TSPO PET upregulation predicts epileptic phenotype at disease onset independently from chronic TSPO expression in a rat model of temporal lobe epilepsy

Bertoglio, Daniele; Amhaoul, Halima; Goossens, Joery; Ali, Idrish; Jonckers, Elisabeth; Bijnens, Tom; Siano, Matteo; wyffels, Leonie; Verhaeghe, Jeroen; Linden, Annemie Van der; Staelens, Steven; Dedeurwaerdere, Stefanie

doi:10.1016/j.nicl.2021.102701

Cited by 13 publications

(8 citation statements)

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“…Many studies have been conducted to date exploring a range of preclinical imaging modalities, demonstrating the value of small-animal PET scanning in the context of neuroinflammation as a robust and quantitative approach to longitudinal noninvasive in vivo imaging. Researchers have previously employed TSPO PET imaging time series to characterize neuroinflammation associated with animal disease models of conditions including Alzheimer’s disease [ 24 ], stroke [ 25 ], seizure [ 26 ], and multiple sclerosis [ 27 ]. Despite much progress in this research space, the precise role of microglial activation in the context of MDD dynamics remains poorly understood, and there have been no previously published studies to our knowledge evaluating the use of in vivo TSPO imaging as a tool for monitoring inflammation in the brain in the context of LPS-induced depression.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Microglial Activation is Associated with LPS-induced Depressive-like Behavior in Mice: An [18F] DPA-714 PET Imaging Study

Qiu

Guo

Wang

et al. 2022

Bosn J of Basic Med Sci

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Major depressive disorder (MDD) is a highly pervasive, severe psychological condition for which the precise underlying pathophysiology is incompletely understood, although microglial activation is known to play a role in this context. In this study we analyzed the association between neuroinflammation and depressive-like behaviors in a lipopolysaccharide (LPS)-induced mouse model system using 10-12-week-old male C57BL/6 mice. Microglial activation and associated neuroinflammatory activity were monitored via positron emission tomography (PET) imaging. Animals were assessed at three time points, including 24 h prior to LPS injection, 24 h post-LPS injection, and 72 h post-LPS injection. Analyses of microglial activation and hippocampal neuroinflammation were conducted through [18]F DPA-714 PET imaging and immunohistochemical staining for ionized calcium-binding adapter molecule 1 (Iba-1) and translocator protein (TSPO). Moreover, NOD-like receptor protein 3 (NLRP3) inflammasome activity and interleukin-1β (IL-1β) levels were assessed at 24 h post-LPS injection. We found that LPS treatment was associated with a marked increase in depressive-like behavior at 24 h post-injection time point, and that it was less pronounced at the 72 h post-injection time point. These changes coincided with enhanced [18F] DPA-714 PET uptake in the whole brain, hippocampus, cortex and amygdala together with increased hippocampal microglial activation as evidenced by immunofluorescent staining. By 72 h post-injection, however, these PET and immunofluorescence phenotypes had returned to baseline levels. Furthermore, increased NLRP3 inflammasome activation and IL-1β expression were evident at 24 h post-LPS injection. These data demonstrate that dynamic microglial activation is associated with LPS-induced depressive-like behaviors and hippocampal neuroinflammation in a mouse model system.

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Section: Discussionmentioning

confidence: 99%

Dynamic Microglial Activation is Associated with LPS-induced Depressive-like Behavior in Mice: An [18F] DPA-714 PET Imaging Study

Qiu

Guo

Wang

et al. 2022

Bosn J of Basic Med Sci

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“…In the near future, it will be interesting to expand this approach to cross-species (e.g. people with HD given the reported loss of SV2A (Delva et al, 2022), as well as to other disorders known to affect SV2A, both preclinically (Bertoglio et al, 2021; Bertoglio et al, 2022a; Glorie et al, 2020) and clinically (Chen et al, 2018; Finnema et al, 2020; Holmes et al, 2019; Matuskey et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Identification of pre-synaptic density networks using SV2A PET imaging and ICA in healthy and diseased mice

Akkermans

Zajicek

Miranda

et al. 2022

Preprint

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BackgroundSynaptic vesicle glycoprotein 2A (SV2A) is a vesicle glycoprotein involved in neurotransmitter release. SV2A is located on the pre-synaptic terminals of neurons and visualized using the radioligand [11C]UCB-J and positron emission tomography (PET) imaging. Thus, SV2A PET imaging can provide a proxy for pre-synaptic density in health and disease. This study aims to apply independent component analysis (ICA) to SV2A PET data acquired in mice to identify pre-synaptic density networks (pSDNs), explore how ageing affects these pSDNs, and determine the impact of a neurological disorder on these networks.MethodsWe used [11C]UCB-J PET imaging data (n=135) available at different ages (3, 7, 10, and 16 months) in wild-type (WT) C57BL/6J mice and in diseased mice (mouse model of Huntington’s disease, HD). First, ICA was performed on a healthy dataset after it was split into two equal-sized samples (n=36 each) and the analysis was repeated 50 times in different partitions. We tested different model orders (8, 12, and 16) and identified the pSDNs. Next, we investigated the effect of age on the loading weights of the identified pSDNs. Additionally, the identified pSDNs were compared to those of diseased mice to assess the impact of disease on each pSDNs.ResultsModel order 12 resulted in the preferred choice to provide six reliable and reproducible independent components (ICs) as supported by the cluster-quality index (IQ) and regression coefficients (β) values. Temporal analysis showed age-related statistically significant changes on the loading weights in four ICs. ICA in an HD model revealed a statistically significant disease-related effect on the loading weights in several pSDNs in line with the progression of the disease.ConclusionThis study validated the use of ICA on SV2A PET data acquired with [11C]UCB-J for the identification of cerebral pre-synaptic density networks in mice in a rigorous and reproducible manner. Furthermore, we showed that different pSDNs change with age and are affected in a disease condition. These findings highlight the potential value of ICA in understanding pre-synaptic density networks in the mouse brain.

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“…With the improved sensitivity, we can obtain better image quality, or use shorter scan time or less radiation dose, or image the animal over extended time periods [19,20,[84][85][86]. Examples are fast dynamic imaging to study the time courses of a label in tissue regions of interest and in arterial blood [20], and studies of chronic inflammatory disease where the binding of translocator protein (TSPO) ligands can be low and hard to detect [87][88][89]. Another key stimulus for realizing increased sensitivity is the limitation as to the amount of tracer that can be administered of molecules that are with selectivity to specific cellular binding sites.…”

Section: The Benefits Of Total-body Small Animal Pet To Applicationsmentioning

confidence: 99%

Technical opportunities and challenges in developing total-body PET scanners for mice and rats

Jones

2023

EJNMMI Phys

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Positron emission tomography (PET) is the most sensitive in vivo molecular imaging technique available. Small animal PET has been widely used in studying pharmaceutical biodistribution and disease progression over time by imaging a wide range of biological processes. However, it remains true that almost all small animal PET studies using mouse or rat as preclinical models are either limited by the spatial resolution or the sensitivity (especially for dynamic studies), or both, reducing the quantitative accuracy and quantitative precision of the results. Total-body small animal PET scanners, which have axial lengths longer than the nose-to-anus length of the mouse/rat and can provide high sensitivity across the entire body of mouse/rat, can realize new opportunities for small animal PET. This article aims to discuss the technical opportunities and challenges in developing total-body small animal PET scanners for mice and rats.

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TSPO PET upregulation predicts epileptic phenotype at disease onset independently from chronic TSPO expression in a rat model of temporal lobe epilepsy

Abstract: Graphical abstract

Cited by 13 publications

References 56 publications

Dynamic Microglial Activation is Associated with LPS-induced Depressive-like Behavior in Mice: An [18F] DPA-714 PET Imaging Study

Dynamic Microglial Activation is Associated with LPS-induced Depressive-like Behavior in Mice: An [18F] DPA-714 PET Imaging Study

Identification of pre-synaptic density networks using SV2A PET imaging and ICA in healthy and diseased mice

Technical opportunities and challenges in developing total-body PET scanners for mice and rats

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