Exercise protects synaptic density in a rat model of Parkinson's disease

Binda, Karina Henrique; Lillethorup, Thea Pinholt; Real, Caroline Cristiano; Bærentzen, Simone Larsen; Nielsen, Martin Skovmos; Orłowski, Dariusz; Brooks, David J.; Chacur, Marucia; Landau, Anne M.

doi:10.1016/j.expneurol.2021.113741

Cited by 21 publications

(21 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such synaptic loss is also demonstrated in other Alzheimer’s disease and PD mice models ( Toyonaga et al, 2019 ; Xiong et al, 2021 ). Our study supports the recent study’s findings with lower SV2A density within the basal ganglia as reported with PET as well as autoradiography in the 6-OHDA rat model ( Binda et al, 2021 ; Thomsen et al, 2021b ), although there are methodological differences, such as employing different kinetic models and site of injection.…”

Section: Discussionsupporting

confidence: 93%

Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease

Raval

Gudmundsen

Juhl

et al. 2021

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

Parkinson’s disease (PD) is caused by progressive neurodegeneration and characterised by motor dysfunction. Neurodegeneration of dopaminergic neurons also causes aberrations within the cortico-striato-thalamo-cortical (CSTC) circuit, which has been hypothesised to lead to non-motor symptoms such as depression. Individuals with PD have both lower synaptic density and changes in neuronal metabolic function in the basal ganglia, as measured using [11C]UCB-J and [18F]FDG positron emission tomography (PET), respectively. However, the two radioligands have not been directly compared in the same PD subject or in neurodegeneration animal models. Here, we investigate [11C]UCB-J binding and [18F]FDG uptake in the CSTC circuit following a unilateral dopaminergic lesion in rats and compare it to sham lesioned rats. Rats received either a unilateral injection of 6-hydroxydopamine (6-OHDA) or saline in the medial forebrain bundle and rostral substantia nigra (n = 4/group). After 3 weeks, all rats underwent two PET scans using [18F]FDG, followed by [11C]UCB-J on a separate day. [18F]FDG uptake and [11C]UCB-J binding were both lower in the ipsilateral striatal regions compared to the contralateral regions. Using [11C]UCB-J, we could detect an 8.7% decrease in the ipsilateral ventral midbrain, compared to a 2.9% decrease in ventral midbrain using [18F]FDG. Differential changes between hemispheres for [11C]UCB-J and [18F]FDG outcomes were also evident in the CSTC circuit’s cortical regions, especially in the orbitofrontal cortex and medial prefrontal cortex where higher synaptic density yet lower neuronal metabolic function was observed, following lesioning. In conclusion, [11C]UCB-J and [18F]FDG PET can detect divergent changes following a dopaminergic lesion in rats, especially in cortical regions that are not directly affected by the neurotoxin. These results suggest that combined [11C]UCB-J and [18F]FDG scans could yield a better picture of the heterogeneous cerebral changes in neurodegenerative disorders.

show abstract

Section: Discussionsupporting

confidence: 93%

Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease

Raval

Gudmundsen

Juhl

et al. 2021

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

show abstract

“…SV2A imaging may be useful as a tool to study the effects of treatments on alleged synaptic loss associated with neurodegenerative disorders. For example, 6-OHDA-injected parkinsonian rats subjected to treadmill exercise were found to have restored striatal and nigral [ 3 H]UCB-J binding by in vitro autoradiography ( Binda et al, 2021 ).…”

Section: Synaptic Vesicle Glycoprotein 2a and Positron Emission Tomog...mentioning

confidence: 99%

Synaptic Vesicle Glycoprotein 2A: Features and Functions

et al. 2022

View full text Add to dashboard Cite

In recent years, the field of neuroimaging dramatically moved forward by means of the expeditious development of specific radioligands of novel targets. Among these targets, the synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein of synaptic vesicles, present in all synaptic terminals, irrespective of neurotransmitter content. It is involved in key functions of neurons, focused on the regulation of neurotransmitter release. The ubiquitous expression in gray matter regions of the brain is the basis of its candidacy as a marker of synaptic density. Following the development of molecules derived from the structure of the anti-epileptic drug levetiracetam, which selectively binds to SV2A, several radiolabeled markers have been synthetized to allow the study of SV2A distribution with positron emission tomography (PET). These radioligands permit the evaluation of in vivo changes of SV2A distribution held to be a potential measure of synaptic density in physiological and pathological conditions. The use of SV2A as a biomarker of synaptic density raises important questions. Despite numerous studies over the last decades, the biological function and the expressional properties of SV2A remain poorly understood. Some functions of SV2A were claimed, but have not been fully elucidated. While the expression of SV2A is ubiquitous, stronger associations between SV2A and Υ amino butyric acid (GABA)-ergic rather than glutamatergic synapses were observed in some brain structures. A further issue is the unclear interaction between SV2A and its tracers, which reflects a need to clarify what really is detected with neuroimaging tools. Here, we summarize the current knowledge of the SV2A protein and we discuss uncertain aspects of SV2A biology and physiology. As SV2A expression is ubiquitous, but likely more strongly related to a certain type of neurotransmission in particular circumstances, a more extensive knowledge of the protein would greatly facilitate the analysis and interpretation of neuroimaging results by allowing the evaluation not only of an increase or decrease of the protein level, but also of the type of neurotransmission involved.

show abstract

“…49 animal reported that exercise is an external stimulus relative to the body, which can induce limited endogenous nerve repair mechanisms, increase axons and dendritic branches, speed up information processing, and improve performance. 49 Shin et al. 50 reported that DT activates the basal nucleus on the right side of the brain, 50 and the difficulty of secondary tasks is related to the activation of the basal nucleus region, which can optimize the ability to allocate attention and improve the ability to perform dual tasks.…”

Section: Research Results and Analysismentioning

confidence: 99%