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Article Dans Une Revue Journal of Neuroscience Année : 2012

Reactive Astrocytes Overexpress TSPO and Are Detected by TSPO Positron Emission Tomography Imaging

Vincent Lebon
  • Fonction : Auteur

Résumé

Astrocytes and microglia become reactive under most brain pathological conditions, making this neuroinflammation process a surrogate marker of neuronal dysfunction. Neuroinflammation is associated with increased levels of translocator protein 18 kDa (TSPO) and binding sites for TSPO ligands. Positron emission tomography (PET) imaging of TSPO is thus commonly used to monitor neuroinflammation in preclinical and clinical studies. It is widely considered that TSPO PET signal reveals reactive microglia, although a few studies suggested a potential contribution of reactive astrocytes. Because astrocytes and microglia play very different roles, it is crucial to determine whether reactive astro-cytes can also overexpress TSPO and yield to a detectable TSPO PET signal in vivo. We used a model of selective astrocyte activation through lentiviral gene transfer of the cytokine ciliary neurotrophic factor (CNTF) into the rat striatum, in the absence of neurodegeneration. CNTF induced an extensive activation of astrocytes, which overexpressed GFAP and become hypertrophic, whereas microglia displayed minimal increaseinreactivemarkers.TwoTSPOradioligands,[ 18 F]DPA-714[N,N-diethyl-2-(2-(4-(2-[ 18 F]fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide] The volume of radioligand binding matched the GFAP immunopositive volume. TSPO mRNA levels were significantly increased, and TSPO protein was overexpressed by CNTF-activated astrocytes. We show that reactive astrocytes overexpress TSPO, yielding to a significant and selective binding of TSPO radioligands. Therefore, caution must be used when interpreting TSPO PET imaging in animals or patients because reactive astrocytes can contribute to the signal in addition to reactive microglia.
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hal-02110993 , version 1 (17-05-2019)

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Sonia Lavisse, Martine Guillermier, Anne-Sophie Herard, Fanny Petit, Marion Delahaye, et al.. Reactive Astrocytes Overexpress TSPO and Are Detected by TSPO Positron Emission Tomography Imaging. Journal of Neuroscience, 2012, 32 (32), pp.10809-10818. ⟨10.1523/JNEUROSCI.1487-12.2012⟩. ⟨hal-02110993⟩
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