| 1. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 3. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Chaney, Aisling M., et al.
(author)
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Prodromal neuroinflammatory, cholinergic and metabolite dysfunction detected by PET and MRS in the TgF344-AD transgenic rat model of AD : a collaborative multi-modal study
- 2021
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In: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:14, s. 6644-6667
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Journal article (peer-reviewed)abstract
- Mouse models of Alzheimer's disease (AD) are valuable but do not fully recapitulate human AD pathology, such as spontaneous Tau fibril accumulation and neuronal loss, necessitating the development of new AD models. The transgenic (TG) TgF344-AD rat has been reported to develop age-dependent AD features including neuronal loss and neurofibrillary tangles, despite only expressing APP and PSEN1 mutations, suggesting an improved modelling of AD hallmarks. Alterations in neuronal networks as well as learning performance and cognition tasks have been reported in this model, but none have combined a longitudinal, multimodal approach across multiple centres, which mimics the approaches commonly taken in clinical studies. We therefore aimed to further characterise the progression of AD-like pathology and cognition in the TgF344-AD rat from young-adults (6 months (m)) to mid- (12 m) and advanced-stage (18 m, 25 m) of the disease.Methods: TgF344-AD rats and wild-type (WT) littermates were imaged at 6 m, 12 m and 18 m with [18F]DPA-714 (TSPO, neuroinflammation), [18F]Florbetaben (Aβ) and [18F]ASEM (α7-nicotinic acetylcholine receptor) and with magnetic resonance spectroscopy (MRS) and with (S)-[18F]THK5117 (Tau) at 15 and 25 m. Behaviour tests were also performed at 6 m, 12 m and 18 m. Immunohistochemistry (CD11b, GFAP, Aβ, NeuN, NeuroChrom) and Tau (S)-[18F]THK5117 autoradiography, immunohistochemistry and Western blot were also performed.Results: [18F]DPA-714 positron emission tomography (PET) showed an increase in neuroinflammation in TG vs wildtype animals from 12 m in the hippocampus (+11%), and at the advanced-stage AD in the hippocampus (+12%), the thalamus (+11%) and frontal cortex (+14%). This finding coincided with strong increases in brain microgliosis (CD11b) and astrogliosis (GFAP) at these time-points as assessed by immunohistochemistry. In vivo [18F]ASEM PET revealed an age-dependent increase uptake in the striatum and pallidum/nucleus basalis of Meynert in WT only, similar to that observed with this tracer in humans, resulting in TG being significantly lower than WT by 18 m. In vivo [18F]Florbetaben PET scanning detected Aβ accumulation at 18 m, and (S)-[18F]THK5117 PET revealed subsequent Tau accumulation at 25m in hippocampal and cortical regions. Aβ plaques were low but detectable by immunohistochemistry from 6 m, increasing further at 12 and 18 m with Tau-positive neurons adjacent to Aβ plaques at 18 m. NeuroChrom (a pan neuronal marker) immunohistochemistry revealed a loss of neuronal staining at the Aβ plaques locations, while NeuN labelling revealed an age-dependent decrease in hippocampal neuron number in both genotypes. Behavioural assessment using the novel object recognition task revealed that both WT & TgF344-AD animals discriminated the novel from familiar object at 3 m and 6 m of age. However, low levels of exploration observed in both genotypes at later time-points resulted in neither genotype successfully completing the task. Deficits in social interaction were only observed at 3 m in the TgF344-AD animals. By in vivo MRS, we showed a decrease in neuronal marker N-acetyl-aspartate in the hippocampus at 18 m (-18% vs age-matched WT, and -31% vs 6 m TG) and increased Taurine in the cortex of TG (+35% vs age-matched WT, and +55% vs 6 m TG).Conclusions: This multi-centre multi-modal study demonstrates, for the first time, alterations in brain metabolites, cholinergic receptors and neuroinflammation in vivo in this model, validated by robust ex vivo approaches. Our data confirm that, unlike mouse models, the TgF344-AD express Tau pathology that can be detected via PET, albeit later than by ex vivo techniques, and is a useful model to assess and longitudinally monitor early neurotransmission dysfunction and neuroinflammation in AD.
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| 5. |
- Busson, P., et al.
(author)
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Preparation of mesogen-functionalized dendrimers for second-order nonlinear optics
- 2002
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In: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 35:5, s. 1663-1671
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Journal article (peer-reviewed)abstract
- Liquid crystalline dendrimers with peripheral mesogen-containing units have been prepared. Multistep synthesis with several selective reactions was used in the preparation of the mesogen-containing molecules, 4-[10-(hydroxycarbonyl)decyloxy]phenyl 4-[4'-(2-(R)-octyloxy)-3'-nitrophenyl]benzo ate and 4-[10-(hydroxycarbonyl)decyloxy]biphenyl 4-[4'-(2-(R)-octyloxy)-3'-nitrophenyl]benzoate. Both molecules possessed an electron-accepting nitro group placed perpendicular to the long axis of the molecules in order to enhance the nonlinear optical activity. A second generation hydroxyl functional aliphatic dendrimer based on the dihydroxy acid, 2,2-bis(hydroxymethyl)propionic acid, was used as dendritic scaffold and was subsequently functionalized with the aforementioned groups. The purity and structure of the two liquid crystalline dendrimers were determined by H-1 NMR spectroscopy, size exclusion chromatography, and elemental analysis. The synthesis of both the mesogen-containing units and the liquid crystalline dendrimers is described in detail. Investigation of the liquid crystalline properties of the materials by differential scanning calorimetry and optical microscopy showed that they exhibited different mesophases, including the chiral smectic C phase. Ferroelectric switching was observed in this tilted phase, and electrooptical properties, including tilt angle and spontaneous polarization measurements, were investigated. Finally, the nonlinear optical properties of one of the materials were preliminary characterized.
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| 6. |
- Dalstein, Laetitia, et al.
(author)
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Nonlinear optical response of a gold surface in the visible range : A study by two-color sum-frequency generation spectroscopy. I. Experimental determination
- 2018
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In: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 148:13
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Journal article (peer-reviewed)abstract
- We experimentally determine the effective nonlinear second-order susceptibility of gold over the visible spectral range. To reach that goal, we probe by vibrational two-color sum-frequency generation spectroscopy the methyl stretching region of a dodecanethiol self-assembled monolayer adsorbed on a gold film. The sum-frequency generation spectra show a remarkable shape reversal when the visible probe wavelength is tuned from 435 to 705 nm. After correcting from Fresnel effects, the methyl stretching vibrations serve as an internal reference, allowing to extract the dispersion of the absolute phase and relative amplitude of the effective nonlinear optical response of gold in the visible range.
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| 7. |
- Nielsen, Morten A., et al.
(author)
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Increased Galectin-9 Levels Correlate with Disease Activity in Patients with DMARD-Naïve Rheumatoid Arthritis and Modulate the Secretion of MCP-1 and IL-6 from Synovial Fibroblasts
- 2023
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In: Cells. - : MDPI AG. - 2073-4409. ; 12:2
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Journal article (peer-reviewed)abstract
- Background: Fibroblast-like synoviocytes (FLSs) are essential mediators in the expansive growth and invasiveness of rheumatoid synovitis, and patients with a fibroblastic-rich pauci-immune pathotype respond poorly to currently approved antirheumatic drugs. Galectin-9 (Gal-9) has been reported to directly modulate rheumatoid arthritis (RA) FLSs and to hold both pro- and anti-inflammatory properties. The objective of this study was to evaluate clinical and pathogenic aspects of Gal-9 in RA, combining national patient cohorts and cellular models. Methods: Soluble Gal-9 was measured in plasma from patients with newly diagnosed, treatment-naïve RA (n = 98). The disease activity score 28-joint count C-reactive protein (DAS28CRP) and total Sharp score were used to evaluate the disease course serially over a two-year period. Plasma and synovial fluid samples were examined for soluble Gal-9 in patients with established RA (n = 18). A protein array was established to identify Gal-9 binding partners in the extracellular matrix (ECM). Synovial fluid mononuclear cells (SFMCs), harvested from RA patients, were used to obtain synovial-fluid derived FLSs (SF-FLSs) (n = 7). FLSs from patients suffering from knee Osteoarthritis (OA) were collected from patients when undergoing joint replacement surgery (n = 5). Monocultures of SF-FLSs (n = 6) and autologous co-cultures of SF-FLSs and peripheral blood mononuclear cells (PBMCs) were cultured with and without a neutralizing anti-Gal-9 antibody (n = 7). The mono- and co-cultures were subsequently analyzed by flow cytometry, MTT assay, and ELISA. Results: Patients with early and established RA had persistently increased plasma levels of Gal-9 compared with healthy controls (HC). The plasma levels of Gal-9 were associated with disease activity and remained unaffected when adding a TNF-inhibitor to their standard treatment. Gal-9 levels were elevated in the synovial fluid of established RA patients with advanced disease, compared with corresponding plasma samples. Gal-9 adhered to fibronectin, laminin and thrombospondin, while not to interstitial collagens in the ECM protein array. In vitro, a neutralizing Gal-9 antibody decreased MCP-1 and IL-6 production from both RA FLSs and OA FLSs. In co-cultures of autologous RA FLSs and PBMCs, the neutralization of Gal-9 also decreased MCP-1 and IL-6 production, without affecting the proportion of inflammatory FLSs. Conclusions: In RA, pretreatment plasma Gal-9 levels in early RA were increased and correlated with clinical disease activity. Gal-9 levels remained increased despite a significant reduction in the disease activity score in patients with early RA. The in vitro neutralization of Gal-9 decreased both MCP-1 and IL-6 production in an inflammatory subset of RA FLSs. Collectively these findings indicate that the persistent overexpression of Gal-9 in RA may modulate synovial FLS activities and could be involved in the maintenance of subclinical disease activity in RA.
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| 8. |
- Trollsås, M., et al.
(author)
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The influence of the molecular structure on the second-order nonlinear optical properties of pyroelectric liquid crystalline polymers
- 1998
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In: American Chemical Society Symposium Series (ACS). - Washington, DC : American Chemical Society. - 0097-6156 .- 1947-5918. ; 695, s. 315-327
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Journal article (peer-reviewed)abstract
- Pyroelectric Liquid Crystal Polymers (PLCP), a novel class of material with intrinsic polar order developed in our laboratory, are discussed. Thin films (2-4µm) of PLCP were prepared by photopolymerization of ferroelectric liquid crystalline monomers in the chiral smectic C (SmC*) phase. The poly(acrylate) materials have been structurally modified in order to improve their nonlinear optical and thermal properties. Further are their longterm nonlinear optical properties discussed based on results from second harmonic generation (SHG), spontaneous polarization (Ps), and dielectric spectroscopy.
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