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缺乏耳石的mlh突变小鼠的行为和神经化学特征

Behavioral and neurochemical characterization of the mlh mutant mice lacking otoconia.

作者信息

Manes Marianna, Garcia-Gomes Mariana de Souza Aranha, Sandini Thaísa Meira, Zaccarelli-Magalhães Julia, Florio Jorge Camilo, Alexandre-Ribeiro Sandra Regina, Wadt Danilo, Bernardi Maria Martha, Massironi Silvia Maria Gomes, Mori Claudia Madalena Cabrera

机构信息

Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo (USP), Brazil.

School of Pharmaceutical Sciences, University of São Paulo (USP), Brazil.

出版信息

Behav Brain Res. 2019 Feb 1;359:958-966. doi: 10.1016/j.bbr.2018.06.012. Epub 2018 Jun 18.

Abstract

Otoconia are crucial for the correct processing of positional information and orientation. Mice lacking otoconia cannot sense the direction of the gravity vector and cannot swim properly. This study aims to characterize the behavior of mergulhador (mlh), otoconia-deficient mutant mice. Additionally, the central catecholamine levels were evaluated to investigate possible correlations between behaviors and central neurotransmitters. A sequence of behavioral tests was used to evaluate the parameters related to the general activity, sensory nervous system, psychomotor system, and autonomous nervous system, in addition to measuring the acquisition of spatial and declarative memory, anxiety-like behavior, motor coordination, and swimming behavior of the mlh mutant mice. As well, the neurotransmitter levels in the cerebellum, striatum, frontal cortex, and hippocampus were measured. Relative to BALB/c mice, the mutant mlh mice showed 1) reduced locomotor and rearing behavior, increased auricular and touch reflexes, decreased motor coordination and increased micturition; 2) decreased responses in the T-maze and aversive wooden beam tests; 3) increased time of immobility in the tail suspension test; 4) no effects in the elevated plus maze or object recognition test; 5) an inability to swim; and 6) reduced turnover of dopaminergic system in the cerebellum, striatum, and frontal cortex. Thus, in our mlh mutant mice, otoconia deficiency reduced the motor, sensory and spatial learning behaviors likely by impairing balance. We did not rule out the role of the dopaminergic system in all behavioral deficits of the mlh mutant mice.

摘要

耳石对于正确处理位置信息和定向至关重要。缺乏耳石的小鼠无法感知重力矢量的方向,也无法正常游泳。本研究旨在描述mergulhador(mlh)耳石缺陷突变小鼠的行为特征。此外,评估了中枢儿茶酚胺水平,以研究行为与中枢神经递质之间可能的相关性。除了测量mlh突变小鼠的空间和陈述性记忆获取、焦虑样行为、运动协调性和游泳行为外,还使用了一系列行为测试来评估与一般活动、感觉神经系统、精神运动系统和自主神经系统相关的参数。同时,还测量了小脑、纹状体、额叶皮质和海马体中的神经递质水平。相对于BALB/c小鼠,突变的mlh小鼠表现出:1)运动和竖毛行为减少,耳廓和触觉反射增强,运动协调性降低,排尿增加;2)在T迷宫和厌恶性木梁测试中的反应减少;3)在尾悬测试中不动时间增加;4)在高架十字迷宫或物体识别测试中无影响;5)无法游泳;6)小脑、纹状体和额叶皮质中多巴胺能系统的周转率降低。因此,在我们的mlh突变小鼠中,耳石缺乏可能通过损害平衡而降低了运动、感觉和空间学习行为。我们并未排除多巴胺能系统在mlh突变小鼠所有行为缺陷中的作用。

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