Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain

Detrez, Jan R.; Maurin, Hervé; Kolen, Kristof Van; Willems, Roland; Colombelli, Julien; Lechat, Benoit; Roucourt, Bart; Leuven, Fred Van; Baatout, Sarah; Larsen, Peter H.; Nuydens, Rony; Timmermans, Jean‐Pierre; Vos, Winnok H. De

doi:10.1016/j.nbd.2019.03.010

Cited by 30 publications

(34 citation statements)

References 59 publications

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“…Among the various techniques available, immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO) has emerged as a simple and rapid method for achieving good antibody penetration and tissue clearing (Liebmann et al, 2016; Renier et al, 2014; Renier et al, 2016). iDISCO–LSFM is particularly useful for CNS research as the low brain anatomical variation between individual mice allows scanned brains to be mapped onto a common coordinated framework (CCF) for subsequent unbiased quantitative image analysis of immune-labeled molecular targets (Detrez et al, 2019; Hasegawa et al, 2019; Henning et al, 2019; Kjaergaard et al, 2019; Liebmann et al, 2016; Merz et al, 2019; Mzinza et al, 2018; Renier et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Quantitative whole-brain 3D imaging of tyrosine hydroxylase-labeled neuron architecture in the mouse MPTP model of Parkinson's disease

Roostalu

Salinas

Thorbek

et al. 2019

Disease Models &Amp; Mechanisms

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Parkinson's disease (PD) is a basal ganglia movement disorder characterized by progressive degeneration of the nigrostriatal dopaminergic system. Immunohistochemical methods have been widely used for characterization of dopaminergic neuronal injury in animal models of PD, including the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. However, conventional immunohistochemical techniques applied to tissue sections have inherent limitations with respect to loss of 3D resolution, yielding insufficient information on the architecture of the dopaminergic system. To provide a more comprehensive and non-biased map of MPTP-induced changes in central dopaminergic pathways, we used iDISCO immunolabeling, light-sheet fluorescence microscopy (LSFM) and deep-learning computational methods for whole-brain three-dimensional visualization and automated quantitation of tyrosine hydroxylase (TH)-positive neurons in the adult mouse brain. Mice terminated 7 days after acute MPTP administration demonstrated widespread alterations in TH expression. Compared to vehicle controls, MPTP-dosed mice showed a significant loss of TH-positive neurons in the substantia nigra pars compacta and ventral tegmental area. Also, MPTP dosing reduced overall TH signal intensity in basal ganglia nuclei, i.e. the substantia nigra, caudate-putamen, globus pallidus and subthalamic nucleus. In contrast, increased TH signal intensity was predominantly observed in limbic regions, including several subdivisions of the amygdala and hypothalamus. In conclusion, mouse whole-brain 3D imaging is ideal for unbiased automated counting and densitometric analysis of TH-positive cells. The LSFM–deep learning pipeline tracked brain-wide changes in catecholaminergic pathways in the MPTP mouse model of PD, and may be applied for preclinical characterization of compounds targeting dopaminergic neurotransmission.

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Section: Introductionmentioning

confidence: 99%

Quantitative whole-brain 3D imaging of tyrosine hydroxylase-labeled neuron architecture in the mouse MPTP model of Parkinson's disease

Roostalu

Salinas

Thorbek

et al. 2019

Disease Models &Amp; Mechanisms

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show abstract

“…Regional analysis of the EGFP and mCitrine expression was done as previously described [31]. Briefly, the autofluorescence channel was aligned to a 3D autofluorescence reference brain atlas (Allen Brain atlas) using Elastix, and the resulting transformation vector was used for regional analysis of the fluorescent protein signal [32].…”

Section: Methodsmentioning

confidence: 99%

Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity

Peeters

Hinz

Detrez

et al. 2019

Preprint

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29The anterior cingulate area (ACA) is an integral part of the prefrontal cortex in mice and has been 30 implicated in several cognitive functions. Previous anatomical and functional imaging studies 31 demonstrated that the ACA is highly interconnected with numerous brain regions acting as a hub region 32 in functional networks. However, the importance of the ACA in regulating functional network activity and 33 connectivity remains to be elucidated. Recently developed neuromodulatory techniques, such as Designer 34Receptors Exclusively Activated by Designer Drugs (DREADDs) allow for precise control of neuronal 35 activity. In this study, we used an inhibitory kappa-opioid receptor DREADDs (KORD) to temporally inhibit 36 neuronal firing in the right ACA of mice and assessed functional network activity and connectivity using 37 non-invasive functional MRI. We demonstrated that KORD-induced inhibition of the right ACA induced 38 blood oxygenation-level dependent (BOLD) signal decreases and increases in connected brain regions 39 throughout of hemispheres. Furthermore, these modulations in neuronal activity were associated with 40 decreased intra-and interhemispheric functional connectivity. These results demonstrate that the 41 combination of the DREADD technology and non-invasive functional imaging methods is a valuable tool 42 for unraveling the underlying mechanisms of network function and dysfunction. 43 44 45 Receptors Exclusively Activated by Designer Drugs (DREADDs), which are engineered receptors for 63 targeted enhancement or silencing of neurons upon binding of an otherwise inert ligand. The combination 64 of chemogenetics and non-invasive neuroimaging methods, such as functional magnetic resonance 65 imaging (fMRI), allows direct evaluation of DREADD-induced changes in neuronal firing on large-scale 66 neuronal activity and FC. As such, Giorgi et al. were able to causally link the chemogenetic activation of 67serotonergic neurons with neuronal activity increases in cortical and subcortical brain areas, measured by 68 relative cerebral blood volume increases [23]. Furthermore, other studies also used blood-oxygenation-69

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“…A delivery system that slowly releases IL-13 in the CNS could be utilized for a variety of applications. Since any injection into the brain results in a needle stick injury, whereby macrophages and microglia invade the injection tract (an event which is seen even when injecting only sterile saline 46 ), such a sustained-release system could be used as an adjuvant for regenerative medicine and cell transplantation strategies. The microglial/macrophage response associated with the stereotactic injection is typically pro-inflammatory in nature, 9,47 adding a greater burden to the brain region undergoing treatment.…”

Section: Immunomodulatory Activity Of Il-13 Functionalized Cryogels Imentioning

confidence: 99%

Heparin-based, injectable microcarriers for controlled delivery of interleukin-13 to the brain

et al. 2020

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Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain

Cited by 30 publications

References 59 publications

Quantitative whole-brain 3D imaging of tyrosine hydroxylase-labeled neuron architecture in the mouse MPTP model of Parkinson's disease

Quantitative whole-brain 3D imaging of tyrosine hydroxylase-labeled neuron architecture in the mouse MPTP model of Parkinson's disease

Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity

Heparin-based, injectable microcarriers for controlled delivery of interleukin-13 to the brain

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