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帕金森病-/-大鼠模型中[F]氟脱氧葡萄糖摄取及相关行为的正电子发射断层扫描神经成像

Positron emission tomography neuroimaging of [F]fluorodeoxyglucose uptake and related behavior in the -/- rat model of Parkinson disease.

作者信息

Converse Alexander K, Krasko Maryann N, Rudisch Denis Michael, Lunaris Charlie Lenell, Nisbet Alex F, Slesarev Maxim S, Szot John C, Hoerst Andrew G, Leverson Glen E, Gallagher Catherine L, Ciucci Michelle R

机构信息

Waisman Center, University of Wisconsin-Madison, Madison, WI, United States.

Division of Otolaryngology, Department of Surgery, University of Wisconsin-Madison, Madison, WI, United States.

出版信息

Front Neurosci. 2024 Oct 15;18:1451118. doi: 10.3389/fnins.2024.1451118. eCollection 2024.

DOI:10.3389/fnins.2024.1451118
PMID:39474461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11520326/
Abstract

INTRODUCTION

Parkinson disease (PD) is a neurodegenerative condition affecting multiple sensorimotor and cognitive systems. The rat model exhibits vocal, cognitive, and limb use deficits seen in idiopathic PD. We sought to measure glucose metabolism in brain regions in and wild type (WT) rats, and to associate these to measures of ultrasonic vocalization, cognition, and limb use behavior.

METHODS

(n = 12) and WT (n = 14) rats were imaged by [F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a repeated measures design at approximately 10 months of age and 6 weeks later. Relative regional glucose metabolism was indexed by whole brain normalized FDG uptake, which was calculated for 18 regions identified for comparison. Behavioral measures included tests of communication via ultrasonic vocalization, cognition with 5-Choice Serial Reaction Time Test (5-CSRTT), and limb use with Cylinder Test and Challenge Beam.

RESULTS

Relative glucose metabolism was significantly different in rats in prelimbic area, striatum, nucleus ambiguus, globus pallidus, and posterior parietal association cortex compared to WT controls. For behavioral measures, -/- rats demonstrated quieter vocalizations with a restricted frequency range, and they showed increased number of foot-faults and hindlimb steps (shuffling) in limb motor tests. Significant behavior vs. brain correlations included associations of ultrasonic vocalization parameters with glucose metabolism indices in locus coeruleus and substantia nigra.

CONCLUSION

FDG PET reveals abnormalities in relative regional brain glucose metabolism in rats in brain regions that are important to cognition, vocalization, and limb motor control that are also impacted by Parkinson disease. This method may be useful for mechanistic studies of behavioral deficits and therapeutic interventions in translational studies in the PD model.

摘要

引言

帕金森病（PD）是一种影响多个感觉运动和认知系统的神经退行性疾病。大鼠模型表现出特发性帕金森病中出现的发声、认知和肢体使用缺陷。我们试图测量和野生型（WT）大鼠脑区的葡萄糖代谢，并将其与超声发声、认知和肢体使用行为的测量结果相关联。

方法

（n = 12）和WT（n = 14）大鼠在约10个月龄时采用[F]氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）进行重复测量设计成像，并在6周后再次成像。通过全脑标准化FDG摄取量对相对区域葡萄糖代谢进行索引，该摄取量是针对确定用于比较的18个区域计算得出的。行为测量包括通过超声发声进行沟通的测试、使用5选串行反应时测试（5-CSRTT）进行的认知测试以及使用圆柱体测试和挑战梁进行的肢体使用测试。

结果

与WT对照组相比，大鼠在前边缘区、纹状体、疑核、苍白球和顶叶后联合皮质的相对葡萄糖代谢存在显著差异。对于行为测量，-/-大鼠发声更安静，频率范围受限，并且在肢体运动测试中表现出更多的足部失误和后肢步幅（拖曳）增加。显著的行为与脑相关性包括超声发声参数与蓝斑和黑质中葡萄糖代谢指数的关联。

结论

FDG PET显示大鼠在对认知、发声和肢体运动控制很重要且也受帕金森病影响的脑区中，相对区域脑葡萄糖代谢存在异常。该方法可能有助于在帕金森病模型的转化研究中对行为缺陷和治疗干预进行机制研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42da/11520326/c618ef0b8b0f/fnins-18-1451118-g012.jpg
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Vocal and tongue exercise in early to mid-stage Parkinson disease using the Pink1-/- rat.
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