| 41. |
- Pickering, Chris, et al.
(författare)
-
The Adhesion GPCR GPR125 is specifically expressed in the choroid plexus and is upregulated following brain injury
- 2008
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 9, s. 97-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDGPR125 belongs to the family of Adhesion G protein-coupled receptors (GPCRs). A single copy of GPR125 was found in many vertebrate genomes. We also identified a Drosophila sequence, DmCG15744, which shares a common ancestor with the entire Group III of Adhesion GPCRs, and also contains Ig, LRR and HBD domains which were observed in mammalian GPR125.RESULTSWe found specific expression of GPR125 in cells of the choroid plexus using in situ hybridization and protein-specific antibodies and combined in situ/immunohistochemistry co-localization using cytokeratin, a marker specific for epithelial cells. Induction of inflammation by LPS did not change GPR125 expression. However, GPR125 expression was transiently increased (almost 2-fold) at 4 h after traumatic brain injury (TBI) followed by a decrease (approximately 4-fold) from 2 days onwards in the choroid plexus as well as increased expression (2-fold) in the hippocampus that was delayed until 1 day after injury.CONCLUSIONThese findings suggest that GPR125 plays a functional role in choroidal and hippocampal response to injury.
|
|
| 42. |
- Rask-Andersen, Mathias, et al.
(författare)
-
Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway
- 2011
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 12, s. 117-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Fat mass and obesity gene (FTO) has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI). However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression.Results: We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2), cAMP-dependent protein kinase catalytic subunit beta (Prkacb), Brain derived neurotrophic factor (Bdnf), neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2), Signal transducer and activator of transcription 3 (Stat3), and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation.Conclusions: Gene expression studies validate several candidates generated through database studies of possible FTO-interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein beta (C/EBP beta)
|
|
| 43. |
- Riebe, Ilse, 1978, et al.
(författare)
-
Development of synaptic connectivity onto interneurons in stratum radiatum in the CA1 region of the rat hippocampus.
- 2012
-
Ingår i: BMC neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: The impact of a given presynaptic neuron on the firing probability of the postsynaptic neuron critically depends on the number of functional release sites that connect the two neurons. One way of determining the average functional synaptic connectivity onto a postsynaptic neuron is to compare the amplitudes of action potential dependent spontaneous synaptic currents with the amplitude of the synaptic currents that are independent of action potentials ("minis"). With this method it has been found that average synaptic connectivity between glutamatergic CA3 and CA1 pyramidal cells increases from single connections in the neonatal rat, to multiple connections in the young adult rat. On the other hand, gamma-aminobutyric acid (GABA)ergic interneurons form multiple connections onto CA1 pyramidal cells already in the neonatal rat, and the degree of multiple GABAergic connectivity is preserved into adulthood. In the present study, we have examined the development of glutamate and GABA connectivity onto GABAergic CA1 stratum radiatum interneurons in the hippocampal slice, and compared this to the connectivity onto CA1 pyramidal neurons. RESULTS: In GABAergic interneurons in the CA1 stratum radiatum, irrespective of developmental stage, we found that the average amplitude of action potential dependent spontaneous AMPA receptor-mediated synaptic currents were of the same magnitude as the mini AMPA receptor mediated synaptic currents. This finding indicates that these GABAergic interneurons, in contrast to the CA1 pyramidal neurons, preserve single glutamate connectivity throughout development. For GABA connectivity, on the other hand, we found multiple functional synaptic connections onto the interneurons, as onto the pyramidal cells. CONCLUSIONS: The results presented here confirm that glutamate and GABA synaptic connectivity develop very differently in the hippocampal CA1 region. Thus, whereas average GABA connectivity is multiple throughout the development, glutamate connectivity is unitary early in development. Our results further suggest that the development of glutamate synaptic connectivity differs markedly between pyramidal cells and GABAergic interneurons in stratum radiatum, such that a given presynaptic glutamatergic cell appears not allowed to increase its connectivity onto the postsynaptic stratum radiatum interneuron, as it may do onto the postsynaptic CA1 pyramidal cell.
|
|
| 44. |
- Scholz, Birger, et al.
(författare)
-
Sex-dependent gene expression in early brain development of chicken embryos
- 2006
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 7, s. 12-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Differentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms.RESULTS:Using cDNA microarrays and real-time PCR we found gene expression differences between the male and female embryonic brain (or whole head) that may be independent of morphological differentiation of the gonads. Genes located on the sex chromosomes (ZZ in males and ZW in females) were common among the differentially expressed genes, several of which (WPKCI-8, HINT, MHM non-coding RNA) have previously been implicated in avian sex determination. A majority of the identified genes were more highly expressed in males. Three of these genes (CDK7, CCNH and BTF2-P44) encode subunits of the transcription factor IIH complex, indicating a role for this complex in neuronal differentiation.CONCLUSION:In conclusion, this study provides novel insights into sexually dimorphic gene expression in the embryonic chicken brain and its possible involvement in sex differentiation of the nervous system in birds.
|
|
| 45. |
- Sievertzon, Maria, et al.
(författare)
-
Epidermal growth factor (EGF) withdrawal masks gene expression differences in the study of pituitary adenylate cyclase-activating polypeptide (PACAP) activation of primary neural stem cell proliferation
- 2005
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 6, s. 55-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The recently discovered adult neural stem cells, which maintain continuous generation of new neuronal and glial cells throughout adulthood, are a promising and expandable source of cells for use in cell replacement therapies within the central nervous system. These cells could either be induced to proliferate and differentiate endogenously, or expanded and differentiated in culture before being transplanted into the damaged site of the brain. In order to achieve these goals effective strategies to isolate, expand and differentiate neural stem cells into the desired specific phenotypes must be developed. However, little is known as yet about the factors and mechanisms influencing these processes. It has recently been reported that pituitary adenylate cyclase-activating polypeptide (PACAP) promotes neural stem cell proliferation both in vivo and in vitro. Results: We used cDNA microarrays with the aim of analysing the transcriptional changes underlying PACAP induced proliferation of neural stem cells. The primary neural stem/progenitor cells used were neurospheres, generated from the lateral ventricle wall of the adult mouse brain. The results were compared to both differentiation and proliferation controls, which revealed an unexpected and significant differential expression relating to withdrawal of epidermal growth factor (EGF) from the neurosphere growth medium. The effect of EGF removal was so pronounced that it masked the changes in gene expression patterns produced by the addition of PACAP. Conclusion: Experimental models aiming at transcriptional analysis of induced proliferation in primary neural stem cells need to take into consideration the significant effect on transcription caused by removal of EGF. Alternatively, EGF-free culture conditions need to be developed.
|
|
| 46. |
- Ström, Jakob, et al.
(författare)
-
Disruption of the alox5ap gene ameliorates focal ischemic stroke: possible consequence of impaired leukotriene biosynthesis
- 2012
-
Ingår i: BMC Neuroscience. - London, United Kingdom : BioMed Central. - 1471-2202. ; 13, s. 146-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundLeukotrienes are potent inflammatory mediators, which in a number of studies have been found to be associated with ischemic stroke pathology: gene variants affecting leukotriene synthesis, including the FLAP (ALOX5AP) gene, have in human studies shown correlation to stroke incidence, and animal studies have demonstrated protective properties of various leukotriene-disrupting drugs. However, no study has hitherto described a significant effect of a genetic manipulation of the leukotriene system on ischemic stroke. Therefore, we decided to compare the damage from focal cerebral ischemia between wild type and FLAP knockout mice. Damage was evaluated by infarct staining and a functional test after middle cerebral artery occlusion in 20 wild type and 20 knockout male mice.ResultsMortality-adjusted median infarct size was 18.4 (3.2-76.7) mm3 in the knockout group, compared to 72.0 (16.7-174.0) mm3 in the wild type group (p < 0.0005). There was also a tendency of improved functional score in the knockout group (p = 0.068). Analysis of bone marrow cells confirmed that knockout animals had lost their ability to form leukotrienes.ConclusionsSince the local inflammatory reaction after ischemic stroke is known to contribute to the brain tissue damage, the group difference seen in the current study could be a consequence of a milder inflammatory reaction in the knockout group. Our results add evidence to the notion that leukotrienes are important in ischemic stroke, and that blocked leukotriene production ameliorates cerebral damage.
|
|
| 47. |
- Ström, Jakob, et al.
(författare)
-
Method parameters’ impact on mortality and variability in rat stroke experiments : a meta-analysis
- 2013
-
Ingår i: BMC Neuroscience. - London, United Kingdom : BioMed Central. - 1471-2202. ; 14:41
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundEven though more than 600 stroke treatments have been shown effective in preclinical studies, clinically proven treatment alternatives for cerebral infarction remain scarce. Amongst the reasons for the discrepancy may be methodological shortcomings, such as high mortality and outcome variability, in the preclinical studies. A common approach in animal stroke experiments is that A) focal cerebral ischemia is inflicted, B) some type of treatment is administered and C) the infarct sizes are assessed. However, within this paradigm, the researcher has to make numerous methodological decisions, including choosing rat strain and type of surgical procedure. Even though a few studies have attempted to address the questions experimentally, a lack of consensus regarding the optimal methodology remains.MethodsWe therefore meta-analyzed data from 502 control groups described in 346 articles to find out how rat strain, procedure for causing focal cerebral ischemia and the type of filament coating affected mortality and infarct size variability.ResultsThe Wistar strain and intraluminal filament procedure using a silicone coated filament was found optimal in lowering infarct size variability. The direct and endothelin methods rendered lower mortality rate, whereas the embolus method increased it compared to the filament method.ConclusionsThe current article provides means for researchers to adjust their middle cerebral artery occlusion (MCAo) protocols to minimize infarct size variability and mortality.
|
|
| 48. |
- Ström, Jakob O., 1983-, et al.
(författare)
-
Impact of methodology on estrogens' effects on cerebral ischemia in rats : an updated meta-analysis
- 2014
-
Ingår i: BMC Neuroscience. - London : BioMed Central (BMC). - 1471-2202. ; 15
-
Forskningsöversikt (refereegranskat)abstract
- Background: Although most animal stroke studies have demonstrated potent neuroprotective effects of estrogens, there are a number of articles reporting the opposite. In 2009, we made the case that this dichotomy was related to administered estrogen dose. Several other suggestions for the discordant results have also been propagated, including the age of the experimental animals and the length of hypoestrogenicity prior to estrogen administration. These two suggestions have gained much popularity, probably because of their kinship with the window of opportunity hypothesis, which is commonly used to explain the analogous dichotomy among human studies. We were therefore encouraged to perform an updated meta-analysis, and to improve it by including all relevant variables in a large multiple regression model, where the impact of confounders could be controlled for.Results: The multiple regression model revealed an indisputable impact of estrogen administration mode on the effects of estrogens in ischemic stroke. Subcutaneous slow-release pellets differed from the injection and silastic capsule treatments in terms of impact of estrogens on ischemic stroke, showing that the first mentioned were more prone to render estrogens damaging. Neither the use of elderly animals nor the adoption of longer wash-out periods influenced estrogens' effects on experimental ischemic stroke in rats.Conclusions: We conclude that the discordant results regarding estrogens' effects in rat models of ischemic stroke are a consequence of differences in estrogen administration modes. These results are not only of importance for the ongoing debate regarding menopausal hormone therapy, but also have an important bearing on experimental stroke methodology and the apparent translational roadblock for suggested stroke interventions.
|
|
| 49. |
- Trolle, Carl, et al.
(författare)
-
Boundary cap neural crest stem cells homotopically implanted to the injured dorsal root transitional zone give rise to different types of neurons and glia in adult rodents
- 2014
-
Ingår i: BMC Neuroscience. - : BioMed Central. - 1471-2202. ; 15, s. 60-
-
Tidskriftsartikel (refereegranskat)abstract
- The boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development. Later, these cells migrate to dorsal root ganglia and differentiate into subtypes of sensory neurons and glia. After birth when the DRTZ is established, sensory axons are no longer able to enter the spinal cord. Here we explored the fate of mouse bNCSCs implanted to the uninjured DRTZ after dorsal root avulsion for their potential to assist sensory axon regeneration. Grafted cells showed extensive survival and differentiation after transplantation to the avulsed DRTZ. Transplanted cells located outside the spinal cord organized elongated tubes of Sox2/GFAP expressing cells closely associated with regenerating sensory axons or appeared as small clusters on the surface of the spinal cord. Others, migrating into the host spinal cordas single cells, differentiated to spinal cord neurons with different neurotransmitter characteristics, extensive fiber organization, and in some cases surrounded by glutamatergic terminal-like profiles. These findings demonstrate that bNCSCs implanted at the site of dorsal root avulsion injury display remarkable differentiation plasticity inside the spinal cord and in the peripheral compartment where they organize tubes associated with regenerating sensory fibers. These properties offer a basis for exploring the ability of bNCSCs to assist regeneration of sensory axons into the spinal cord and replace lost neurons in the injured spinal cord.
|
|
| 50. |
- Westberg, Lars, 1973, et al.
(författare)
-
Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse brain.
- 2009
-
Ingår i: BMC neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 10:41
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gap junction proteins, connexins, are expressed in most endocrine and exocrine glands in the body and are at least in some glands crucial for the hormonal secretion. To what extent connexins are expressed in neurons releasing hormones or neuropeptides from or within the central nervous system is, however, unknown. Previous studies provide indirect evidence for gap junction coupling between subsets of neuropeptide-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Here we employ double labeling and retrograde tracing methods to investigate to what extent neuroendocrine and neuropeptide-containing neurons of the hypothalamus and brainstem express the neuronal gap junction protein connexin 36. RESULTS: Western blot analysis showed that connexin 36 is expressed in the PVN. In bacterial artificial chromosome transgenic mice, which specifically express the reporter gene Enhanced Green Fluorescent Protein (EGFP) under the control of the connexin 36 gene promoter, EGFP expression was detected in magnocellular (neuroendocrine) and in parvocellular neurons of the PVN. Although no EGFP/connexin36 expression was seen in neurons containing oxytocin or vasopressin, EGFP/connexin36 was found in subsets of PVN neurons containing corticotropin-releasing hormone (CRH), and in somatostatin neurons located along the third ventricle. Moreover, CRH neurons in brainstem areas, including the lateral parabrachial nucleus, also expressed EGFP/connexin 36. CONCLUSION: Our data indicate that connexin 36 is expressed in subsets of neuroendocrine and CRH neurons in specific nuclei of the hypothalamus and brainstem.
|
|
