| 1. |
- Broms, Jonas, et al.
(författare)
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Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates.
- 2015
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 523:3, s. 359-380
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Tidskriftsartikel (refereegranskat)abstract
- The habenula is a phylogenetically conserved brain structure in the epithalamus. It is a major node in the information flow between fronto-limbic brain regions and monoaminergic brainstem nuclei, thus anatomically and functionally ideally positioned to regulate emotional, motivational and cognitive behaviors. Consequently, the habenula may be critically important in the pathophysiology of psychiatric disorders such as addiction and depression. Here we investigated the expression pattern of GPR151, a G coupled-protein receptor (GPCR), whose mRNA has been identified as highly and specifically enriched in habenular neurons by in situ hybridization and Translating Ribosome Affinity Purification (TRAP). In the present immunohistochemical study we demonstrate a pronounced and highly specific expression of the GPR151 protein in the medial and lateral habenula of rodent brain. Specific expression was also seen in efferent habenular fibers projecting to the interpeduncular nucleus, the rostromedial tegmental area, the rhabdoid nucleus, the mesencephalic raphe nuclei and the dorsal tegmental nucleus. Using confocal microscopy and quantitative colocalization analysis we found that GPR151 expressing axons and terminals overlap with cholinergic, substance P-ergic and glutamatergic markers. Virtually identical expression pattern was observed in rat, mouse and zebrafish brains. Our data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development. J. Comp. Neurol., 2014. © 2014 Wiley Periodicals, Inc.
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| 2. |
- Broms, Jonas, et al.
(författare)
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Monosynaptic retrograde tracing of neurons expressing the G-protein coupled receptor Gpr151 in the mouse brain
- 2017
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 525:15, s. 3227-3250
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Tidskriftsartikel (refereegranskat)abstract
- GPR151 is a G-protein coupled receptor for which the endogenous ligand remains unknown. In the nervous system of vertebrates, its expression is enriched in specific diencephalic structures, where the highest levels are observed in the habenular area. The habenula has been implicated in a range of different functions including behavioral flexibility, decision making, inhibitory control, and pain processing, which makes it a promising target for treating psychiatric and neurological disease. This study aimed to further characterize neurons expressing the Gpr151 gene, by tracing the afferent connectivity of this diencephalic cell population. Using pseudotyped rabies virus in a transgenic Gpr151-Cre mouse line, monosynaptic afferents of habenular and thalamic Gpr151-expressing neuronal populations could be visualized. The habenular and thalamic Gpr151 systems displayed both shared and distinct connectivity patterns. The habenular neurons primarily received input from basal forebrain structures, the bed nucleus of stria terminalis, the lateral preoptic area, the entopeduncular nucleus, and the lateral hypothalamic area. The Gpr151-expressing neurons in the paraventricular nucleus of the thalamus was primarily contacted by medial hypothalamic areas as well as the zona incerta and projected to specific forebrain areas such as the prelimbic cortex and the accumbens nucleus. Gpr151 mRNA was also detected at low levels in the lateral posterior thalamic nucleus which received input from areas associated with visual processing, including the superior colliculus, zona incerta, and the visual and retrosplenial cortices. Knowledge about the connectivity of Gpr151-expressing neurons will facilitate the interpretation of future functional studies of this receptor.
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| 3. |
- Broms, Loove, 1977-
(creator_code:cre_t)
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Beyond Efficiency
- 2020
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Konstnärligt arbete (refereegranskat)abstract
- Part of exhibition Human Nature at the Museum of Ethnography, Stockholm 26 September 2020 - 6 November 2022
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| 4. |
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| 6. |
- Jester-Broms, Jonas
(författare)
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Characterization of habenular neurocircuitry. A potential novel target for treating depression.
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the last decade, there has been an explosion of interest within the psychiatric research community in a small diencephalic brain region called the habenula. It has been uncovered as a key regulator of monoaminergic transmission, playing a fundamental role in decision making, behavioral flexibility, inhibitory control, sleep, pain and analgesia. Perturbation of the habenular neurocircutry in animals produce effects that mimic rewards and punishments, animals actively seek habenula inactivation while avoiding activation. From a psychiatric viewpoint, the habenula is a promising target for diseases like depression, drug dependence and ADHD. Given that the morphology and connectivity of the habenula is highly conserved throughout the vertebrate subphylum, animal research is both valid and necessary to map the circuitry and neuronal populations that constitute the habenular complex. Due to the small size and position of the habenula, techniques for modulating this brain area in humans are both invasive, difficult and risky. To overcome this issue, we have characterized an orphan G protein-coupled receptor (Gpr151) that may serve as a future non-invasive target for habenula modulation. We demonstrate that it is highly enriched in the habenular circuitry, with a pattern that is evolutionary conserved. Using monosynaptic pseudorabies and adenoassociated viral tracing techniques we have dissected the connectivity of the habenular neurons expressing the orphan G-protein coupled receptor Gpr151. We have also performed initial screening experiments with the aim of identifying ligands to the receptor. Our results indicate that Gpr151 can possibly modulate a brain network providing a link between the basal forebrain and neuromodulatory brain stem targets, a circuitry with a involved in a multitude of functions with importance for psychiatric disease. Moreover, we continued the characterization of the inhibitory interneurons in the habenula, a neuronal population which has received very little attention previously. The existence of various types of intrinsic neurons within the habenular nucleus adds to the already very complex picture of this intriguing structure. Psychiatry is in dire need of new effective treatments, and the habenula and Gpr151 might provide possible novel targets for psychopharmacological research and future drug development.
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| 7. |
- Ossenkoppele, Rik, et al.
(författare)
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Assessment of Demographic, Genetic, and Imaging Variables Associated with Brain Resilience and Cognitive Resilience to Pathological Tau in Patients with Alzheimer Disease
- 2020
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:5, s. 632-642
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience). Objective: To examine the demographic (age, sex, and educational level), genetic (APOE-ϵ4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors associated with interindividual differences in brain and cognitive resilience to tau positron emission tomography (PET) load and to changes in global cognition over time. Design, Setting, an Participants: In this cross-sectional, longitudinal study, tau PET was performed from June 1, 2014, to November 30, 2017, and global cognition monitored for a mean [SD] interval of 2.0 [1.8] years at 3 dementia centers in South Korea, Sweden, and the United States. The study included amyloid-β-positive participants with mild cognitive impairment or AD dementia. Data analysis was performed from October 26, 2018, to December 11, 2019. Exposures: Standard dementia screening, cognitive testing, brain magnetic resonance imaging, amyloid-β PET and cerebrospinal fluid analysis, and flortaucipir (tau) labeled with fluor-18 (18F) PET. Main Outcomes and Measures: Separate linear regression models were performed between whole cortex [18F]flortaucipir uptake and cortical thickness, and standardized residuals were used to obtain a measure of brain resilience. The same procedure was performed for whole cortex [18F]flortaucipir uptake vs Mini-Mental State Examination (MMSE) as a measure of cognitive resilience. Bivariate and multivariable linear regression models were conducted with age, sex, educational level, APOE-ϵ4 status, white matter hyperintensity volumes, and cortical thickness as independent variables and brain and cognitive resilience measures as dependent variables. Linear mixed models were performed to examine whether changes in MMSE scores over time differed as a function of a combined brain and cognitive resilience variable. Results: A total of 260 participants (145 [55.8%] female; mean [SD] age, 69.2 [9.5] years; mean [SD] MMSE score, 21.9 [5.5]) were included in the study. In multivariable models, women (standardized β =-0.15, P =.02) and young patients (standardized β =-0.20, P =.006) had greater brain resilience to pathological tau. Higher educational level (standardized β = 0.23, P <.001) and global cortical thickness (standardized β = 0.23, P <.001) were associated with greater cognitive resilience to pathological tau. Linear mixed models indicated a significant interaction of brain resilience × cognitive resilience × time on MMSE (β [SE] =-0.235 [0.111], P =.03), with steepest slopes for individuals with both low brain and cognitive resilience. Conclusions and Relevance: Results of this study suggest that women and young patients with AD have relative preservation of brain structure when exposed to neocortical pathological tau. Interindividual differences in resilience to pathological tau may be important to disease progression because participants with both low brain and cognitive resilience had the most rapid cognitive decline over time.
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| 8. |
- Wangel, Josefin, et al.
(författare)
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Epilogue
- 2021
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Ingår i: Beyond efficiency. - Baunach : AADR. - 9783887786113 ; , s. 199-203
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
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