Targeted disruption of the PEPT2 gene markedly reduces dipeptide uptake in choroid plexus.
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The presence of multiple oligopeptide transporters in brain has generated considerable interest as to their physiological role in neuropeptide homeostasis, pharmacologic importance, and potential as a target for drug delivery through the blood-brain and blood-cerebrospinal fluid barriers. To understand further the purpose of specific peptide transporters in brain, we have generated PEPT2-deficient mice by targeted gene disruption. Homozygous PepT2 null mice lacked expression of PEPT2 mRNA and protein in choroid plexus and kidney, tissues in which PepT2 is normally expressed, whereas heterozygous mice displayed PepT2 expression levels that were intermediate between those of wild-type and homozygous null animals. Mutant PepT2 null mice were found to be viable, grew to normal size and weight, and were without obvious kidney or brain abnormalities. Notwithstanding the lack of apparent biological effects, the proton-stimulated uptake of 1.9 microm glycylsarcosine (a model, hydrolysis-resistant dipeptide) in isolated choroid plexus was essentially ablated (i.e. residual activity of 10.9 and 3.9% at 5 and 30 min, respectively). These novel findings provide strong evidence that, under the experimental conditions of this study, PEPT2 is the primary member of the peptide transporter family responsible for dipeptide uptake in choroid plexus tissue. (+info)
Clinically significant persistence and enlargement of an antenatally diagnosed isolated choroid plexus cyst.
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Isolated choroid plexus cysts are usually diagnosed at the time of screening ultrasonography during the second trimester. While they raise the question of underlying chromosomal abnormalities, their clinical course is almost invariably benign with complete resolution often by the third trimester. We report the highly unusual case of a choroid plexus cyst diagnosed at 14 weeks of gestational age with subsequent further enlargement of the cyst, necessitating postpartum neurosurgical intervention. (+info)
Expression of aquaporin 1 and aquaporin 4 water channels in rat choroid plexus.
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The role of aquaporins in cerebrospinal fluid (CSF) secretion was investigated in this study. Western analysis and immunocytochemistry were used to examine the expression of aquaporin 1 (AQP1) and aquaporin 4 (AQP4) in the rat choroid plexus epithelium. Western analyses were performed on a membrane fraction that was enriched in Na(+)/K(+)-ATPase and AE2, marker proteins for the apical and basolateral membranes of the choroid plexus epithelium, respectively. The AQP1 antibody detected peptides with molecular masses of 27 and 32 kDa in fourth and lateral ventricle choroid plexus. A single peptide of 29 kDa was identified by the AQP4 antibody in fourth and lateral ventricle choroid plexus. Immunocytochemistry demonstrated that AQP1 is expressed in the apical membrane of both lateral and fourth ventricle choroid plexus epithelial cells. The immunofluorescence signal with the AQP4 antibody was diffusely distributed throughout the cytoplasm, and there was no evidence for AQP4 expression in either the apical or basolateral membrane of the epithelial cells. The data suggest that AQP1 contributes to water transport across the apical membrane of the choroid plexus epithelium during CSF secretion. The route by which water crosses the basolateral membrane, however, remains to be determined. (+info)
Spatial and temporal expression of folate-binding protein 1 (Fbp1) is closely associated with anterior neural tube closure in mice.
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Periconceptional folate supplementation is widely believed to have significant preventive effects on the production of neural tube defects. Folate-binding protein 1 (FBP1) is one of the membrane proteins that mediate cellular uptake of folate. Although recent studies suggest that Fbp1 is essential for neural tube closure, the pattern of Fbp1 expression in embryonic tissues has not been examined in detail. To elucidate how Fbp1 contributes to neural tube closure, we examined the spatial and temporal expression patterns of Fbp1 in the developing neural folds and tube of mouse embryos by in situ hybridization. Fbp1 showed a distinct expression pattern in the neural folds, which preceded initiation of neural tube closure at the cervical region and the prosencephalic/mesencephalic boundary. Fbp1 expression was mainly localized to the most dorsal regions of the neural folds where fusion was to occur. With proceeding of neural fold fusion, Fbp1 expression extended to the adjacent unfused neural folds. In the rhombencephalon, robust expression of Fbp1 was observed in rhombomere2 (r2) and r6, suggesting its roles in development of neural crest cells. Fbp1 also showed intense expression in the yolk sac, indicating that FBP1 may mediate transferring maternal folate to embryos during neurulation. These findings indicate close association between Fbp1 and anterior neural tube closure. (+info)
Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin.
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Neurogenesis occurs in the olfactory system of the adult brain throughout life, in both invertebrates and vertebrates, but its physiological regulation is not understood. We show that the production of neuronal progenitors is stimulated in the forebrain subventricular zone of female mice during pregnancy and that this effect is mediated by the hormone prolactin. The progenitors then migrate to produce new olfactory interneurons, a process likely to be important for maternal behavior, because olfactory discrimination is critical for recognition and rearing of offspring. Neurogenesis occurs even in females that mate with sterile males. These findings imply that forebrain olfactory neurogenesis may contribute to adaptive behaviors in mating and pregnancy. (+info)
Angiographic dilatation and branch extension of the anterior choroidal and posterior communicating arteries are predictors of hemorrhage in adult moyamoya patients.
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BACKGROUND AND PURPOSE: The cause of intracranial bleeding in moyamoya disease patients is still unknown. To identify factors that contribute to bleeding, we assessed the angiographic findings of moyamoya disease patients. METHODS: We examined angiograms obtained from 107 moyamoya patients; 70 manifested ischemic and 37 had hemorrhagic lesions. Patients with intracerebral aneurysms or both hemorrhagic and ischemic lesions in the same cerebral hemisphere were not included. Patients were divided into those <20 years of age (n=47) and those > or =20 years of age (n=60). The right and left hemispheres in each patient were individually classified as hemorrhagic, ischemic, or asymptomatic. Each hemisphere was assessed for dilatation and branch extension of the anterior choroidal artery (AChA) and posterior communicating artery (P-CoM) and for the degree of proliferation of basal moyamoya vessels. These data were then statistically analyzed for correlation with intracranial bleeding events. RESULTS: The degree of proliferation of basal moyamoya vessels was not statistically correlated with hemorrhagic events. On the other hand, there was a correlation between hemorrhage and dilatation and abnormal branching of the AChA. In 27 of 37 hemorrhagic hemispheres (73.0%), this artery was dilated, and its abnormal branches served as collateral supply vessels to other regions. This phenomenon was observed in 4 of 5 hemorrhagic hemispheres from young patients; it was noted in fewer than one third of ischemic and asymptomatic hemispheres from this age group. Similarly, 71.9% of hemorrhagic hemispheres from adult patients manifested AChA dilatation and branching, and the difference between hemorrhagic hemispheres and those that were ischemic or asymptomatic was statistically significant (P<0.01). Although the incidence of dilatation and abnormal branching of the P-CoM was relatively low in hemorrhagic hemispheres from adult patients (18.8%), it was significantly higher than in the ischemic and asymptomatic hemispheres from this age group. Using dilatation and abnormal branching of the AChA and/or P-CoM as assessment criteria, we obtained high specificity (86.4%) and sensitivity (84.4%) for hemorrhagic events in adult moyamoya patients. CONCLUSIONS: In adult moyamoya patients, dilatation and abnormal branching of the AChA and/or P-CoM are strong predictors of hemorrhagic events. (+info)
Transcortical transchoroidal fissure approach for ruptured distal posterior cerebral artery (P2-P3 junction) aneurysm associated with packed intraventricular hemorrhage--two case reports.
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A 56-year-old man with ruptured right P2-P3 junction aneurysm and a 66-year-old man with ruptured left P2-P3 junction aneurysm of the posterior cerebral artery associated with acute-stage packed intraventricular hemorrhage. The aneurysms were successfully clipped through the transcortical transchoroidal fissure approach. This approach requires less retraction of the temporal lobe, provides a wider surgical field, and the P2 segment can be easily reached. The present approach is very useful for the treatment of ruptured aneurysms at the P2-P3 junction, in particular for acute stage surgery associated with packed intraventricular hemorrhage. (+info)
In vitro study of the functional expression of organic anion transporting polypeptide 3 at rat choroid plexus epithelial cells and its involvement in the cerebrospinal fluid-to-blood transport of estrone-3-sulfate.
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The cerebrospinal fluid-to-blood efflux transport of estrone-3-sulfate (E(1)S) via the blood-cerebrospinal fluid barrier (BCSFB) may play an important role in regulating E(1)S levels in the brain. Here, we investigated the efflux transport of E(1)S at the BCSFB using conditionally immortalized rat choroid plexus epithelial cells (TR-CSFB) and identified the responsible transporter. The [(3)H]E(1)S uptake by TR-CSFB cells was composed of saturable and nonsaturable components, and the K(m) and V(max) values of the saturable component were determined to be 16.8 +/- 5.1 microM and 12.3 +/- 2.3 pmol/min/mg of protein, respectively. [(3)H]E(1)S uptake was inhibited by probenecid, cholate, taurocholate, sulfobromophthalein, dehydroepiandrosterone sulfate, triiodothyronine, thyroxin, and digoxin but not by p-aminohippuric acid, gamma-aminobutyric acid, or methotrexate, suggesting the involvement of organic anion transporting polypeptide (oatp) in the uptake. Reverse transcription-polymerase chain reaction analysis revealed that oatp3 was expressed in TR-CSFB cells and isolated rat choroid plexus, although oatp1 was not detected in either. Xenopus laevis oocytes expressing oatp3 exhibited [(3)H]E(1)S uptake activity with a K(m) of 8.09 +/- 2.83 microM and V(max) of 8.02 +/- 0.87 pmol/h/oocyte. Moreover, oatp3 is localized at the brush-border membrane of choroid plexus epithelial cells. These results suggest that oatp3 is involved in the E(1)S efflux transport at the BCSFB. (+info)