Biology subjects

Vaas, M.

Publications and source records attributed to Vaas, M..

4 recordsLinked to original sources

bioRxiv2021

Non-invasive visualization of amyloid-beta deposits in Alzheimer amyloidosis mice using magnetic resonance imaging and fluorescence molecular tomography

Abnormal cerebral accumulation of amyloid-beta peptide (A{beta}) is a major hallmark of Alzheimers disease. Non-invasive monitoring of A{beta} deposits enables assessing the disease burden in patients and animal models mimicking aspects of the human disease as well as evaluating the efficacy of A{beta}-modulating therapies. Previous in vivo assessments of plaque load in mouse models of cerebral amyloidosis have been predominantly based on two-dimensional diffuse fluorescence reflectance imaging (2D-FRI) and two-photon microscopy (2PM) using A{beta}-specific imaging agents. However, 2D-FRI lacks depth resolution, whereas 2PM is restricted by the limited field of view preventing coverage of large brain regions. Here, we utilized a magnetic resonance imaging (MRI) and fluorescence molecular tomography (FMT) pipeline with the curcumin derivative fluorescent probe CRANAD-2 to achieve full 3D brain coverage for detecting A{beta} accumulation in the arcA{beta} mouse model of cerebral amyloidosis. A homebuilt FMT system was used for data acquisition in combination with a customized software platform enabling the integration of anatomical information derived from MRI as prior information for FMT image reconstruction. The results obtained from the FMT-MRI study were compared to data obtained from conventional 2D-FRI recorded under similar physiological conditions. The two methods yielded comparable time courses of the fluorescence intensity following intravenous injection of CRANAD-2 in a region of interest comprising the mouse brain. The depth resolution inherent to FMT allowed separation of signal contributions from the scalp and different brain regions, indicating preferential accumulation of the fluorescent tracer in the cerebral cortex, a region characterized by significant plaque deposition in arc A{beta} mice. In conclusion, we have demonstrated the feasibility of visualizing A{beta} deposition in 3D using a multimodal FMT-MRI method. This hybrid imaging method provides complementary anatomical, physiological and molecular information, thereby enabling the detailed characterization of the disease status in mouse models of cerebral amyloidosis, which is also important for monitoring the efficacy of putative treatments targeting A{beta}.

neuroscience↗

bioRxiv2021

In vivo imaging of cannabinoid type 2 receptors, functional and structural alterations in mouse model of cerebral ischemia by PET and MRI

Background and purposeBrain ischemia is one of the most important pathologies of the central nervous system. Non-invasive molecular imaging methods have the potential to provide critical insights into the temporal dynamics and follow alterations of receptor expression and metabolism in ischemic stroke. The aim of this study was to assess the cannabinoid type 2 receptors (CB2R) levels in transient middle cerebral artery occlusion (tMCAO) mouse models at subacute stage using positron emission tomography (PET) with our novel tracer [18F]RoSMA-18-d6, and structural imaging by magnetic resonance imaging (MRI). MethodsOur recently developed CB2R PET tracer [18F]RoSMA-18-d6 was used for imaging the neuroinflammation at 24 h after reperfusion in tMCAO mice. The RNA expression levels of CB2R and other inflammatory markers were analyzed by quantitative real-time polymerase chain reaction using brain tissues from tMCAO (1 h occlusion) and sham-operated mice. [18F]fluorodeoxyglucose (FDG) was included for evaluation of the cerebral metabolic rate of glucose (CMRglc). In addition, diffusion-weighted imaging and T2-weighted imaging were performed for anatomical reference and delineating the lesion in tMCAO mice. ResultsmRNA expressions of inflammatory markers TNF-, Iba1, MMP9 and GFAP, CNR2 were increased at 24 h after reperfusion in the ipsilateral compared to contralateral hemisphere of tMCAO mice, while mRNA expression of the neuronal marker MAP-2 was markedly reduced. Reduced [18F]FDG uptake was observed in the ischemic striatum of tMCAO mouse brain at 24 h after reperfusion. Although higher activity of [18F]RoSMA-18-d6 in ex-vivo biodistribution studies and higher standard uptake value ratio (SUVR) were detected in the ischemic ipsilateral compared to contralateral striatum in tMCAO mice, the in-vivo specificity of [18F]RoSMA-18-d6 was confirmed only in the CB2R-rich spleen. ConclusionsThis study revealed an increased [18F]RoSMA-18-d6 measure of CB2R and a reduced [18F]FDG measure of CMRglc in ischemic striatum of tMCAO mice at subacute stage. [18F]RoSMA-18-d6 might be a promising PET tracer for detecting CB2R alterations in animal models of neuroinflammation without neuronal loss.

neuroscience↗

bioRxiv2020

In-vitro and in-vivo characterization of CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of amyloid-beta deposits in Alzheimer mice

The abnormal deposition of fibrillar beta-amyloid (A{beta}) deposits in the brain is one of the major histopathological hallmarks of Alzheimers disease (AD). Here we characterize curcumin-derivative CRANAD-2 for multi-spectral optoacoustic tomography (MSOT) and fluorescence imaging of brain A{beta} deposits in the arcA{beta} mouse model of AD cerebral amyloidosis. CRANAD-2 shows a specific and quantitative detection of A fibrils in vitro, even in complex mixtures, and it is capable to distinguish between monomeric and fibrillar forms of A. In vivo epifluorescence and MSOT after intravenous CRANAD-2 administration demonstrated higher retention in arcA{beta} compared to non-transgenic littermate mice. Immunohistochemistry showed co-localization of CRANAD-2 and A{beta} deposits in arcA{beta} mouse brain sections, thus verifying the specificity of the probe. In conclusion, we demonstrate suitability of CRANAD-2 for fluorescence- and MSOT-based detection of A{beta} deposits in animal models of AD pathology, which facilitates mechanistic studies and the monitoring of putative treatments targeting A{beta} deposits.

neuroscience↗

bioRxiv2020

Blocking gephyrin phosphorylation or microglia BDNF signaling prevents synapse loss and reduces infarct volume after ischemia

Microglia interact with neurons to facilitate synapse plasticity; however, signal transducers between microglia and neuron remain unknown. Here, using in vitro organotypic hippocampal slice cultures and transient MCAO in genetically-engineered mice in vivo, we report that at 24 h post-ischemia microglia release BDNF to downregulate glutamatergic and GABAergic synapses within the peri-infarct area. Analysis of the CA1 hippocampal formation in vitro shows that proBDNF and mBDNF downregulate glutamatergic dendritic spines and gephyrin scaffold stability through p75NTR and TrkB receptors respectively. Post-MCAO, we report that in the peri- infarct area and in the corresponding contralateral hemisphere similar neuroplasticity occur through microglia activation and gephyrin phosphorylation at Ser268, Ser270 in vivo. Targeted deletion of the Bdnf gene in microglia or GphnS268A/S270A (phospho-null) point-mutations protect against ischemic brain damage, neuroinflamation and synapse downregulation normally seen post-MCAO. Collectively, we report that gephyrin phosphorylation and microglia derived BDNF faciliate synapse plasticity after transient ischemia.

neuroscience↗