Non-motor Behavioral Alterations of PGC-1α-Deficient Mice - A Peculiar Phenotype With Slight Male Preponderance and No Apparent Progression.
Non-motor Behavioral Alterations of PGC-1α-Deficient Mice - A Peculiar Phenotype With Slight Male Preponderance and No Apparent Progression.
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DOI：
10.3389/fnbeh.2018.00180
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发表时间：
2018
影响因子：
3
通讯作者：
Klivenyi P
中科院分区：
文献类型：
--
作者：
Szalardy L;Molnar MF;Zadori D;Cseh EK;Veres G;Kovacs GG;Vecsei L;Klivenyi P
过氧化物酶体增殖物激活受体γ共激活因子-1 α（PGC-1α）的功能障碍与各种神经退行性疾病和神经精神疾病有关;然而，关于PGC-1α缺陷动物精神行为改变的报道很少。本研究回顾了先前对不同PGC-1α缺陷小鼠品系进行的焦虑相关、抑郁相关和海马记忆相关观察，这些观察是在对全身全长（FL-）PGC-1α缺陷小鼠进行的大规模分析中进行的。对从两种性别中招募的涵盖广泛年龄范围的动物进行检查，包括开放视野、高架十字迷宫、明暗箱、悬尾试验和空间识别双试验Y迷宫等范例。研究结果显示，没有迹象表明先前报告的焦虑样行为，但揭示了一个意想不到的表型与减少焦虑行为一致，在整个不同的范例，轻微的男性优势。这与绝望样快感缺失行为有关，与先前报道的一致，但与先前提出的犬尿烯酸合成的外周或大脑改变无关。虽然雄性FL-PGC-1α缺陷小鼠在基于校园的空间学习范式中表现较差，但基因型总体上与空间记忆障碍无关，这与先前的观察结果相矛盾。没有观察到的变化随着年龄的增长而恶化，类似于以前报道的运动改变。最有可能的贡献者，这种奇特的表型进行了讨论，与临床病理相关性绘制。作为第一个在同一PGC-1α缺陷株中解决这些行为领域的研究，我们的研究结果扩展了关于PGC-1α功能障碍的复杂体内效应的知识，并为PGC-1α与神经精神疾病相关的研究领域增加了重要的注释。
Dysfunction of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) has been linked to various neurodegenerative and neuropsychiatric disorders; however, reports on psychic behavioral alterations on PGC-1α-deficient animals are sparse. The present study revisited prior observations of anxiety-related, depression-related, and hippocampal memory-related observations having been made on different PGC-1α-deficient murine strains, in a large-scale analysis on whole-body full-length (FL-)PGC-1α-deficient mice. The examinations were performed on animals covering a wide age range enrolled from both sexes, and included paradigms such as the open-field, elevated plus maze, light-dark box, tail suspension test, and spatial recognition two-trial Y-maze. The findings revealed no signs of previously reported anxiety-like behavior, but revealed an unexpected phenotype with decreased anxiety behavior consistent throughout different paradigms, with slight male preponderance. This was associated with despair-like anhedonic behavior, consistent with that reported previously, but did not associate with either peripheral or brain alterations in kynurenic acid synthesis, which was previously proposed. Though male FL-PGC-1α-deficient mice tended to perform poorer in the hippocampus-based spatial learning paradigm, the genotype overall was not associated with impairment in spatial memory, contradicting with prior observations. None of the observed alterations deteriorated with age, similarly to motor alterations as reported previously. The most likely contributors of this peculiar phenotype are discussed, with clinicopathological correlations drawn. Being the first to address these behavioral domains within the same PGC-1α-deficient strain, our findings extend the knowledge about the complex in vivo effect of PGC-1α dysfunction and add important notes to research in the field of PGC-1α in connection with neuropsychiatric disorders.
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影响因子：
5.3
作者：
Knutti, D;Kaul, A;Kralli, A
通讯作者：
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影响因子：
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DOI：
10.1016/j.bbrc.2006.11.074
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影响因子：
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