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社会环境可改善酪氨酸羟化酶单倍不足雌性小鼠的行为和免疫损伤。

Social Environment Ameliorates Behavioral and Immune Impairments in Tyrosine Hydroxylase Haploinsufficient Female Mice.

机构信息

Department of Genetics, Physiology and Microbiology (Physiology Unit), School of Biology, Complutense University of Madrid, José Antonio Nováis 12, 28040, Madrid, Spain.

Institute of Investigation of Hospital 12 de Octubre (i+12), 28041, Madrid, Spain.

出版信息

J Neuroimmune Pharmacol. 2021 Sep;16(3):548-566. doi: 10.1007/s11481-020-09947-2. Epub 2020 Aug 9.

Abstract

The social environment can influence the functional capacity of nervous and immune systems, and consequently the state of health, especially in aged individuals. Adult female tyrosine hydroxylase haploinsufficient (TH-HZ) mice exhibit behavioral impairments, premature immunosenescence and oxidative- inflammatory stress. All these deteriorations are associated with a lower lifespan than wild type (WT) counterparts. The aim was to analyze whether the cohabitation with WT animals could revert or at least ameliorate the deterioration in the nervous and immune systems that female TH-HZ mice show at adult age. Female TH-HZ and WT mice at age of 3-4 weeks were divided into following groups: control TH-HZ (5 TH-HZ mice in the cage; TH-HZ100%), control WT (5 WT mice in the cage; WT100%), TH-HZ > 50% and WT < 50% (5 TH-HZ with 2 WT mice in each cage) as well as TH-HZ < 50% and WT > 50% (2 TH-HZ and 5 WT mice in each cage). At the age of 37-38 weeks, all mice were submitted to a battery of behavioral tests, evaluating sensorimotor abilities, exploratory capacities and anxiety-like behaviors. Subsequently, peritoneal leukocytes were extracted and several immune functions as well as oxidative and inflammatory stress parameters were analyzed. The results showed that the TH-HZ < 50% group had improved behavioral responses, especially anxiety-like behaviors, and the immunosenescence and oxidative stress of their peritoneal leukocytes were ameliorated. However, WT mice that cohabited with TH-HZ mice presented higher anxiety-like behaviors and deterioration in immune functions and in their inflammatory stress parameters. Thus, this social environment is capable of ameliorating the impairments associated with a haploinsufficiency of the th gene. Graphical Abstract.

摘要

社会环境可以影响神经和免疫系统的功能能力,从而影响健康状况,尤其是在老年人中。成年雌性酪氨酸羟化酶单倍不足(TH-HZ)小鼠表现出行为障碍、免疫衰老和氧化-炎症应激过早发生。所有这些恶化都与比野生型(WT)对照寿命更短有关。目的是分析与 WT 动物共同生活是否可以逆转或至少改善成年 TH-HZ 雌性小鼠表现出的神经系统和免疫系统的恶化。3-4 周龄的雌性 TH-HZ 和 WT 小鼠分为以下几组:对照组 TH-HZ(笼子里有 5 只 TH-HZ 小鼠;TH-HZ100%)、对照组 WT(笼子里有 5 只 WT 小鼠;WT100%)、TH-HZ > 50% 和 WT < 50%(每笼 5 只 TH-HZ 和 2 只 WT 小鼠)以及 TH-HZ < 50% 和 WT > 50%(每笼 2 只 TH-HZ 和 5 只 WT 小鼠)。在 37-38 周龄时,所有小鼠都接受了一系列行为测试,评估感觉运动能力、探索能力和焦虑样行为。随后,提取腹膜白细胞并分析几种免疫功能以及氧化和炎症应激参数。结果表明,TH-HZ < 50%组的行为反应得到改善,尤其是焦虑样行为,其腹膜白细胞的免疫衰老和氧化应激得到改善。然而,与 TH-HZ 小鼠共同生活的 WT 小鼠表现出更高的焦虑样行为以及免疫功能和炎症应激参数的恶化。因此,这种社会环境能够改善与 th 基因单倍不足相关的损伤。

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