| 1. |
- Vicari, Marco, et al.
(författare)
-
Spatial multimodal analysis of transcriptomes and metabolomes in tissues
- 2024
-
Ingår i: Nature Biotechnology. - : Nature Research. - 1087-0156 .- 1546-1696. ; 42:7, s. 1046-1050
-
Tidskriftsartikel (refereegranskat)abstract
- We present a spatial omics approach that combines histology, mass spectrometry imaging and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions. The workflow is compatible with commercially available Visium glass slides. We demonstrate the potential of our method using mouse and human brain samples in the context of dopamine and Parkinson’s disease.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Helson, Pascal, et al.
(författare)
-
Cortex-wide topography of 1/f-exponent in Parkinson's disease
- 2023
-
Ingår i: npj Parkinson's Disease. - : Springer Nature. - 2373-8057. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is a progressive and debilitating brain disorder. Besides the characteristic movement-related symptoms, the disease also causes decline in sensory and cognitive processing. The extent of symptoms and brain-wide projections of neuromodulators such as dopamine suggest that many brain regions are simultaneously affected in PD. To characterise brain-wide disease-related changes in neuronal function, we analysed resting state magnetoencephalogram (MEG) from two groups: PD patients and healthy controls. Besides standard spectral analysis, we quantified the aperiodic components (& kappa;, & lambda;) of the neural activity by fitting a power law & kappa;/f(& lambda;) - f is the frequency, & kappa; and & lambda; are the fitting parameters-to the MEG power spectrum and studied its relationship with age and Unified Parkinson's Disease Rating Scale (UPDRS). Consistent with previous results, the most significant spectral changes were observed in the high theta/low-alpha band (7-10 Hz) in all brain regions. Furthermore, analysis of the aperiodic part of the spectrum showed that in all but frontal regions & lambda; was significantly larger in PD patients than in control subjects. Our results indicate that PD is associated with significant changes in aperiodic activity across the whole neocortex. Surprisingly, even early sensory areas showed a significantly larger & lambda; in patients than in healthy controls. Moreover, & lambda; was not affected by the Levodopa medication. Finally, & lambda; was positively correlated with patient age but not with UPDRS-III. Because & lambda; is closely associated with excitation-inhibition balance, our results propose new hypotheses about neural correlates of PD in cortical networks.
|
|
| 5. |
|
|
| 6. |
- Kotliar, Ilana B., et al.
(författare)
-
Multiplexed mapping of the interactome of GPCRs with receptor activity-modifying proteins
- 2024
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:31, s. 9959-
-
Tidskriftsartikel (refereegranskat)abstract
- Receptor activity-modifying proteins (RAMPs) form complexes with G protein-coupled receptors (GPCRs) and may regulate their cellular trafficking and pharmacology. RAMP interactions have been identified for about 50 GPCRs, but only a few GPCR-RAMP complexes have been studied in detail. To elucidate a comprehensive GPCR-RAMP interactome, we created a library of 215 dual epitope-tagged (DuET) GPCRs representing all GPCR subfamilies and coexpressed each GPCR with each of the three RAMPs. Screening the GPCR-RAMP pairs with customized multiplexed suspension bead array (SBA) immunoassays, we identified 122 GPCRs that showed strong evidence for interaction with at least one RAMP. We screened for interactions in three cell lines and found 23 endogenously expressed GPCRs that formed complexes with RAMPs. Mapping the GPCR-RAMP interactome expands the current system-wide functional characterization of RAMP-interacting GPCRs to inform the design of selective therapeutics targeting GPCR-RAMP complexes.
|
|
| 7. |
- Liebmann, Thomas, et al.
(författare)
-
A Noncanonical Postsynaptic Transport Route for a GPCR Belonging to the Serotonin Receptor Family
- 2012
-
Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:50, s. 17998-18008
-
Tidskriftsartikel (refereegranskat)abstract
- Postsynaptic receptor trafficking plays an essential role in tuning neurotransmission and signal plasticity and has emerged as a potential therapeutic target in neuropsychiatric disease. Using a novel application of fluorescence recovery after photobleaching in rat hippocampal neurons, we examined transport from the soma to dendrites of seven G-protein-coupled receptors (GPCRs) implicated in mood disorders. Most GPCRs were delivered to dendrites via lateral diffusion, but one GPCR, the serotonin 1B receptor (5-HT1B), was delivered to the dendrites in secretory vesicles. Within the dendrites, 5-HT1B were stored in a reservoir of accessible vesicles that were recruited to preferential sites in plasma membrane, as observed with superecliptic pHluorin labeling. After membrane recruitment, 5-HT1B transport via lateral diffusion and temporal confinement to inhibitory and excitatory synapses was monitored by single particle tracking. These results suggest an alternative mechanism for control of neuronal activity via a GPCR that has been implicated in mood regulation.
|
|
| 8. |
- Remnestål, Julia, et al.
(författare)
-
CSF profiling of the human brain enriched proteome reveals associations of neuromodulin and neurogranin to Alzheimer's disease
- 2016
-
Ingår i: PROTEOMICS - Clinical Applications. - : Wiley-VCH Verlagsgesellschaft. - 1862-8346 .- 1862-8354. ; 10:12, s. 1242-1253
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study is part of a larger effort aiming to expand the knowledge of brain-enriched proteins in human cerebrospinal fluid (CSF) and to provide novel insight into the relation between such proteins and different neurodegenerative diseases. Experimental design: Here 280 brain-enriched proteins in CSF from patients with Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are profiled. In total, 441 human samples of ventricular CSF collected post mortem and lumbar CSF collected ante mortem are analyzed using 376 antibodies in a suspension bead array setup, utilizing a direct labelling approach. Results: Among several proteins displaying differentiated profiles between sample groups, we focus here on two synaptic proteins, neuromodulin (GAP43) and neurogranin (NRGN). They are both found at elevated levels in CSF from AD patients in two independent cohorts, providing disease-associated profiles in addition to verifying and strengthening previously observed patterns. Increased levels are also observed for patients for whom the AD diagnosis was not established at the time of sampling. Conclusions and clinical relevance: These findings indicate that analyzing the brain-enriched proteins in CSF is of particular interest to increase the understanding of the CSF proteome and its relation to neurodegenerative disorders. In addition, this study lends support to the notion that measurements of these synaptic proteins could potentially be of great relevance in future diagnostic tests for AD.
|
|
