Decreased blood-brain barrier P-glycoprotein function in the progression of Parkinson’s disease, PSP and MSA. J Neural Transm

Department of Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Journal of Neural Transmission (Impact Factor: 2.4). 08/2008; 115(7):1001-9. DOI: 10.1007/s00702-008-0030-y
Source: PubMed


Decreased blood-brain barrier (BBB) efflux function of the P-glycoprotein (P-gp) transport system could facilitate the accumulation of toxic compounds in the brain, increasing the risk of neurodegenerative pathology such as Parkinson's disease (PD). This study investigated in vivo BBB P-gp function in patients with parkinsonian neurodegenerative syndromes, using [11C]-verapamil PET in PD, PSP and MSA patients. Regional differences in distribution volume were studied using SPM with higher uptake interpreted as reduced P-gp function. Advanced PD patients and PSP patients had increased [11C]-verapamil uptake in frontal white matter regions compared to controls; while de novo PD patients showed lower uptake in midbrain and frontal regions. PSP and MSA patients had increased uptake in the basal ganglia. Decreased BBB P-gp function seems a late event in neurodegenerative disorders, and could enhance continuous neurodegeneration. Lower [11C]-verapamil uptake in midbrain and frontal regions of de novo PD patients could indicate a regional up-regulation of P-gp function.

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Available from: Anna L Bartels
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    • "Similarly, various toxin-induced PD models have shown BBB disruption, including 6-OHDA treated rats and MPTP-treated mice (Carvey et al., 2005; Chen et al., 2008). On the other hand, a growing body of evidence has shown the importance of ABC multidrug transporters such as P-gp in BBB disruption (Kortekaas et al., 2005; Bartels et al., 2008; Bartels, 2011). In this aspect, KO mice for P-glycoprotein have shown an increased accumulation of neurotoxin ivermectin and the carcinostatic drug vinblanstine in the brain, suggesting the importance of P-glycoprotein in the clearance of toxic substances and a possible BBB disruption in PD (Schinkel et al., 1994). "
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    • "Another common strategy is to induce Treg (regulatory T cells)/tolerance. Indeed, Treg transfer into MPTP-treated animals attenuated loss of nigral DA neurons [84, 85]. Of particular interest is the stem cell transplant therapy. "
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    • "One of the first in vivo pieces of evidence was provided by Bartels and colleagues in an investigation of ABC transporter function in patients with neurodegenerative syndromes: PD, progressive supranuclear palsy (PSP), and multi-system atrophy (MSA), which are characterized by accumulation of aSyn or Tau (Bartels et al., 2008b). These disorders were examined by positron-emission tomography (PET) using an ABC transporter-specific probe, [ 11 C]verapamil , that is exported exclusively by ABCB1 (Bartels et al., 2008b). They demonstrated a specific accumulation of the radioprobe in brain regions where these diseases primarily start, e.g. "
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