本文關(guān)鍵詞：γ-氨基丁酸能神經(jīng)元條件性敲除PGC-1α基因?qū)π∈蠼箲]抑郁樣行為的影響　出處：《江蘇大學》2017年碩士論文　論文類型：學位論文

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【摘要】：【目的】構(gòu)建條件性敲除γ-氨基丁酸能神經(jīng)元中過氧化物酶體增殖物激活受體γ輔激活因子-1α(peroxisom proliferator-activated receptor-γcoactivator-1 alpha,PGC-1α)基因的小鼠,并探索條件性敲除γ-氨基丁酸能神經(jīng)元中過氧化物酶體增殖物激活受體γ輔激活因子-1α對小鼠焦慮抑郁樣行為的影響�！痉椒ā繌拿绹鳭ackson Lab引進SPF級PGC-1αflox/+雜合子小鼠,通過飼養(yǎng)、繁育獲得PGC-1αflox/flox純合子小鼠。將其與特異性在γ-氨基丁酸能神經(jīng)元表達Cre重組酶的Dlx5/6-Cre-IRES-EGFP小鼠合籠,產(chǎn)生的子代進行基因型鑒定,即可獲得特異性在γ-氨基丁酸能神經(jīng)元中敲除PGC-1α的純合子小鼠,雜合子小鼠和野生型小鼠。純合子9只,雜合子16只,野生型10只。分別做高架十字實驗,垂直型開場實驗,懸尾實驗,強迫游泳實驗。用Etho Vision軟件采集小鼠行為數(shù)據(jù),用Stat View軟件進行統(tǒng)計分析�！窘Y(jié)果】(1)成功構(gòu)建敲除PGC-1α的純合子小鼠(同時表達Loxp/loxp Cre),敲除PGC-1α的雜合子小鼠(同時表達Loxp/-Cre)及野生型小鼠(只表達Loxp或者Cre)。(2)青年期(4周)行為學實驗結(jié)果:在垂直型開場實驗中,純合子小鼠運動總距離與運動速度比雜合子(P0.05)及野生型(P0.01)顯著增加,差異有統(tǒng)計學意義;而雜合子與野生型之間無統(tǒng)計學意義。在高架十字迷宮中純合子小鼠進入開放臂頻率百分比和運動總距離比雜合子(P0.05)與野生型(P0.05)都要高,差異有統(tǒng)計學意義;雜合子和野生型之間無統(tǒng)計學意義。懸尾實驗中野生型掙扎時間比純合子(P0.05)和雜合子(P0.05)小鼠要短,差異有統(tǒng)計學意義。而純合子和雜合子小鼠之間無統(tǒng)計學意義;野生型靜止時間比純合子和雜合子長(P0.05),差異有統(tǒng)計學意義。純合子和雜合子之間無統(tǒng)計學意義。強迫游泳實驗中我們得到了與懸尾實驗相同的結(jié)果。成年期(8周)行為學實驗結(jié)果:在垂直型開場實驗中,純合子小鼠運動總距離比野生型(P0.01)顯著增加,差異有統(tǒng)計學意義;純合子與雜合子小鼠之間差異無統(tǒng)計學意義;雜合子與野生型之間無統(tǒng)計學意義。高架十字迷實驗中純合子小鼠進入開放臂頻率百分比和運動總距離比雜合子(P0.05)與野生型(P0.05)都要高,差異有統(tǒng)計學意義;雜合子和野生型之間差異無統(tǒng)計學意義。懸尾實驗中野生型掙扎時間比純合子(P0.05)和雜合子(P0.05)小鼠要短,差異有統(tǒng)計學意義。而純合子和雜合子小鼠之間無統(tǒng)計學意義;野生型靜止時間比純合子和雜合子長(P0.05),差異有統(tǒng)計學意義;純合子和雜合子之間無統(tǒng)計學意義。強迫游泳實驗中我們得到了與懸尾實驗相同的結(jié)果。4周與8周實驗對比結(jié)果:垂直型開場實驗3組小鼠運動總距離和運動速度對比都無統(tǒng)計學意義。高架十字迷宮實驗野生型和雜合子小鼠4周進入開放臂頻率百分比比8周減少,差異有統(tǒng)計學意義(P0.01);純合子小鼠對比無統(tǒng)計學意義。野生型和雜合子小鼠4周運動總距離比8周長有顯著統(tǒng)計學意義(P0.01),純合子小鼠4周運動總距離比8周長有顯著統(tǒng)計學意義(P0.05)。懸尾實驗和強迫游泳實驗結(jié)果一樣,野生型小鼠4周掙扎時間比8周短,差異有統(tǒng)計學意義(P0.01);野生型小鼠4周靜止時間比8周長,差異有統(tǒng)計學意義(P0.01)。而雜合子和純合子小鼠之間差異無統(tǒng)計學意義�！窘Y(jié)論】以上結(jié)果說明,條件性敲除γ-氨基丁酸能神經(jīng)元中PGC-1α基因后小鼠表現(xiàn)出抗焦慮抑郁樣行為。野生型小鼠的抗焦慮抑郁能力隨年齡增長而變強,但是雜合子與純合子抗焦慮抑郁樣行為無改變。
[Abstract]:[Objective] to construct conditional knockout of GABAergic neurons in peroxisome proliferator activated receptor gamma coactivator -1 alpha (peroxisom proliferator-activated receptor- coactivator-1 alpha PGC-1 gamma, alpha) gene knockout mice, and explore the GABAergic neurons of peroxisome proliferator activated receptor gamma coactivator -1 alpha effect the anxiety and depression like behaviors in mice. [Methods] SPF PGC-1 alpha flox/+ heterozygote mice were introduced from Jackson Lab in the United States, and PGC-1 alpha flox/flox homozygote mice were obtained by feeding and breeding. The specificity of GABAergic Cre recombinase expression neurons of the Dlx5/6-Cre-IRES-EGFP mice in cages, produce offspring for genotype identification, can be obtained in specific GABAergic neurons in the knockout mice homozygous except PGC-1 alpha, heterozygous mice and wild type mice. 9 homozygotes, 16 heterozygotes and 10 wild type. The cross test of viaduct, vertical opening experiment, tail suspension experiment, and forced swimming test were done respectively. The behavior data of mice were collected by Etho Vision software, and the statistical analysis was carried out by Stat View software. [results] (1) we successfully constructed homozygous mice with knockout PGC-1 alpha (simultaneously expressing Loxp/loxp Cre), knockout PGC-1 alpha heterozygous mice (simultaneously expressing Loxp/-Cre) and wild type mice (expressing Loxp or Cre only). (2) the behavioral experiment results in the youth stage (4 weeks): in the vertical opening experiment, the total distance and speed of homozygous mice were significantly higher than those of heterozygote (P0.05) and wild type (P0.01), but the difference was statistically significant, but there was no significant difference between heterozygote and wild type. In the elevated cross maze, the percentage and total distance of homozygous mice entering the open arms were higher than those of heterozygote (P0.05) and wild type (P0.05), the difference was statistically significant, and there was no significant difference between heterozygote and wild type. The struggle time of the wild type in the tail suspension experiment was shorter than that of the homozygote (P0.05) and the heterozygote (P0.05) mice, and the difference was statistically significant. There was no statistically significant difference between homozygote and heterozygote mice, and there was a significant difference between the homozygote and heterozygote length (P0.05) of the wild type. There was no statistical significance between the homozygote and the heterozygote. In the forced swimming experiment, we got the same result as the tail suspension experiment. Adult (8 weeks) the results of behavioral experiments: in the vertical opening experiment, mice homozygous for the motor total distance than the wild type (P0.01) increased significantly, the difference was statistically significant; there was no significant difference between homozygous and heterozygous mice; no statistical significance between heterozygotes and wild type. The percentage and total distance of homozygous mice entering the open arms were higher than those of heterozygote (P0.05) and wild type (P0.05). The struggle time of the wild type in the tail suspension experiment was shorter than that of the homozygote (P0.05) and the heterozygote (P0.05) mice, and the difference was statistically significant. There was no statistical significance between homozygote and heterozygous mice. The resting time of wild type was longer than that of homozygote and heterozygote (P0.05), and the difference was statistically significant. Homozygote and heterozygote were not statistically significant. In the forced swimming experiment, we got the same result as the tail suspension experiment. The results of comparison between 4 weeks and 8 weeks were compared: there was no significant difference between the total distance and the speed of movement of the 3 groups of mice in the vertical open field experiment. In the elevated maze test, the percentage of open arms in wild type and heterozygous mice decreased 4 weeks to 8 weeks, and the difference was statistically significant (P0.01). Homozygous mice had no significant difference. The total exercise distance of wild type and heterozygous mice in 4 weeks was significantly higher than that of 8 Zhou Changyou (P0.01), and the total exercise distance of homozygous mice in 4 weeks was significantly higher than that of 8 Zhou Changyou (P0.05). The results of tail suspension test and forced swimming test were the same. Wild type mice had shorter 4 weeks' struggle time than 8 weeks, and the difference was statistically significant (P0.01). The resting time of 4 weeks in wild type mice was 8 weeks, and the difference was statistically significant (P0.01). There was no significant difference between the heterozygote and the homozygote mice. [Conclusion] the above results suggest that the conditioned knockout of the PGC-1 - alpha gene in the neurons of gamma aminobutyric acid shows anti - anxiety and depressive behavior. The anti anxiety and depression ability of wild type mice increased with age, but the antidepressant behavior of heterozygotes and homozygotes did not change.
【學位授予單位】：江蘇大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R749.4

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