Your search for: 'author:("Farinotti, Robert")' has returned 3 results. (0.006s) Save search

Authors: Do, Tuan Minh | Bedussi, Beatrice | Chasseigneaux, Stéphanie | Dodacki, Agnès | Yapo, Cédric | Chacun, Hélène | Scherrmann, Jean-Michel | Farinotti, Robert | Bourasset, Fanchon

Article Type: Research Article

Abstract: The influx of amyloid-β peptide (Aβ) across the blood-brain barrier is partly mediated by the receptor for advanced glycation end products (RAGE). But other transporters, like Oatp (organic anion transporter polypeptide, SLC21) transporters, could also be involved. We used in situ brain perfusion to show that rosuvastatin and taurocholate, two established Oatp1a4 substrates, decreased (5-fold) the Clup of [3 H]Aβ while L-thyroxine increased it (5.5-fold). We demonstrated an interaction between Aβ and Oatp1a4 by co-immunoprecipitation and western blotting experiments, supporting the hypothesis that the rosuvastatin- and taurocholate-sensitive transporter was Oatp1a4. In conclusion, our results suggest that, in mice, the brain …uptake of Aβ is partly mediated by Oatp1a4 and that L-thyroxine may play a crucial role in the inhibition of brain Aβ clearance. Show more

Keywords: Alzheimer's disease, amyloid-β peptide, blood-brain barrier, in situ brain perfusion, L-thyroxine, Oatp1a4, rosuvastatin

DOI: 10.3233/JAD-121891

Citation: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 555-561, 2013

Authors: Do, Tuan Minh | Dodacki, Agnès | Alata, Wael | Calon, Frederic | Nicolic, Sophie | Scherrmann, Jean-Michel | Farinotti, Robert | Bourasset, Fanchon

Article Type: Research Article

Abstract: The involvement of transporters located at the blood-brain barrier (BBB) has been suggested in the control of cerebral Aβ levels, and thereby in Alzheimer’s disease (AD). However, little is known about the regulation of these transporters at the BBB in animal models of AD. In this study, we investigated the BBB expression of Aβ influx (Rage) and efflux (Abcb1-Abcg2-Abcg4-Lrp-1) transporters and cholesterol transporter (Abca1) in 3–18-month-old 3xTg-AD and control mice. The age-dependent effect of BBB transporters regulation on the brain uptake clearance (Clup ) of [3 H]cholesterol and [3 H]Aβ1 - 40 was then evaluated in these mice, using the in situ …brain perfusion technique. Our data suggest that transgenes expression led to the BBB increase in Aβ influx receptor (Rage) and decrease in efflux receptor (Lrp-1). Our data also indicate that mice have mechanisms counteracting this increased net influx. Indeed, Abcg4 and Abca1 are up regulated in 3- and 3/6-month-old 3xTg-AD mice, respectively. Our data show that the balance between the BBB influx and efflux of Aβ is maintained in 3 and 6-month-old 3xTg-AD mice, suggesting that Abcg4 and Abca1 control the efflux of Aβ through the BBB by a direct (Abcg4) or indirect (Abca1) mechanism. At 18 months, the BBB Aβ efflux is significantly increased in 3xTg-AD mice compared to controls. This could result from the significant up-regulation of both Abcg2 and Abcb1 in 3xTg-AD mice compared to control mice. Thus, age-dependent regulation of several Aβ and cholesterol transporters at the BBB could ultimately limit the brain accumulation of Aβ. Show more

Keywords: ABCA1, ABCB1, ABCG2, ABCG4, Alzheimer’s disease, amyloid-β, blood-brain barrier, cholesterol, Oatp1a4, RAGE, 3xTg-AD

DOI: 10.3233/JAD-150350

Citation: Journal of Alzheimer's Disease, vol. 49, no. 2, pp. 287-300, 2016

Authors: Do, Tuan Minh | Noel-Hudson, Marie-Sophie | Ribes, Sandy | Besengez, Capucine | Smirnova, Maria | Cisternino, Salvatore | Buyse, Marion | Calon, Frédéric | Chimini, Giovanna | Chacun, Hélène | Scherrmann, Jean-Michel | Farinotti, Robert | Bourasset, Fanchon

Article Type: Research Article

Abstract: The accumulation of amyloid-β peptide (Aβ) in the brain is a critical hallmark of Alzheimer's disease. This high cerebral Aβ concentration may be partly caused by impaired clearance of Aβ across the blood-brain barrier (BBB). The low-density lipoprotein receptor-related protein-1 (LRP-1) and the ATP-binding cassette (ABC) protein ABCB1 (P-glycoprotein) are involved in the efflux of Aβ across the BBB. We hypothesized that other ABC proteins, such as members of the G subfamily, are also involved in the BBB clearance of Aβ. We therefore investigated the roles of ABCG2 (BCRP) and ABCG4 in the efflux of [3 H] Aβ1-40 from HEK293 …cells stably transfected with human ABCG2 or mouse abcg4. We showed that ABCG2 and Abcg4 mediate the cellular efflux of [3 H] Aβ1-40 . In addition, probucol fully inhibited the efflux of [3 H] Aβ1-40 from HEK293-abcg4 cells. Using the in situ brain perfusion technique, we showed that GF120918 (dual inhibitor of Abcb1 and Abcg2) strongly enhanced the uptake (Clup , μl/g/s) of [3 H] Aβ1-40 by the brains of Abcb1-deficient mice, but not by the brains of Abcb1/Abcg2-deficient mice, suggesting that Abcg2 is involved in the transport of Aβ at the mouse BBB. Perfusing the brains of Abcb1/Abcg2- and Abca1-deficient mice with [3 H] Aβ1-40 plus probucol significantly increased the Clup of Aβ. This suggests that a probucol-sensitive transporter that is different from Abca1, Abcb1, and Abcg2 is involved in the brain efflux of Aβ. We suggest that this probucol-sensitive transporter is Abcg4. We conclude that Abcg4 acts in concert with Abcg2 to efflux Aβ from the brain across the BBB. Show more

Keywords: Abca1, Abcb1, Abcg4, Abcg2, Alzheimer's disease, amyloid-β, blood-brain barrier, in situ brain perfusion, mouse

DOI: 10.3233/JAD-2012-112189

Citation: Journal of Alzheimer's Disease, vol. 30, no. 1, pp. 155-166, 2012