皮质和纹状体脑电图和阿扑吗啡在肌萎缩侧索硬化 FUS 小鼠模型中的作用。

Cortical and Striatal Electroencephalograms and Apomorphine Effects in the FUS Mouse Model of Amyotrophic Lateral Sclerosis.

机构信息

Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation.

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation.

出版信息

J Alzheimers Dis. 2021;81(4):1429-1443. doi: 10.3233/JAD-201472.

DOI:10.3233/JAD-201472

PMID:33935079

Abstract

BACKGROUND

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons resulting in muscle atrophy. In contrast to the lower motor neurons, the role of upper (cortical) neurons in ALS is yet unclear. Maturation of locomotor networks is supported by dopaminergic (DA) projections from substantia nigra to the spinal cord and striatum.

OBJECTIVE

To examine the contribution of DA mediation in the striatum-cortex networks in ALS progression.

METHODS

We studied electroencephalogram (EEG) from striatal putamen (Pt) and primary motor cortex (M1) in ΔFUS(1-359)-transgenic (Tg) mice, a model of ALS. EEG from M1 and Pt were recorded in freely moving young (2-month-old) and older (5-month-old) Tg and non-transgenic (nTg) mice. EEG spectra were analyzed for 30 min before and for 60 min after systemic injection of a DA mimetic, apomorphine (APO), and saline.

RESULTS

In young Tg versus nTg mice, baseline EEG spectra in M1 were comparable, whereas in Pt, beta activity in Tg mice was enhanced. In older Tg versus nTg mice, beta dominated in EEG from both M1 and Pt, whereas theta and delta 2 activities were reduced. In younger Tg versus nTg mice, APO increased theta and decreased beta 2 predominantly in M1. In older mice, APO effects in these frequency bands were inversed and accompanied by enhanced delta 2 and attenuated alpha in Tg versus nTg mice.

CONCLUSION

We suggest that revealed EEG modifications in ΔFUS(1-359)-transgenic mice are associated with early alterations in the striatum-cortex interrelations and DA transmission followed by adaptive intracerebral transformations.

摘要

背景

肌萎缩侧索硬化症（ALS）的特征是运动神经元退化导致肌肉萎缩。与下运动神经元不同，皮质（皮质）神经元在 ALS 中的作用尚不清楚。纹状体-脊髓和纹状体的黑质多巴胺（DA）投射支持运动网络的成熟。

目的

检查 DA 介导在 ALS 进展中的纹状体-皮质网络中的作用。

方法

我们研究了纹状体苍白球（Pt）和原发性运动皮层（M1）的脑电图（EEG）在ΔFUS（1-359）-转染（Tg）小鼠中，这是 ALS 的模型。在自由移动的年轻（2 个月大）和老年（5 个月大）Tg 和非转染（nTg）小鼠中记录了来自 M1 和 Pt 的 EEG。在系统注射多巴胺类似物阿朴吗啡（APO）和生理盐水前后 30 分钟分析 EEG 频谱。

结果

与 nTg 小鼠相比，年轻的 Tg 小鼠的 M1 中的基线 EEG 频谱相当，而在 Pt 中，Tg 小鼠的β活性增强。与 nTg 小鼠相比，老年 Tg 小鼠的 EEG 中β占主导地位，而θ和δ 2 活动减少。在年轻的 Tg 与 nTg 小鼠中，APO 主要增加了 M1 中的θ并减少了β 2。在老年小鼠中，这些频带中的 APO 作用相反，并伴有 Tg 与 nTg 小鼠中增强的δ 2 和减弱的α。