Mitochondrial translocator protein (TSPO) ligand attenuates neuroinflammation and reduces complement component C1Q in a mouse model of tauopathy: Nonhuman: Preclinical studies on APOE and neuroinflammation. (7th December 2020)

• Record Type: Journal Article
• Authors: Fairley, Lauren H.; Sahara, Naruhiko; Suhara, Tetsuya; Higuchi, Makoto; Barron, Anna M.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 9
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.038497
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The mitochondrial translocator protein (TSPO) has been widely investigated as a positron emission tomography (PET) detectable biomarker of neuroinflammation, as well as a potential therapeutic target for the treatment of neurodegenerative disease. In transgenic mouse models of AD, we and others have shown that TSPO ligands attenuate inflammation and beta amyloid burden (Barron et al., 2013). However, the effect of TSPO ligands on tauopathy‐induced inflammation has not yet been investigated. Here, we analysed the effects of the prototypic TSPO ligand, Ro5‐4864, on the progression of tauopathy, gliosis and atrophy in the rTg4510 tau transgenic mouse model (TauTg). Method: TauTg and WT control mice were treated with Ro5‐4864 or vehicle for 4 months. Brain atrophy was assessed using volumetric magnetic resonance imaging, while tauopathy and neuroinflammation were assessed by PET using 11 C‐PBB3 and 18 F‐FEBMP tracers, respectively. To corroborate in vivo findings, immunohistochemistry was performed in sections from scanned mice to measure phosphorylated tau (AT8), inflammation (IBA1, complement component 1q, C1q) and neuronal loss (NeuN). Result: Ro5‐4864 treatment reduced markers of neuroinflammation, as well as expression of the neuronal 'eat me' signal, C1q in rTg4510 mice. In vitro experiments using the immortalized microglial cell line, BV2, confirmed the TSPO ligands, Ro5‐4864, reduced expression of C1q in response to inflammatory stimuli. Conclusion: These findings support a protective role for TSPO ligands in reducing tauopathy‐induced neuroinflammation.