| 1. |
- Nelson, Britta S., et al.
(författare)
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Escalated Alcohol Self-Administration and Sensitivity to Yohimbine-lnduced Reinstatement in Alcohol Preferring Rats: Potential Role of Neurokinin-1 Receptors in the Amygdala
- 2019
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Ingår i: Neuroscience. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4522 .- 1873-7544. ; 413, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors significantly contribute to the risk for developing alcoholism. To study these factors and other associated phenotypes, rodent lines have been developed using selective breeding for high alcohol preference. One of these models, the alcohol preferring (P) rat, has been used in hundreds of preclinical studies over the last few decades. However, very few studies have examined relapse-like behavior in this rat strain. In this study, we used operant self-administration and yohimbine-induced reinstatement models to examine relapse-like behavior in P rats. Our previous work has demonstrated that P rats show increased expression of the neurokinin-1 receptor (NK1R) in the central nucleus of the amygdala (CeA), and this functionally contributes to escalated alcohol consumption in this strain. We hypothesized that P rats would show increased sensitivity to yohimbine-induced reinstatement that is also mediated by NK1R in the CeA. Using Fos staining, site-specific infusion of NK1R antagonist, and viral vector overexpression, we examined the influence of NK1R on the sensitivity to yohimbine-induced reinstatement of alcohol seeking. We found that P rats displayed increased sensitivity to yohimbine-induced reinstatement as well as increased neuronal activation in the CeA after yohimbine injection compared to the control Wistar strain. Intra-CeA infusion of NK1R antagonist attenuates yohimbine-induced reinstatement in P rats. Conversely, upregulation of NK1R within the CeA of Wistar rats increases alcohol consumption and sensitivity to yohimbine-induced reinstatement. These findings suggest that NK1R upregulation in the CeA contributes to multiple alcohol-related phenotypes in the P rat, including alcohol consumption and sensitivity to relapse. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
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| 2. |
- Henriksson, Richard, et al.
(författare)
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PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain
- 2014
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier. - 0006-3002 .- 1878-2434. ; 1839:11, s. 1226-1232
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Tidskriftsartikel (refereegranskat)abstract
- The dynorphin κ-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders.
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| 3. |
- Vazin, Tandis, et al.
(författare)
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Limited proliferation capacity of mesencepahlic neural progenitor cells derived from human embryonic stem cells
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Midbrain neural progenitor cells (NPC) derived from human embryonic stem cells(hESC) may be useful for development of novel transplantation and gene deliverystrategies. One of the major goals of human transplantation research has been to developa means of generating dopaminergic (DA) neurons in vitro, which can be employed fortransplantation. NPC can be generated from hESC using a number of strategies. Thephenotypic conservation, stability, and differentiation of NPC generated under variousconditions are, however, not well understood. In the present study we generatedexpandable mesencephalic-restricted human NPC from the hESC line BG01V2 under theinfluence of stromal-derived inducing activity (SDIA), and assessed their capacity forproliferation and maintenance of cellular memory. The NPC could be expanded by fivefoldas neurospheres for up to 2 weeks in vitro while retaining their DA differentiationpotential, without a substantial loss of cellular memory and viability. Although cellswere continuously maintained under the influence of the midbrain patterning factors SHHand FGF8, they progressively lost their ability to differentiate to DA neurons andmaintain a stable phenotype in vitro. Preliminary transplantation experiments ofneurospheres with midbrain identity in intrastriatal 6-hydroxydopamine lesioned animalsindicated, however, that these cells could survive and conserve their phenotype in vivo.Therefore, in vitro propagation of SDIA-derived NPC under the present conditions resultsin a gradual loss of growth capacity and multipotency over time, whereas the phenotypeof transplanted NPC remains unaltered.
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