Positron Emission Tomography Neuroimaging of [F]fluorodeoxyglucose Uptake and Related Behavior in the -/- Rat Model of Parkinson Disease

Overview

Journal Front Neurosci

Date 2024 Oct 30

PMID 39474461

Authors

Alexander K Converse

Maryann N Krasko

Denis Michael Rudisch

Charlie Lenell Lunaris

Alex F Nisbet

Maxim S Slesarev

John C Szot

Andrew G Hoerst

Glen E Leverson

Catherine L Gallagher

Michelle R Ciucci

Affiliations

Soon will be listed here.

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.

References

Ho A, Bradshaw J, Iansek R . For better or worse: The effect of levodopa on speech in Parkinson's disease. Mov Disord. 2008; 23(4):574-80. DOI: 10.1002/mds.21899. View

Robbins T . The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berl). 2002; 163(3-4):362-80. DOI: 10.1007/s00213-002-1154-7. View

Dunn L, Allen G, Mamais A, Ling H, Li A, Duberley K . Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease. Neurobiol Aging. 2013; 35(5):1111-5. PMC: 3969149. DOI: 10.1016/j.neurobiolaging.2013.11.001. View

Real C, Binda K, Thomsen M, Lillethorup T, Brooks D, Landau A . Selecting the Best Animal Model of Parkinson's Disease for Your Research Purpose: Insight from PET Imaging Studies. Curr Neuropharmacol. 2023; 21(5):1241-1272. PMC: 10286593. DOI: 10.2174/1570159X21666230216101659. View

Antony P, Diederich N, Kruger R, Balling R . The hallmarks of Parkinson's disease. FEBS J. 2013; 280(23):5981-93. DOI: 10.1111/febs.12335. View

Lancelot S, Zimmer L . Small-animal positron emission tomography as a tool for neuropharmacology. Trends Pharmacol Sci. 2010; 31(9):411-7. DOI: 10.1016/j.tips.2010.06.002. View

Meles S, Renken R, Pagani M, Teune L, Arnaldi D, Morbelli S . Abnormal pattern of brain glucose metabolism in Parkinson's disease: replication in three European cohorts. Eur J Nucl Med Mol Imaging. 2019; 47(2):437-450. PMC: 6974499. DOI: 10.1007/s00259-019-04570-7. View

Brudzynski S . Biological Functions of Rat Ultrasonic Vocalizations, Arousal Mechanisms, and Call Initiation. Brain Sci. 2021; 11(5). PMC: 8150717. DOI: 10.3390/brainsci11050605. View

Wright J, Gourdon J, Clarke P . Identification of multiple call categories within the rich repertoire of adult rat 50-kHz ultrasonic vocalizations: effects of amphetamine and social context. Psychopharmacology (Berl). 2010; 211(1):1-13. DOI: 10.1007/s00213-010-1859-y. View

10.

Soto I, Nejtek V, Siderovski D, Salvatore M . PINK1 knockout rats show premotor cognitive deficits measured through a complex maze. Front Neurosci. 2024; 18:1390215. PMC: 11137248. DOI: 10.3389/fnins.2024.1390215. View

11.

Teune L, Renken R, de Jong B, Willemsen A, van Osch M, Roerdink J . Parkinson's disease-related perfusion and glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET imaging. Neuroimage Clin. 2014; 5:240-4. PMC: 4110884. DOI: 10.1016/j.nicl.2014.06.007. View

12.

Coon E, Cutsforth-Gregory J, Benarroch E . Neuropathology of autonomic dysfunction in synucleinopathies. Mov Disord. 2018; 33(3):349-358. DOI: 10.1002/mds.27186. View

13.

Aarsland D, Creese B, Politis M, Chaudhuri K, Ffytche D, Weintraub D . Cognitive decline in Parkinson disease. Nat Rev Neurol. 2017; 13(4):217-231. PMC: 5643027. DOI: 10.1038/nrneurol.2017.27. View

14.

Cullins M, Lenell C, Ciucci M, Connor N . Changes in ultrasonic vocalizations after unilateral cerebral ischemia in a rat stroke model. Behav Brain Res. 2022; 439:114252. PMC: 9795729. DOI: 10.1016/j.bbr.2022.114252. View

15.

Pietro D, Olivares A, Comini L, Vezzadini G, Luisa A, Petrolati A . Voice Alterations, Dysarthria, and Respiratory Derangements in Patients With Parkinson's Disease. J Speech Lang Hear Res. 2022; 65(10):3749-3757. DOI: 10.1044/2022_JSLHR-21-00539. View

16.

Ko J, Lerner R, Eidelberg D . Effects of levodopa on regional cerebral metabolism and blood flow. Mov Disord. 2014; 30(1):54-63. PMC: 4314428. DOI: 10.1002/mds.26041. View

17.

Asinof S, Paine T . The 5-choice serial reaction time task: a task of attention and impulse control for rodents. J Vis Exp. 2014; (90):e51574. PMC: 6592595. DOI: 10.3791/51574. View

18.

OCallaghan C, Lewis S . Cognition in Parkinson's Disease. Int Rev Neurobiol. 2017; 133:557-583. DOI: 10.1016/bs.irn.2017.05.002. View

19.

Krasko M, Hoffmeister J, Schaen-Heacock N, Welsch J, Kelm-Nelson C, Ciucci M . Rat Models of Vocal Deficits in Parkinson's Disease. Brain Sci. 2021; 11(7). PMC: 8303338. DOI: 10.3390/brainsci11070925. View

20.

Stepp C . Relative fundamental frequency during vocal onset and offset in older speakers with and without Parkinson's disease. J Acoust Soc Am. 2013; 133(3):1637-43. PMC: 3606308. DOI: 10.1121/1.4776207. View