎn)，小鼠觸碰兩物體的總時(shí)間在青年組、成年組、老年組之間沒有明顯差異，在24h小鼠觸碰兩物體的總時(shí)間在三組之間同樣也沒有發(fā)現(xiàn)顯著差異。在1h時(shí)間點(diǎn)，青年組和成年組之間的認(rèn)知指數(shù)沒有明顯差異；與青年組和成年組相比，老年組的認(rèn)知指數(shù)顯著降低（P0.05）。同樣在24h時(shí)間點(diǎn)，與青年和成年組相比，老年組小鼠的認(rèn)知指數(shù)顯著降低（P0.05）；而青年組和成年組之間的認(rèn)知指數(shù)沒有顯著差異。在1h時(shí)間點(diǎn)，小鼠觸碰兩物體的總時(shí)間在老年組和老年rTMS組沒有明顯差異，同樣在24h也沒有發(fā)現(xiàn)顯著差異。在1h時(shí)間點(diǎn)，與老年組相比，老年rTMS組的認(rèn)知指數(shù)顯著提高（P0.05）。同樣在24h時(shí)間點(diǎn)，與老年組相比，老年rTMS組小鼠的認(rèn)知指數(shù)顯著提高（P0.05）。 被動(dòng)逃避反應(yīng)實(shí)驗(yàn)成績(jī)顯示，適應(yīng)階段的潛伏期在青年組、成年組和老年組沒有顯著差異。與青年組和成年組相比，學(xué)習(xí)階段的電擊次數(shù)在老年昆明鼠明顯增多（P0.05），而青年組和成年組之間無(wú)顯著差異。與青年鼠和成年鼠相比，記憶階段的被動(dòng)逃避潛伏期在老年鼠出現(xiàn)了顯著縮短（P0.05），同樣青年組和成年組之間沒有顯著差異。被動(dòng)逃避反應(yīng)實(shí)驗(yàn)適應(yīng)階段的潛伏期在老年組和老年rTMS組沒有顯著差異。與老年組相比，學(xué)習(xí)階段的電擊次數(shù)在老年rTMS昆明鼠明顯減少（P0.05）。同樣與老年鼠相比，記憶階段的被動(dòng)逃避潛伏期在老年rTMS鼠出現(xiàn)了顯著增長(zhǎng)（P0.05）。 以上結(jié)果提示，昆明小鼠的認(rèn)知功能在青年組和成年組沒有出現(xiàn)明顯差異，而在16月齡時(shí)開始出現(xiàn)下降，而應(yīng)用rTMS可以改善老化引起的認(rèn)知功能損傷。2rTMS改善老化相關(guān)的神經(jīng)元電生理變化 觀察rTMS是否可以通過(guò)改善電壓依賴性鈣通道（VDCC）來(lái)調(diào)節(jié)神經(jīng)元興奮性，進(jìn)而改善老年小鼠的認(rèn)知功能障礙。 方法：3-4月齡昆明小鼠，16-17月齡昆明小鼠。在相同實(shí)驗(yàn)室條件飼養(yǎng)，實(shí)驗(yàn)室恒溫20-25攝氏度，然后用于實(shí)驗(yàn)。 實(shí)驗(yàn)分組： （1）老年rTMS組：16-17月齡老年小鼠，磁頭于小鼠的顱頂部每天進(jìn)行10組頻率為25赫茲的磁刺激，總共刺激脈沖數(shù)為1000個(gè)，連續(xù)14天。 （2）老年sham組：16-17月齡老年小鼠，以磁頭反面于小鼠顱頂部進(jìn)行與rTMS組相似的無(wú)功能的磁刺激。 （3）青年組：3-4月齡青年小鼠，與老年sham組小鼠刺激方式相同。 各組動(dòng)物在相同環(huán)境下飼養(yǎng)，然后通過(guò)行為學(xué)實(shí)驗(yàn)測(cè)試后，而后進(jìn)行神經(jīng)元興奮性，VDCC等電生理指標(biāo)的記錄。 結(jié)果：全細(xì)胞電流鉗記錄結(jié)果顯示，rTMS可以改善老化引起的神經(jīng)元興奮性變化。與青年鼠相比，在老年鼠海馬CA1區(qū)的神經(jīng)元靜息電位發(fā)生了顯著超級(jí)化（P0.05）。在應(yīng)用rTMS后發(fā)現(xiàn)，與老年鼠相比，在老年磁刺激組小鼠海馬CA1區(qū)的神經(jīng)元靜息電位顯著去極化（P0.05）。與青年組相比，老年組海馬CA1區(qū)神經(jīng)元的動(dòng)作電位產(chǎn)生頻率顯著下降（P0.05）。而高頻經(jīng)顱磁刺激可以顯著提高老年神經(jīng)元的動(dòng)作電位的產(chǎn)生頻率（P0.05）。同樣與青年組相比，在老年組海馬CA1區(qū)神經(jīng)元的后超極化幅度顯著增大（P0.05）。而應(yīng)用rTMS后，可顯著降低老年組的后超級(jí)化幅度（P0.05）。而動(dòng)作電位的閾值記錄結(jié)果顯示，在青年組、老年組和老年磁刺激組之間，沒有發(fā)現(xiàn)顯著差異。 全細(xì)胞電流鉗記錄結(jié)果顯示，rTMS可以顯著降低老年海馬CA1區(qū)神經(jīng)元的VDCC。與老年對(duì)照組神經(jīng)元相比，在測(cè)試電壓分別為-20mV、-10mV和0mV時(shí)，在老年rTMS組神經(jīng)元所記錄的電流強(qiáng)度均顯著降低（P0.05）。 以上結(jié)果表明，rTMS可以通過(guò)改善VDCC來(lái)調(diào)節(jié)神經(jīng)元興奮性，進(jìn)而改善老年小鼠的認(rèn)知功能障礙。3rTMS改善老化相關(guān)的腦組織代謝產(chǎn)物變化 觀察應(yīng)用氣質(zhì)聯(lián)用分析方法對(duì)小鼠腦組織代謝產(chǎn)物進(jìn)行檢測(cè)，應(yīng)用偏最小二乘法判別分析（PLS-DA）和主成分分析（PCA）方法對(duì)結(jié)果進(jìn)行分析，進(jìn)一步應(yīng)用one-wayANOVA統(tǒng)計(jì)方法深入分析差異代謝物。 方法：3-4月齡昆明小鼠，9-10月齡昆明小鼠，16-17月齡昆明小鼠。在相同實(shí)驗(yàn)室條件飼養(yǎng)，實(shí)驗(yàn)室恒溫20-25攝氏度，然后用于實(shí)驗(yàn)。 實(shí)驗(yàn)分組： （1）老年rTMS組：16-17月齡老年小鼠，磁頭于小鼠的顱頂部每天進(jìn)行10組頻率為25赫茲的磁刺激，總共刺激脈沖數(shù)為1000個(gè)，連續(xù)14天。 （2）老年sham組：16-17月齡老年小鼠，以磁頭反面于小鼠顱頂部進(jìn)行與rTMS組相似的無(wú)功能的磁刺激。 （3）青年組：3-4月齡青年小鼠，與老年sham組小鼠刺激方式相同。 各組動(dòng)物在相同環(huán)境下飼養(yǎng)，然后通過(guò)行為學(xué)實(shí)驗(yàn)測(cè)試后，應(yīng)用氣質(zhì)聯(lián)用方法進(jìn)行腦組織代謝產(chǎn)物的測(cè)試。 結(jié)果：腦組織代謝物輪廓在老化過(guò)程中和rTMS后的變化。PLS-DA得分圖顯示，三組樣本被分布到了不同的區(qū)域。前兩個(gè)主成分的累積R2Y是0.84，Q2是0.69。根據(jù)VIP1，91種變量被選出來(lái)作為差異變量，其中一些變量被確定來(lái)自同一中代謝物，合并這些來(lái)自同一代謝產(chǎn)物的變量后，共得到23種差異代謝產(chǎn)物。 進(jìn)一步應(yīng)用one-wayANOVA對(duì)這些差異代謝物進(jìn)行進(jìn)一步統(tǒng)計(jì)，發(fā)現(xiàn)這23種代謝物在青年組、老年組和老年磁刺激組具有顯著性差異。與青年組相比，16種代謝產(chǎn)物在老年組發(fā)生了顯著變化，其中丙氨酸、磷酸、絲氨酸、蘇氨酸、蘋果酸、乳酸、尿素和肌醇的含量顯著下降，GABA、檸檬酸、油酸、5,8,11,14,17-二十碳五烯酸、單硬脂酸甘油脂、反式-9-十八碳烯酸、抗壞血酸和膽固醇含量顯著增多（P0.05）。與老年對(duì)照組小鼠相比，在老年rTMS組小鼠，21種代謝產(chǎn)物發(fā)生了變化，其中磷酸、富馬酸、蘇氨酸、蘋果酸、檸檬酸、丙氨酸、尿素、GABA、絲氨酸、焦磷酸、乳酸、焦谷氨酸、天冬氨酸、肌酐、天冬氨酸和膽固醇含量顯著減少（P0.05），油酸、5,8,11,14,17-二十碳五烯酸、N乙酰天冬氨酸、甘油磷酸含量顯著增多（P0.05）。 根據(jù)所篩選出的23種代謝差異物對(duì)青年組、老年組和老年rTMS組進(jìn)行驗(yàn)證性主成分分析。得分圖顯示，根據(jù)前兩個(gè)主成分，青年組、老年組和老年磁刺激組被顯著區(qū)分開來(lái)，R2X和Q2分別是0.60和0.45。 對(duì)所有差異代謝產(chǎn)物進(jìn)行變化趨勢(shì)分析，，膽固醇、GABA、抗壞血酸和檸檬酸為所篩選出的rTMS逆轉(zhuǎn)腦組織老化過(guò)程中的代謝產(chǎn)物。對(duì)被動(dòng)逃避反應(yīng)實(shí)驗(yàn)的成績(jī)和膽固醇、GABA、抗壞血酸和檸檬酸的水平進(jìn)行相關(guān)性分析。發(fā)現(xiàn)，膽固醇和被動(dòng)逃避潛伏期的Pearson Correlation是-0.413（P0.05），GABA、抗壞血酸和檸檬酸和被動(dòng)逃避潛伏期的PearsonCorrelation是-0.25、-0.080和-0.273。 上述結(jié)果表明，rTMS可以改善老化過(guò)程中認(rèn)知功能相關(guān)的代謝產(chǎn)物紊亂，在這些差異代謝產(chǎn)物中，膽固醇可能是一個(gè)較為特殊、重要的認(rèn)知功能相關(guān)的代謝標(biāo)志物。 結(jié)論 （1）昆明小鼠的認(rèn)知功能在青年組和成年組沒有出現(xiàn)明顯差異，而在16月齡時(shí)開始出現(xiàn)下降，應(yīng)用rTMS可以改善老化引起的認(rèn)知功能損傷。 （2）rTMS可以通過(guò)改善VDCC來(lái)調(diào)節(jié)神經(jīng)元興奮性，進(jìn)而改善老年小鼠的認(rèn)知功能障礙。 （3）rTMS可影響腦內(nèi)代謝產(chǎn)物的變化，改善老化過(guò)程中認(rèn)知功能相關(guān)的代謝產(chǎn)物紊亂，在這些差異代謝產(chǎn)物中，膽固醇可能是一個(gè)較為特殊、重要的認(rèn)知功能相關(guān)的代謝標(biāo)志物。
[Abstract]:Repeated transcranial magnetic stimulation (rTMS) is a non-invasive and non-invasive physical therapy that has attracted increasing attention. It has been reported that rTMS can improve cognitive impairment in normal aging and Alzheimer's disease (AD) patients. The effects of rTMS on neuronal excitability and synaptic plasticity were reported. The effects of rTMS on synaptic plasticity were manifested as long-term potentiation (LTP). Animal experiments showed that LTP in hippocampal slices was significantly enhanced while rTMS was used to improve cognitive function. Studies on gene, protein and metabolite levels have shown that rTMS can protect neurons by regulating the expression of plasticity-related genes, protein and metabolite homeostasis. However, the specific mechanism of high-frequency rTMS in improving cognitive function and the substances related to rTMS in improving cognitive function are discussed. The foundation is not clear at the moment.
The hippocampus and frontal cortex are brain regions closely related to cognitive function, and are also the most vulnerable areas in the aging process and some neurodegenerative diseases. Studies have shown that the excitability of hippocampal neurons decreases during normal aging, and shows an increase in the amplitude of post-hyperpolarization and the hyperpolarization of resting potential. Transmission codes are action potentials, so if action potentials are slowed down, the rate of information transmission is affected, and thus the efficiency of neural network information transmission is reduced. It plays a key role in the process. The specific mechanism of neuronal excitability reduction, the material basis, is how to change. How this change in pathophysiological stimuli, gene changes and other ways of action to show dynamic, multi-system changes. Biological fluids and tissues on the body's pathological mechanisms for the detection of metabolic substances, combined with non- Target multivariate statistical analysis is widely used in many fields to analyze the basis of material changes in the course of disease. The advantage of this method is that biochemical markers can be found in the process of disease prevention and treatment. Methods The cerebrospinal fluid of AD patients was analyzed. It was found that the metabolism of AD patients was significantly different from that of normal controls.
Brain aging is a change in the structure and function of brain tissues with age.As individuals age, their learning and memory abilities decrease during brain aging.Rodents as experimental models have many advantages in studying cognitive impairment related to brain aging and aging: the hippocampus of rodents. The prefrontal cortex is very vulnerable to damage and accompanied by structural and functional changes in aging. Kunming mice exhibit cognitive impairment during aging and are ideal animal models for studying brain aging. And the new object recognition experiment is a classic cognitive function test method.
In this study, we observed how rTMS improves cognitive impairment in aging Kunming mice, and its intrinsic electrophysiological mechanism and metabolic basis.
1rTMS improves cognitive impairment caused by aging
To investigate whether rTMS can ameliorate cognitive impairment in Kunming mice during aging, passive avoidance response (PAR) test and new object recognition (NER) test were used to test the cognitive impairment in mice.
Methods: Kunming mice aged from 3 to 4 months, Kunming mice aged from 9 to 10 months and Kunming mice aged from 16 to 17 months were raised at 20 to 25 degrees Celsius in the laboratory for one day to adapt to the laboratory environment.
Experimental grouping:
(1) Aged rTMS group: aged Kunming mice aged 16-17 months were treated with 25 Hz magnetic stimulation at 10 groups per day on the top of the skull. The total number of stimulation pulses was 1000, lasting 14 days.
(2) Aged sham group: aged Kunming mice aged 16-17 months were treated with magnetic head reversed on the cranial top of the mice with similar nonfunctional magnetic stimulation as rTMS group.
(3) adult group: 9-10 month old adult Kunming mice were the same as the old sham group mice.
(4) young group: 3-4 month old young Kunming mice were the same as the old sham group mice.
Each group was fed in the same environment, and then the learning and memory abilities of each group were tested by passive escape response test and new object recognition test.
Results: The results of the new object recognition experiment showed that there was no significant difference in the total time of touching two objects between the young group, the adult group and the old group at 1 hour, and there was no significant difference in the total time of touching two objects between the three groups at 24 hours. The cognitive index of the aged group was significantly lower than that of the young group and the adult group (P 0.05). At the same time, the cognitive index of the aged group was significantly lower than that of the young group and the adult group (P 0.05). There was no significant difference in the cognitive index between the young group and the adult group. There was no significant difference in time between the elderly group and the elderly rTMS group, and no significant difference was found at 24 hours. At 1 hour, the cognitive index of the elderly rTMS group was significantly higher than that of the elderly group (P 0.05). At the same time, the cognitive index of the aged rTMS group was significantly higher than that of the elderly group (P 0.05).
The results of passive evasion test showed that there was no significant difference in the latency of adaptation stage between the young group, the adult group and the old group. There was no significant difference in the latency of passive escape reaction between the aged group and the adult group (P 0.05). There was no significant difference in the latency of passive escape reaction between the aged group and the aged rTMS group. The passive escape latency of the memory stage in the aged rTMS mice increased significantly (P 0.05).
These results suggest that there is no significant difference in cognitive function between young and adult Kunming mice, but it begins to decline at the age of 16 months. rTMS can improve cognitive impairment induced by aging. 2rTMS can improve neuronal electrophysiological changes associated with aging.
To observe whether rTMS can regulate neuronal excitability by improving voltage-dependent calcium channel (VDCC) and improve cognitive dysfunction in aged mice.
METHODS: Kunming mice aged 3-4 months and Kunming mice aged 16-17 months were fed in the same laboratory conditions at a constant temperature of 20-25 degrees Celsius in the laboratory, and then used in the experiment.
Experimental grouping:
(1) Aged rTMS group: aged 16-17 months old mice, magnetic head in the top of the mouse cranium every day for 10 groups of 25 Hz magnetic stimulation, a total of 1000 stimulation pulses, 14 days.
(2) Aged sham group: aged 16-17 months old mice were treated with magnetic head on the head of the head of the mice, which was similar to that of rTMS group.
(3) young group: 3-4 month old young mice were the same as the old sham group mice.
The animals in each group were fed in the same environment, then were tested by behavioral experiments, and then the neuronal excitability, VDCC and other electrophysiological indicators were recorded.
Results: Whole cell current clamp recording showed that rTMS could ameliorate neuronal excitability induced by aging. Compared with young rats, resting potentials of neurons in hippocampal CA1 region of aged rats were significantly increased (P 0.05). The frequency of action potential production in hippocampal CA1 neurons in the aged group was significantly lower than that in the young group (P 0.05). High frequency transcranial magnetic stimulation could significantly increase the frequency of action potential production in the aged neurons (P 0.05). The amplitude of posthyperpolarization in hippocampal CA1 neurons in the aged group was also higher than that in the young group. After rTMS was used, the post-hyper amplitude (P 0.05) of the aged group was significantly decreased, while the threshold of action potential was recorded. There was no significant difference between the young group, the aged group and the aged magnetic stimulation group.
Whole-cell current clamp recording showed that rTMS could significantly reduce the VDCC of neurons in hippocampal CA1 region in the aged. Compared with the aged control group, the recorded current intensity of neurons in the aged rTMS group decreased significantly at - 20 mV, - 10 mV and 0 mV respectively (P 0.05).
These results suggest that rTMS can regulate neuronal excitability by improving VDCC, thereby improving cognitive impairment in aged mice. 3rTMS can improve metabolites of aging-related brain tissues.
The metabolites in brain tissue of mice were detected by GC-MS, the results were analyzed by PLS-DA and PCA, and one-way ANOVA was used to analyze the metabolites.
Methods: Kunming mice aged from 3 to 4 months, Kunming mice aged from 9 to 10 months and Kunming mice aged from 16 to 17 months were fed under the same laboratory conditions at a constant temperature of 20 to 25 degrees Celsius in the laboratory.
Experimental grouping:
(1) Aged rTMS group: aged 16-17 months old mice, magnetic head in the top of the mouse cranium every day for 10 groups of 25 Hz magnetic stimulation, a total of 1000 stimulation pulses, 14 days.
(2) Aged sham group: aged 16-17 months old mice were treated with magnetic head on the head of the head of the mice, which was similar to that of rTMS group.
(3) young group: 3-4 month old young mice were the same as the old sham group mice.
All groups of animals were fed in the same environment, and then the metabolites of brain tissue were measured by GC-MS after behavioral tests.
Results: Changes in metabolite profiles of brain tissues during aging and after rTMS. PLS-DA scores showed that three groups of samples were distributed in different regions. The cumulative R2Y of the first two principal components was 0.84 and Q2 was 0.69. A total of 23 differential metabolites were obtained from the variables of the same metabolite.
Furthermore, one-way ANOVA was used to analyze these metabolites. The results showed that the 23 metabolites were significantly different in the youth group, the elderly group and the elderly magnetic stimulation group. Compared with the youth group, 16 metabolites had significant changes in the elderly group, including alanine, phosphoric acid, serine, threonine, malic acid, lactic acid, urea. The contents of GABA, citric acid, oleic acid, 5,8,11,14,17-eicosapentaenoic acid, glycerin monostearate, trans-9-octadecanoic acid, ascorbic acid and cholesterol increased significantly (P 0.05). Compared with the aged control group, 21 metabolites in the aged rTMS group were changed, including phosphoric acid, fumaric acid, threonine. Contents of acid, malic acid, citric acid, alanine, urea, GABA, serine, pyrophosphate, lactic acid, pyroglutamic acid, aspartic acid, creatinine, aspartate and cholesterol decreased significantly (P 0.05), oleic acid, 5, 8, 11, 14, 17-eicosapentaene.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R741.044

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