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Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary.

ABSTRACT: ATP-binding cassette (ABC) transporters play an increasing role in the understanding of pathologic peptide deposition in neurodegenerative diseases (NDs), such as Alzheimer's and Parkinson's. To describe the location of the most important ABC transporters for NDs in human brain tissue, we investigated ABCB1 and ABCC1 immunohistologically in the adult human brain and pituitary. Both transporters have similar but not identical expression patterns. In brain regions with an established blood-brain barrier (BBB), ABCB1 and ABCC1 were ubiquitously expressed in endothelial cells of the microvasculature and in a subset of larger blood vessels (mostly venules). Remarkably, both transporters were also found in fenestrated capillaries in circumventricular organs where the BBB is absent. Moreover, ABCB1 and ABCC1 were also expressed in various non-endothelia cells such as pericytes, astrocytes, choroid plexus epithelia, ventricle ependymal cells, and neurons. With regard to their neuronal expression it was shown that both transporters are located in specific nerve cell populations, which are also immunopositive for three putative cell markers of purinergic cell signalling, namely 5'-nucleotidase, adenosine deaminase and nucleoside triphosphate diphosphohydrolase-2. Therefore, we speculate that neuronal expression of ABCB1 and ABCC1 might be linked to adenosinergic/purinergic neuromodulation. Lastly, both transporters were observed in multiple adenohypophyseal cells.

SUBMITTER: Bernstein HG

PROVIDER: S-EPMC4310818 | biostudies-literature | 2014 Nov-Dec

REPOSITORIES: biostudies-literature

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Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary.

Bernstein Hans-Gert HG Hölzl Gloria G Dobrowolny Henrik H Hildebrandt Jens J Trübner Kurt K Krohn Markus M Bogerts Bernhard B Pahnke Jens J

Mechanisms of ageing and development 20140910

ATP-binding cassette (ABC) transporters play an increasing role in the understanding of pathologic peptide deposition in neurodegenerative diseases (NDs), such as Alzheimer's and Parkinson's. To describe the location of the most important ABC transporters for NDs in human brain tissue, we investigated ABCB1 and ABCC1 immunohistologically in the adult human brain and pituitary. Both transporters have similar but not identical expression patterns. In brain regions with an established blood-brain b ...[more]

PMID: 25218792

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Project description:ATP-binding cassette (ABC) transporters prevent the access of pharmacological compounds to the ischemic brain, thereby impeding the efficacy of stroke therapies. ABC transporters can be deactivated by selective inhibitors, which potently increase the brain accumulation of drugs. Concerns have been raised that long-term ABC transporter deactivation may promote neuronal degeneration and, under conditions of ischemic stroke, compromise neurological recovery. To elucidate this issue, we exposed male C57BL/6 mice to transient intraluminal middle cerebral artery occlusion (MCAO) and examined the effects of the selective ABCB1 inhibitor tariquidar (8 mg/kg/day) or ABCC1 inhibitor MK-571 (10 mg/kg/day), which were administered alone or in combination with each other over up to 28 days, on neurological recovery and brain injury. Mice were sacrificed after 14, 28, or 56 days. The Clark score, RotaRod, tight rope, and open field tests revealed reproducible motor-coordination deficits in mice exposed to intraluminal MCAO, which were not influenced by ABCB1, ABCC1, or combined ABCB1 and ABCC1 deactivation. Brain volume, striatum volume, and corpus callosum thickness were not altered by ABCB1, ABCC1 or ABCB1, and ABCC1 inhibitors. Similarly, neuronal survival and reactive astrogliosis, evaluated by NeuN and GFAP immunohistochemistry in the ischemic striatum, were unchanged. Iba1 immunohistochemistry revealed no changes of the overall density of activated microglia in the ischemic striatum of ABC transporter inhibitor treated mice, but subtle changes of microglial morphology, that is, reduced microglial cell volume by ABCB1 deactivation after 14 and 28 days and reduced microglial ramification by ABCB1, ABCC1 and combined ABCB1 and ABCC1 deactivation after 56 days. Endogenous neurogenesis, assessed by BrdU incorporation analysis, was not influenced by ABCB1, ABCC1 or combined ABCB1 and ABCC1 deactivation. Taken together, this study could not detect any exacerbation of neurological deficits or brain injury after long-term ABC transporter deactivation in this preclinical stroke model.

Dataset Information

Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary.

Publications

Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary.

Similar Datasets

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