| 1. |
- Albrecht, Daniel S., et al.
(författare)
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Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation
- 2019
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 75, s. 72-83
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Tidskriftsartikel (refereegranskat)abstract
- Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C-11]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C-11]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C-11]PBR28 PET. 11 FM patients and 11 HC were scanned using [C-11]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (V-T) were computed from the [C-11]PBR28 data. [C-11]-L-deprenyl-D2 was quantified using lambda k(3). PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [C-11]PBR28 ITT and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [C-11]-L-deprenyl-Ds signal, including those demonstrating elevated [C-11] PBR28 signal in patients (p's >= 0.53, uncorrected). The elevations in [C-11]PBR28 V-T and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [C-11] PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [C-11]PBR28 signal were not also accompanied by increased [C-11]-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [C-11]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.
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| 2. |
- Bermejo Gómez, Antonio, et al.
(författare)
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Efficient DBU accelerated synthesis of F-18-labelled trifluoroacetamides
- 2016
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 52:97, s. 13963-13966
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Tidskriftsartikel (refereegranskat)abstract
- Nucleophilic F-18-fluorination of bromodifluoromethyl derivatives was performed using [F-18] Bu4NF in the presence of DBU(1,8-diazabicyclo[5.4.0]undec-7-ene). This novel procedure provided a diverse set of [F-18] trifluoroacetamides in good to excellent radiochemical conversions. A mechanism where DBU acts as organomediator in this transformation is proposed.
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| 3. |
- Braniste, Viorica, et al.
(författare)
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The gut microbiota influences blood-brain barrier permeability in mice
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 6:263, s. 263ra158-
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Tidskriftsartikel (refereegranskat)abstract
- Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota-BBB communication is initiated during gestation and propagated throughout life.
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| 4. |
- Carlson, Karin, et al.
(författare)
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Language policy for a bilingual faculty
- 2005
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Ingår i: Bi- and multilingual universities, Helsinki, Finland, Sept 1-3, 2005.
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Konferensbidrag (refereegranskat)abstract
- The Faculty of Science and Technology of Uppsala University is for all practical purposes a bilingual institution, using both Swedish and English in education and research. Extensive use of English in teaching, and also in intrauniversity communication, permits recruitment of nonSwedishspeaking students, researchers and professors, and also prepares our students forinternational careers. However, the introduction of English has been somewhat haphazard, not taking into account possible negative effects on communication in Swedish, nor on students'learning.In order to improve students' and professors' language skills, and achieve a good balance between Swedish and English, the faculty board appointed a language committee in 2003 whose task was to propose a language policy for the faculty. A first part, stating as a main goal that all communication from and within the faculty should have the highest quality possible, has been adopted by the board. A second part including language planning with respect to status, corpus, and acquisition for both Swedish and English to accomplish this goal was sent to the board of the faculty in May, 2005. Implementation of this policy will affect all faculty activities, especially education. Suggestedannual reports on language status will raise our present minimal knowledge about possible domain losses and allow for relevant countermeasures.
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| 5. |
- Cervenka, Simon, et al.
(författare)
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Age-related diurnal effect on D-2 receptor binding : a preliminary PET study
- 2008
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Ingår i: International Journal of Neuropsychopharmacology. - : OXFORD UNIV PRESS. - 1461-1457 .- 1469-5111. ; 11:5, s. 671-678
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Tidskriftsartikel (refereegranskat)abstract
- Animal research has shown a diurnal variation in dopamine neurotransmission, with a reduced release at night. Variations in biomarkers for the dopamine system over the day have, however, not been investigated in human subjects. In this preliminary PET study, we used the radioligands [C-11]raclopride and [C-11]FLB457 to determine dopamine D-2-receptor binding in 16 human subjects in the morning and evening on the same day. The average difference between morning and evening examinations did not indicate a diurnal effect on D-2 receptor availability. However, when age was taken into account in the analysis, a pattern emerged where individuals in the lower age range showed reduced evening binding while in older subjects binding potential increased. The product-moment correlation between morning-evening change and age was statistically significant in insula, medial frontal cortex and rostral anterior cingulate. The findings, if replicated, have direct relevance for applied PET studies and could also prove relevant with regard to age effects on dopamine-related behaviour such as arousal and cognitive performance.
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| 6. |
- Cervenka, Simon, et al.
(författare)
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Association between striatal and extrastriatal dopamine D2-receptor binding and social desirability
- 2010
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 50:1, s. 323-328
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Tidskriftsartikel (refereegranskat)abstract
- Research on the biological underpinnings of personality can provide leads to the pathophysiology of psychiatric disorders. In particular, interpersonal aspects of behavior are a common problem during the course of psychiatric illness. Animal research has demonstrated a role for the dopamine system in social behaviour, and recent molecular imaging studies have shown a negative correlation between dopamine D2-receptor binding in the striatum and social desirability. The emotional and cognitive aspects of social behavior suggest involvement of brain regions outside of the striatum, such as limbic structures. The aim of the present study was to explore associations between the personality trait social desirability and dopamine D2-receptor binding in both striatal and extrastriatal brain regions. We examined 16 control subjects with Positron Emission Tomography and the radioligands [C-11]raclopride and [C-11]FLB 457, in relation to social desirability in the inventory Swedish universities Scales of Personality. [C-11]raclopride D2-receptor binding in the striatum showed negative correlations to social desirability scores, corroborating previous findings. Furthermore, a correlation of a higher statistical significance was demonstrated for [C-11]FLB 457 binding in the hippocampal-amygdala complex. A separate analysis of social desirability items in relation to a model of interpersonal behaviour revealed that the associations were driven by items reflecting high submissiveness and high affiliation. Taken together with previous evidence on D2-receptor binding and social behaviour, a role for dopaminergic neurotransmission in regulating displays of dominance vs. submissive behaviour is proposed. (C) 2009 Elsevier B.V. All rights reserved.
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| 7. |
- Cervenka, Simon, et al.
(författare)
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Associations between dopamine D2-receptor binding and cognitive performance indicate functional compartmentalization of the human striatum
- 2008
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 40:3, s. 1287-1295
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Tidskriftsartikel (refereegranskat)abstract
- Based on pharmacological, neuroanatomical, and lesion studies in animals, a functional compartmentalization of the striatal complex has been proposed. However, this has not been convincingly demonstrated in human subjects. Most functions ascribed to the striatum have been linked to its dense dopaminergic innervation, from motor control to higher-order brain functions ( e. g., cognition), making the dopamine system a suitable probe for striatal function. Limbic striatum, a region involved in reward processing, has recently been implicated also in episodic memory function. Here we examined striatal dopamine D2-receptor binding in 16 healthy subjects using PET and the radioligand [C-11] raclopride, in relation to cognitive performance. Receptor availability in limbic striatum was related to performance in tests of episodic memory, but not to tests of verbal fluency and general knowledge. By contrast, D2 binding in associative and sensorimotor striatum was less strongly related to episodic memory, but showed associations to the non-episodic tasks. These findings provide biochemical evidence for a functional compartmentalization of human striatum, and serve as a starting point for a more detailed investigation of striatal biomarkers in the normal brain as well as in neurodegenerative disorders. (c) 2008 Elsevier Inc. All rights reserved.
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| 8. |
- Cervenka, Simon, et al.
(författare)
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PET Studies of D2-Receptor Binding in Striatal and Extrastriatal Brain Regions : Biochemical Support In Vivo for Separate Dopaminergic Systems in Humans
- 2010
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Ingår i: Synapse. - : Wiley. - 0887-4476 .- 1098-2396. ; 64:6, s. 478-485
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Tidskriftsartikel (refereegranskat)abstract
- Most molecular imaging studies of the dopamine (DA) system performed to date have focused on the striatum, a region receiving dense dopaminergic innervation. In clinical research on the DA D2-receptor, striatal binding has often been regarded as an index of global DA function, based on the underlying assumption of common regulatory mechanisms for receptor expression across brain regions. Recent data has challenged this view, suggesting differences in genetic regulation between striatal and extrastriatal brain regions. The relationship between binding levels in brain regions has, however, not been directly examined in the same sample. In this study, we searched for interregional correlations between DA D2-receptor availability as determined with Positron Emission Tomography in 16 control subjects. The radioligands [C-11]raclopride and [C-11]FLB 457 were used for measurements of D2-receptor binding in striatal and extrastriatal regions, respectively. No correlation was observed between D2-receptor availability in striatum and any of the extrastriatal regions, as assessed using both region of interest- and voxel-based analyses. Instead, the pattern of correlations was consistent with the model of separate dopaminergic systems as has been originally observed in rodents. These preliminary results encourage approaches searching for individual patterns of receptor binding across the whole brain volume in clinical studies on the dopamine system.
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| 9. |
- Cervenka, Simon, et al.
(författare)
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Support for dopaminergic hypoactivity in restless legs syndrome : a PET study on D2-receptor binding
- 2006
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Ingår i: Brain. - Karolinska Univ Hosp Solna, Dept Clin Neurosci, Psychol Sect, Karolinska Inst, SE-17176 Stockholm, Sweden. Karolinska Univ Hosp Huddinge, Div Clin Pharmacol, Dept Lab Med, Stockholm, Sweden. Karolinska Univ Hosp Huddinge, Dept Neurol, Stockholm, Sweden. GlaxoSmithKline Inc, Translat Med & Genet, Cambridge, England. Univ Manchester, Wolfson Mol Imaging Ctr, Manchester, Lancs, England. GlaxoSmithKline Inc, Neurol Discovery Med, Harlow, Essex, England. : OXFORD UNIV PRESS. - 0006-8950 .- 1460-2156. ; 129, s. 2017-2028
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Tidskriftsartikel (refereegranskat)abstract
- Clinical observations support a central role of the dopamine system in restless legs syndrome (RLS) but previous imaging studies of striatal dopamine D2-receptors have yielded inconclusive results. Extrastriatal dopaminergic function has hitherto not been investigated. Sixteen RLS patients naive to dopaminergic drugs and sixteen matched control subjects were examined with PET. [C-11]Raclopride and [C-11]FLB 457 were used to estimate D2-receptor availability in striatum and extrastriatal regions, respectively. Examinations were performed both in the morning (starting between 10:00 and 12:00 h) and evening (starting at 18:00 h). Measures were taken to monitor and control for head movement during data acquisition. In the striatum, patients had significantly higher [C-11]raclopride binding potential (BP) values than controls. In extrastriatal regions, [C-11]FLB 457 BP was higher in patients than controls, and in the regional analysis the difference was statistically significant in subregions of thalamus and the anterior cingulate cortex. The diurnal variability in BP with [C-11]FLB 457 and [C-11]raclopride was within the previously reported test-retest reproducibility for both radioligands. The study supports involvement of the dopamine system in both striatal and extrastriatal brain regions in the pathophysiology of RLS. The brain regions where differences in D2-receptor binding were shown are implicated in the regulation of affective and motivational aspects of sensory processing, suggesting a possible pathway for sensory symptoms in RLS. Increased D2-receptor availability in RLS may correspond to higher receptor densities or lower levels of endogenous dopamine. Both interpretations are consistent with the hypothesis of hypoactive dopaminergic neurotransmission in RLS, as increased receptor levels can be owing to receptor upregulation in response to low levels of endogenous dopamine. The results do not support variations in dopamine D2-receptor availability as a correlate to the diurnal rhythm of RLS symptoms.
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| 10. |
- Chiotis, Konstantinos, et al.
(författare)
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Dual tracer tau PET imaging reveals different molecular targets for C-11-THK5351 and C-11-PBB3 in the Alzheimer brain
- 2018
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 45:9, s. 1605-1617
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Tidskriftsartikel (refereegranskat)abstract
- Several tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers (C-11-THK5351 and C-11-PBB3) in a head-to-head, in vivo, multimodal design. Nine patients with a diagnosis of mild cognitive impairment or probable Alzheimer's disease and cerebrospinal fluid biomarker evidence supportive of the presence of Alzheimer's disease brain pathology were recruited after thorough clinical assessment. All patients underwent imaging with the tau-specific PET tracers C-11-THK5351 and C-11-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer C-11-AZD2184, a T1-MRI sequence, and neuropsychological assessment. The load and regional distribution of binding differed between C-11-THK5351 and C-11-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of C-11-PBB3, but not that of C-11-THK5351, in the temporal lobe resembled that of C-11-AZD2184, with strong correlations detected between C-11-PBB3 and C-11-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with C-11-THK5351 than with C-11-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with C-11-THK5351 than with C-11-PBB3 binding. This research suggests different molecular targets for these tracers; while C-11-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of C-11-THK5351 fitted the expected distribution of tau pathology in Alzheimer's disease better and was more closely related to downstream disease markers.
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