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000289316 1001_ $$aChasseigneaux, Stéphanie$$b0
000289316 245__ $$aFasting upregulates the monocarboxylate transporter MCT1 at the rat blood-brain barrier through PPAR δ activation.
000289316 260__ $$aLondon$$bBioMed Central$$c2024
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000289316 520__ $$aThe blood-brain barrier (BBB) is pivotal for the maintenance of brain homeostasis and it strictly regulates the cerebral transport of a wide range of endogenous compounds and drugs. While fasting is increasingly recognized as a potential therapeutic intervention in neurology and psychiatry, its impact upon the BBB has not been studied. This study was designed to assess the global impact of fasting upon the repertoire of BBB transporters.We used a combination of in vivo and in vitro experiments to assess the response of the brain endothelium in male rats that were fed ad libitum or fasted for one to three days. Brain endothelial cells were acutely purified and transcriptionaly profiled using RNA-Seq. Isolated brain microvessels were used to assess the protein expression of selected BBB transporters through western blot. The molecular mechanisms involved in the adaptation to fasting were investigated in primary cultured rat brain endothelial cells. MCT1 activity was probed by in situ brain perfusion.Fasting did not change the expression of the main drug efflux ATP-binding cassette transporters or P-glycoprotein activity at the BBB but modulated a restrictive set of solute carrier transporters. These included the ketone bodies transporter MCT1, which is pivotal for the brain adaptation to fasting. Our findings in vivo suggested that PPAR δ, a major lipid sensor, was selectively activated in brain endothelial cells in response to fasting. This was confirmed in vitro where pharmacological agonists and free fatty acids selectively activated PPAR δ, resulting in the upregulation of MCT1 expression. Moreover, dosing rats with a specific PPAR δ antagonist blocked the upregulation of MCT1 expression and activity induced by fasting.Altogether, our study shows that fasting affects a selected set of BBB transporters which does not include the main drug efflux transporters. Moreover, we describe a previously unknown selective adaptive response of the brain vasculature to fasting which involves PPAR δ and is responsible for the up-regulation of MCT1 expression and activity. Our study opens new perspectives for the metabolic manipulation of the BBB in the healthy or diseased brain.
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000289316 650_7 $$2Other$$aBlood-brain barrier
000289316 650_7 $$2Other$$aEndothelial cells
000289316 650_7 $$2Other$$aFasting
000289316 650_7 $$2Other$$aMCT1
000289316 650_7 $$2Other$$aPPAR δ
000289316 7001_ $$aCochois-Guégan, Véronique$$b1
000289316 7001_ $$aLecorgne, Lucas$$b2
000289316 7001_ $$aLochus, Murielle$$b3
000289316 7001_ $$aNicolic, Sophie$$b4
000289316 7001_ $$aBlugeon, Corinne$$b5
000289316 7001_ $$aJourdren, Laurent$$b6
000289316 7001_ $$0P:(DE-He78)4569ef2919d2438765ad71515f53646b$$aGomez-Zepeda, David$$b7$$udkfz
000289316 7001_ $$0P:(DE-He78)74e391c68d7926be83d679f3d8891e33$$aTenzer, Stefan$$b8$$udkfz
000289316 7001_ $$aSanquer, Sylvia$$b9
000289316 7001_ $$aNivet-Antoine, Valérie$$b10
000289316 7001_ $$aMenet, Marie-Claude$$b11
000289316 7001_ $$aLaplanche, Jean-Louis$$b12
000289316 7001_ $$aDeclèves, Xavier$$b13
000289316 7001_ $$aCisternino, Salvatore$$b14
000289316 7001_ $$aSaubaméa, Bruno$$b15
000289316 773__ $$0PERI:(DE-600)2595406-4$$a10.1186/s12987-024-00526-8$$gVol. 21, no. 1, p. 33$$n1$$p33$$tFluids and barriers of the CNS$$v21$$x1743-8454$$y2024
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