Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis

Gallus, Marco; Roll, Wolfgang; Dik, Andre; Barca, Cristina; Zinnhardt, Bastian; Hicking, Gordon; Mueller, Christoph; Naik, Venu Narayanan; Anstötz, Max; Krämer, Julia; Rolfes, Leoni; Wachsmuth, Lydia; Pitsch, Julika; Loo, Karen M.J. van; Räuber, Saskia; Okada, Hideho; Wimberley, Catriona; Strippel, Christine; Golombeck, Kristin S.; Johnen, Andreas; Kovač, Stjepana; Groß, Catharina C.; Backhaus, Philipp; Seifert, Robert; Lewerenz, Jan; Surges, Rainer; Elger, C. E.; Wiendl, Heinz; Ruck, Tobias; Becker, Albert; Faber, Cornelius; Bauer, Jan; Meuth, Sven G.; Schaefers, Michael; Melzer, Nico

doi:10.1126/sciadv.abq7595

Cited by 7 publications

(10 citation statements)

References 88 publications

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“…OFT is often used to analyze the exploratory activity of mice [ 41 ]. The open-field apparatus was a white opaque acrylic box consisting of a 50 cm length × 50 cm width floor and four 25-cm-high walls.…”

Section: Methodsmentioning

confidence: 99%

Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer’s disease

Qi,

Chen,

Wang

et al. 2024

Transl Neurodegener

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Background Microglia-mediated neuroinflammation in Alzheimer’s disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD. Methods Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining. Results A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aβ plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD. Conclusions The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD.

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Section: Methodsmentioning

confidence: 99%

Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer’s disease

Qi,

Chen,

Wang

et al. 2024

Transl Neurodegener

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“…3D T1-weighted MR images were processed with Freesurfer ( http://surfer.nmr.mgh.harvard.edu/ ), as previously described [ 11 ]. Relative volume of hippocampus and amygdala to intracerebral volume were used for further analysis.…”

Section: Dear Sirsmentioning

confidence: 99%

“…After coregistration with segmented T1-weighted MR images, regional standardized uptake value ratio (SUVR) of the [ 18 F]DPA-714 PET were extracted, using the cerebellar grey matter as reference region [ 11 ].…”

Section: Dear Sirsmentioning

confidence: 99%

“…Sections from control (Autopsy brain from male, 71 years without neurological disease) and two different ALE patients with identical AAB (LGI1, CASPR2) were stained for TSPO as previously described using anti-TSPO (Abcam, ab109497, 1:1.000) antibodies [ 11 ].…”

Section: Dear Sirsmentioning

confidence: 99%

“…Multiplex immunofluorescent labeling was performed with antibodies against TSPO (Abcam, ab109497, 1:10.000), neurons (NeuN; Merck MAB377, 1:2500), oligodendrocytes [ 12 ] (TPPP/p25 (1:5000, kind gift from Romana Höftberger), astrocytes (GFAP, Thermo Scient. #MS-1376, 1:1000), and microglia/macrophages (Iba-1, Wako #019–19741, 1:10.000) by utilizing the Akoya Fluorescent Multiplex kit according to the manufacturer’s protocol [ 11 ].…”

Section: Dear Sirsmentioning

confidence: 99%

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[18F]DPA-714-PET-MRI reveals pronounced innate immunity in human anti-LGI1 and anti-CASPR2 limbic encephalitis

Roll,

Bauer,

Dik

et al. 2024

J Neurol

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Direct Visualization of Chemically Resolved Multilayered Domains in Mixed‐Linker Metal–Organic Frameworks

Centrone

Lerma‐Berlanga

Biacchi

et al. 2023

Adv Funct Materials

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The modular synthesis approach for assembling inorganic nodes and organic multidentate linkers into reticular solids enables rational engineering in porous materials known as metal–organic frameworks (MOFs). Incorporation of two or more linker types in MOF crystals holds great potential for engineering complex pore functionalities, by virtue of chemically heterogeneous domains. However, deciphering linkers distributions in MOFs crystals is challenging because of the insufficient spatial resolution of conventional, chemically sensitive techniques hinders the verification of rational design. Herein, the high spatial resolution and chemical specificity of infrared nanoscopy is leveraged in combination with high‐throughput diffraction‐limited hyperspectral photoluminescence imaging to determine the composition of individual multivariate UiO‐68 MOF crystals (UiO, Universitetet‐i‐Oslo), after linker‐exchange with optically active tetrazine units. The results reveal that the crystals display a three‐layer onion‐like structure composed of a core‐rich in the parent linker, an intermediate multivariate layer with a gradient in linker composition and a proto‐MOF external shell. In this outer layer, a fraction of the linkers’ binding groups is hydrogen bonded rather than coordinated with metal nodes, suggestive of superficial reconstruction during the linker‐exchange. This study advances the analytical capabilities for studying and engineering heterogeneous domains in mixed‐linker MOF crystals down to the nanoscale.

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Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis

Cited by 7 publications

References 88 publications

Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer’s disease

Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer’s disease

[18F]DPA-714-PET-MRI reveals pronounced innate immunity in human anti-LGI1 and anti-CASPR2 limbic encephalitis

Direct Visualization of Chemically Resolved Multilayered Domains in Mixed‐Linker Metal–Organic Frameworks

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