Cerebrospinal fluid markers in Creutzfeldt-Jakob disease

<p>Abstract</p> <p>Background</p> <p>The objective was to assess the utility of total tau protein (tTau), the ratio of (tTau)/181 phosphorylated tau protein (P-Tau) and 14-3-3 protein, as diagnostic markers in cerebrospinal fluid (CSF) for Creutzfeldt-Jakob disease (CJD).</p> <p>Methods</p> <p>CSF samples received from Norwegian hospitals between August 2005 and August 2007 were retrospectively selected from consecutive patients with tTau values > 1200 ng/L (n = 38). The samples from patients clinically diagnosed with CJD (n = 12) were compared to those from patients with other degenerative neurological diseases: Alzheimer's/vascular dementia (AD/VaD, n = 21), other neurological diseases (OND, n = 5). Total Tau, P-Tau, and β-Amyloid (Aβ₄₂) were measured with commercial kits. Additionally, 14-3-3 protein was measured semi-quantitatively by immunoblot.</p> <p>Results</p> <p>The minimum cut-off limits for diagnosis of CJD were chosen from the test results. For tTau the lower limit was fixed at 3000 ng/L, for the tTau/P-Tau ratio it was 60, and for 14-3-3 protein it was 0.75 arbitrary units. For tTau and tTau/P-Tau ratio, all but three CJD patients had levels above the minimum, whereas almost all of the other patients were below. For the 14-3-3 protein, two CJD patients were below the minimum and five were above. Only one of the other patients was higher than the limit. The sensitivities, specificities and diagnostic efficiencies were: tTau 75%, 92%, and 87%; tTau/P-Tau 75%, 96%, and 89%; and 14-3-3 protein 80%, 96%, and 91%.</p> <p>Conclusion</p> <p>The results suggest that 14-3-3 protein may be the better marker for CJD, tTau/P-Tau ratio and tTau are also efficient markers, but showed slightly inferior diagnostic properties in this study, with tTau/P-Tau marginally better than tTau.</p

A Role for Glutamate Transporters in the Regulation of Insulin Secretion

In the brain, glutamate is an extracellular transmitter that mediates cell-to-cell communication. Prior to synaptic release it is pumped into vesicles by vesicular glutamate transporters (VGLUTs). To inactivate glutamate receptor responses after release, glutamate is taken up into glial cells or neurons by excitatory amino acid transporters (EAATs). In the pancreatic islets of Langerhans, glutamate is proposed to act as an intracellular messenger, regulating insulin secretion from beta-cells, but the mechanisms involved are unknown. By immunogold cytochemistry we show that insulin containing secretory granules express VGLUT3. Despite the fact that they have a VGLUT, the levels of glutamate in these granules are low, indicating the presence of a protein that can transport glutamate out of the granules. Surprisingly, in beta-cells the glutamate transporter EAAT2 is located, not in the plasma membrane as it is in brain cells, but exclusively in insulin-containing secretory granules, together with VGLUT3. In EAAT2 knock out mice, the content of glutamate in secretory granules is higher than in wild type mice. These data imply a glutamate cycle in which glutamate is carried into the granules by VGLUT3 and carried out by EAAT2. Perturbing this cycle by knocking down EAAT2 expression with a small interfering RNA, or by over-expressing EAAT2 or a VGLUT in insulin granules, significantly reduced the rate of granule exocytosis. Simulations of granule energetics suggest that VGLUT3 and EAAT2 may regulate the pH and membrane potential of the granules and thereby regulate insulin secretion. These data suggest that insulin secretion from beta-cells is modulated by the flux of glutamate through the secretory granules

Kommunene på Agder og opptrappingsplanen på rusfeltet : den sektoriserte stat møter kommunene

During the last 25 years there have been several efforts to strengthen the services to patients with mental health problems and substance use disorders. The new plan (opptrappingsplanen for rusfeltet) was launched in 2016 and will be completed in 2020. Again, as in previous efforts, it is the municipal health services that are going to do the job. This study examined the size of staff in these services in relation to population, and the proportion of employees in these services in relation to the total number of employees in the municipality. According to the results of this study, it is the smallest municipalities that have the highest number of employees working in the mental health and substance abuse services in relation to the population. However, the study also showed the largest municipalities have the highest percentage of employees in these services in relation to the total number of staff in the municipality. Furthermore, the study examined whether the services to patients with mental health problems and substance use disorders were mentioned in the municipality's financial plans and budgets on two variables i.e. management and sensitivity to governmental expectations as expressed in the plan. The study showed that the largest municipalities have the highest scores on these variables. The study concludes that the size of staff in relation to population does not give a realistic picture of how strongly the municipality prioritizes this field. The article proposes to use the staff percentage of employees in these services in relation to the total number of staff in this field as a better measure of the municipality priorities in this field. Keywords: mental health problems, substance use disorders, municipalities, health polic

LOC689986, a unique gene showing specific expression in restricted areas of the rodent neocortex

Background The neocortex is a highly specialised and complex brain structure, involved in numerous tasks, ranging from processing and interpretation of somatosensory information, to control of motor functions. The normal function linked to distinct neocortical areas might involve control of highly specific gene expression, and in order to identify such regionally enriched genes, we previously analysed the global gene expression in three different cortical regions (frontomedial, temporal and occipital cortex) from the adult rat brain. We identified distinct sets of differentially expressed genes. One of these genes, namely the hypothetical protein LOC689986 (LOC689986), was of particular interest, due to an almost exclusive expression in the temporal cortex. Results Detailed analysis of LOC689986 in the adult rat brain confirmed the expression in confined areas of parieto-temporal cortex, and revealed highly specific expression in layer 4 of the somatosensory cortex, with sharp borders towards the neighbouring motor cortex. In addition, LOC689986 was found to be translated in vivo, and was detected in the somatosensory cortex and in the Purkinje cells of the cerebellar cortex. The protein was present in neuronal dendrites and also in astrocyte cells. Finally, this unique gene is apparently specific for, and highly conserved in, the vertebrate lineage. Conclusions In this study, we have partially characterised the highly conserved LOC689986 gene, which is specific to the vertebrate linage. The gene displays a distinct pattern of expression in layer 4 of the somatosensory cortex, and areas of the parieto-temporal cortex in rodents

Mulihetsanalyse for Hokksund Sentrum Vest

Last ned gratis I dette notatet analyseres mulighetene for utbygging av en ny bydel sentralt i Hokksund. Først belyser vi overordnete planer og føringer for byutvikling, deretter drøftes de fysiske mulighetene og utfordringene. Til slutt undersøker vi betingelsene for handel og næring i tilknytning til prosjektet. Tilknyttet prosjekt Mulighetsanalyse for Hokksund Sentrum Ves

Regionale tyngdepunkt i Sør-Trøndelag

Rapporten inngår som en del av faktagrunnlaget til fylkeskommunens arbeid med Regional planstrategi i fylket. Rapporten presenterer et bredt tematisk og empirisk materiale over alle kommuner og bo- og arbeidsmarkedsregioner i Sør-Trøndelag, og peker også ut enkelte potensielle regionale tyngdepunkter og beskriver noen av deres egenskaper

Immunogold characteristics of VGLUT3-positive GABAergic nerve terminals suggest corelease of glutamate

There is compelling evidence that glutamate can act as a cotransmitter in the mammalian brain. Interestingly, the third vesicular glutamate transporter (VGLUT3) is primarily found in neurons that were anticipated to be nonglutamatergic. Whereas the function of VGLUT3 in acetylcholinergic and serotoninergic neurons has been elucidated, the role of VGLUT3 in neurons releasing gamma-aminobutyric acid (GABA) is not settled. We have previously shown that VGLUT3 is found together with the vesicular GABA transporter (VIAAT) on synaptic vesicle membranes in the hippocampus. Now we provide novel electron microscopic data from the rat hippocampus suggesting that glutamate is enriched in inhibitory nerve terminals containing VGLUT3 compared to those lacking VGLUT3. The opposite was found for GABA; VGLUT3-positive inhibitory terminals contained lower density of GABA labeling compared to VGLUT3-negative inhibitory terminals. In addition, semiquantitative confocal immunofluorescence showed that N-methyl-D-aspartate (NMDA)-receptor labeling was present more frequently in VGLUT3-positive/VIAAT-positive synapses versus in VGLUT3-negative/VIAAT-positive synapses. Electron microscopic immunogold data further suggest that NMDA receptors are enriched in VGLUT3 containing inhibitory terminals. Our data reveal new chemical characteristics of a subset of GABAergic interneurons in the hippocampus. The analyses suggest that glutamate is coreleased with GABA from hippocampal basket cell-synapses to act on NMDA receptors. J. Comp. Neurol. 523:2698–2713, 2015. © 2015 Wiley Periodicals, Inc

A distinct set of synaptic-like microvesicles in atroglial cells contain VGLUT3

There is increasing evidence for vesicular release of glutamate from astrocytes. We have previously demonstrated existence of VGLUT1 on astrocytic synaptic-like microvesicles (SMLVs) in several brain regions indicating a role in astroglial glutamate release. As VGLUT3 is prominently expressed in non-neuronal cells, this prompted us to investigate whether VGLUT3 is also involved in astroglial release of glutamate. Confocal microscopic investigations revealed that astrocytes in the hippocampus and the frontal cortex, as well as Bergmann glia in the cerebellum were labeled for VGLUT3. Immunogold cytochemistry showed that VGLUT3 gold particles were located over SMLVs in perisynaptic astrocytic and Bergmann glial processes. The specificity of the VGLUT3 immunoreactivity was demonstrated by abolished VGLUT3 labeling in astroglia in VGLUT3 knock-out mice. Double immunogold labeling showed that astrocytic processes contained labeling for VGLUT3 and VGLUT1, but the antibodies labeled separate subpopulations of vesicles in the processes. The ratio of gold particle densities between glial processes and nerve terminals were higher for VGLUT3 than for VGLUT1, suggesting that VGLUT3 is particularly abundant in astrocytic processes. Thus, our data show that VGLUT3 localizes to a distinct set of SMLVs in perisynaptic astroglial processes and suggest that VGLUT3 is important for glutamate release from astrocytes. © 2012 Wiley Periodicals, Inc