Browsing by Author "Garibotto, V"

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    Knockout of TSPO delays and reduces amyloid, Tau, astrocytosis and behavioral dysfunctions in Alzheimer’s disease
    (Cold Spring Harbor Laboratory, 2022-03-28) Ceyzériat, K; Meyer, L; Boutjelda, F; Tsartsalis, S; Amossé, Q; Middleton, RJ; Liu, GJ; Banati, RB; Zilli, T; Garibotto, V; Millet, P; Tournier, BB
    The 18kDa translocator protein (TSPO) is up-regulated in glial cells in neurodegenerative diseases. In Alzheimer’s disease (AD) animal models, TSPO is first overexpressed in astrocytes and then in microglia. However, the precise role of TSPO in the onset and progression of pathology and symptoms characteristic of the disease remains unknown. Here, we report that in the absence of TSPO in 3xTgAD mice the expected disease onset is significantly delayed and a reduction is seen in the hippocampal load of poorly and highly aggregated forms of Tau (−44% and −82%, respectively) and Aβ42 (−25% and −95%, respectively), at 9 months of age. In addition, the astrocyte reactivity was decreased in 3xTgAD.TSPO−/− mice with a reduction in the morphologic complexity and the size of astrocytes in the dorso-dorsal hippocampus and the hilus. Functionally, the absence of TSPO ameliorated the cognitive consequences of adeno-associated virus-induced Tau over-expression in the hippocampus. This suggests that TSPO plays an important role in the active disease progression of AD. TSPO-inhibiting drugs thus merit further exploration as to their potential to reduce the rate of neurodegenerative disease progression. © 2022 The Authors