Browsing by Author "Vergote, J"

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    Decreased vesicular acetylcholine transporter and α4β2 nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning
    (Elsevier, 2007-03-26) Quinlivan, M; Chalon, S; Vergote, J; Henderson, J; Katsifis, A; Kassiou, M; Guilloteau, D
    Degeneration of cholinergic neurons is a well known characteristic of Alzheimer's disease (AD). Two radioligands were studied in a rat model of cholinergic degeneration to evaluate their potential efficacy for molecular imaging of AD. Following specific cholinergic-cell immunolesioning with 192 IgG-saporin (SAP), ex vivo autoradiography was performed with 123IBVM, a radioligand which targets the vesicular acetylcholine transporter (VAChT). Following the decay of 123I, the same animals had in vitro autoradiography performed with 125I-A-85380, a marker for nicotinic acetylcholine receptors (nAChRs). As expected significant, widespread decreases in 123IBVM uptake were observed in SAP treated animals. Moderate but significant reductions in 125I-A-85380 binding in the hippocampus (Hip) and cerebellum (Cbm) were also observed following SAP immunolesioning. The results with 123IBVM confirm and extend previous work investigating the uptake of radioiodinated IBVM in this animal model. The results with 125I-A-85380 are unique and are in contrast with work performed in this animal model with other nAChR radioligands, indicating the favourable properties of this radioligand for molecular imaging. © 2006 Elsevier Ireland Ltd.
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    Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation
    (Springer Nature, 2008-06-07) Arlicot, N; Katsifis, A; Garreau, L; Mattner, F; Vergote, J; Duval, S; Bodard, S; Guilloteau, D; Chalon, S
    The translocator protein (TSPO; 18 kDa), the new name of the peripheral-type benzodiazepine receptor, is localised in mitochondria of glial cells and expressed in very low concentrations in normal brain. Their expression rises after microglial activation following brain injury. Accordingly, TSPO are potential targets to evaluate neuroinflammatory changes in a variety of CNS disorders. To date, only a few effective tools are available to explore TSPO by SPECT. We characterised here 6-chloro-2-(4'iodophenyl)-3-(N,N-diethyl) -imidazo[1,2-a]pyridine-3-acetamide or CLINDE in a rat model with different stages of excitotoxic lesion. Excitotoxicity was induced in male Wistar rats by unilateral intrastriatal injection of different amounts of quinolinic acid (75, 150 or 300 nmol). Six days later, two groups of rats (n = 5-6/group) were i.v. injected with [125I]-CLINDE (0.4 MBq); one group being pre-injected with PK11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography, in vitro autoradiography ([3H]-PK11195) and immunohistochemical studies (OX-42) were performed on brain sections. In the control group, [125I]-CLINDE binding was significantly higher (p < 0.001) in lesioned than that in intact side. This binding disappeared in rats pre-treated with PK11195 (p<0.001), showing specific binding of CLINDE to TSPO. Ex vivo and in vitro autoradiographic studies and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated microglia. Regression analysis yielded a positive relation between the ligand binding and the degree of neuroinflammation. These results demonstrate that CLINDE is suitable for TSPO in vivo SPECT imaging to explore their involvement in neurodegenerative disorders associated with microglial activation. © 2008 Springer International Publishing