Brain Expression (brain + expression)

Distribution by Scientific Domains


Selected Abstracts


Upregulation of Brain Expression of P-Glycoprotein in MRP2-deficient TR - Rats Resembles Seizure-induced Up-regulation of This Drug Efflux Transporter in Normal Rats

EPILEPSIA, Issue 4 2007
Katrin Hoffmann
Summary:,Purpose: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood,brain barrier (BBB). MRP2 is absent in the transport-deficient (TR,) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR, rats compared with nonmutant (wild-type) Wistar rats. Methods: The expression of MRP2 and Pgp in brain and liver sections of TR, rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. Results: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR, rats. TR, rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR, rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. Conclusions: The data on TR, rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR, rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose. [source]


Conservation and expression of IQ-domain-containing calpacitin gene products (neuromodulin/GAP-43, neurogranin/RC3) in the adult and developing oscine song control system

DEVELOPMENTAL NEUROBIOLOGY, Issue 2-3 2009
David F. Clayton
Abstract Songbirds are appreciated for the insights they provide into regulated neural plasticity. Here, we describe the comparative analysis and brain expression of two gene sequences encoding probable regulators of synaptic plasticity in songbirds: neuromodulin (GAP-43) and neurogranin (RC3). Both are members of the calpacitin family and share a distinctive conserved core domain that mediates interactions between calcium, calmodulin, and protein kinase C signaling pathways. Comparative sequence analysis is consistent with known phylogenetic relationships, with songbirds most closely related to chicken and progressively more distant from mammals and fish. The C-terminus of neurogranin is different in birds and mammals, and antibodies to the protein reveal high expression in adult zebra finches in cerebellar Purkinje cells, which has not been observed in other species. RNAs for both proteins are generally abundant in the telencephalon yet markedly reduced in certain nuclei of the song control system in adult canaries and zebra finches: neuromodulin RNA is very low in RA and HVC (relative to the surrounding pallial areas), whereas neurogranin RNA is conspicuously low in Area X (relative to surrounding striatum). In both cases, this selective downregulation develops in the zebra finch during the juvenile song learning period, 25,45 days after hatching. These results suggest molecular parallels to the robust stability of the adult avian song control circuit. 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source]


Upregulation of Brain Expression of P-Glycoprotein in MRP2-deficient TR - Rats Resembles Seizure-induced Up-regulation of This Drug Efflux Transporter in Normal Rats

EPILEPSIA, Issue 4 2007
Katrin Hoffmann
Summary:,Purpose: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood,brain barrier (BBB). MRP2 is absent in the transport-deficient (TR,) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR, rats compared with nonmutant (wild-type) Wistar rats. Methods: The expression of MRP2 and Pgp in brain and liver sections of TR, rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. Results: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR, rats. TR, rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR, rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. Conclusions: The data on TR, rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR, rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose. [source]


Aquaporin 4 changes in rat brain with severe hydrocephalus

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006
Xiaoyan Mao
Abstract Hydrocephalus is characterized by impaired cerebrospinal fluid (CSF) flow with enlargement of the ventricular cavities of the brain and progressive damage to surrounding tissue. Bulk water movement is altered in these brains. We hypothesized that increased expression of aquaporins, which are water-permeable channel proteins, would occur in these brains to facilitate water shifts. We used quantitative (real-time) RT-PCR, Western blotting and immunohistochemistry to evaluate the brain expression of aquaporins (AQP) 1, 4, and 9 mRNA and protein in Sprague,Dawley rats rendered hydrocephalic by injection of kaolin into cistern magna. AQP4 mRNA was significantly up-regulated in parietal cerebrum and hippocampus 4 weeks and 9 months after induction of hydrocephalus (P < 0.05). Although Western blot analysis showed no significant change, there was more intense perivascular AQP4 immunoreactivity in cerebrum of hydrocephalic brains at 3,4 weeks after induction. We did not detect mRNA or protein changes in AQP1 (located in choroid plexus) or AQP9 (located in select neuron populations). Kir4.1, a potassium channel protein linked to water flux, exhibited enhanced immunoreactivity in the cerebral cortex of hydrocephalic rats; the perineuronal distribution was entirely different from that of AQP4. These results suggest that brain AQP4 up-regulation might be a compensatory response to maintain water homeostasis in hydrocephalus. [source]


Palatable High-Energy Diet Decreases the Expression of Cannabinoid Type 1 Receptor Messenger RNA in Specific Brain Regions in the Rat

JOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2009
E. Timofeeva
In laboratory rodents, a palatable high-energy diet (PHED) is usually consumed in a higher quantity than a standard laboratory diet, leading to the development of an obese phenotype. The central effects of PHED are not fully understood. Nonetheless, the long-term consumption of PHED can decrease cannabinoid type 1 receptor (CB1R) protein density in particular brain regions. However, little is known about the diet-dependent regulation of the brain expression of CB1R mRNA. The present study aimed to investigate the effects of the long-term consumption of PHED and short-term (12 h) food deprivation on the brain expression of CB1R mRNA. For 13 weeks, rats were fed a standard laboratory chow or PHED presented as a free choice of chow, shortcake biscuits and pork spread. In total, the food intake of PHED rats was higher than that of chow-fed animals. Expectedly, PHED rats demonstrated higher body weight than chow-fed animals. The difference in body weight between PHED- and chow-fed rats was as result of the fat but not the lean mass. PHED-fed rats had significantly higher plasma levels of leptin and insulin and significantly higher levels of expression of suppressor of cytokine signalling 3 (SOCS-3) in the arcuate hypothalamic nucleus. The long-term consumption of PHED significantly decreased the levels of CB1R mRNA expression in the cingulate (Cg) cortex, ventromedial hypothalamic nucleus and the descending/autonomic divisions of the parvocellular hypothalamic nucleus (PVH), the ventrolateral parvocellular PVH and, to a lesser extent, the dorsomedial parvocellular PVH. Acute food deprivation decreased the levels of CB1R transcript in the Cg and ventrolateral parvocellular PVH. Altogether, the present results demonstrate that long-term PHED leads to an increase in the hypothalamic expression of SOCS-3 mRNA and a decrease in expression of CB1R mRNA in the Cg cortex and specific hypothalamic regions. [source]