Neurite orientation dispersion and density imaging reveals white matter and hippocampal microstructure changes produced by Interleukin-6 in the TgCRND8 mouse model of amyloidosis

Colon-Perez, Luis M.; Ibanez, Kristen R.; Suarez, Mallory; K, Torroella; Acuna, Kelly; Ofori, Edward; Levites, Yona; Vaillancourt, David E.; Golde, Todd E.; Chakrabarty, Paramita; Febo, Marcelo

doi:10.1016/j.neuroimage.2019.116138

Cited by 39 publications

(39 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many laboratories in the field, including our own, have focused on responses of microglia to classic cytokines including but not limited to TNFα, IL1α, IL1β, IL10, IL6, and IFNγ (Chakrabarty et al, 2010(Chakrabarty et al, , 2011(Chakrabarty et al, , 2015Colon-Perez et al, 2019;Webers et al, 2020). Although these cytokines show massive changes in transcript in primary culture, in vivo transcript levels in the brain are very low throughout the lifespan of the non-Tg and Tg mice.…”

Section: Discussionmentioning

confidence: 99%

Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo

et al. 2021

Self Cite

View full text Add to dashboard Cite

Aggregation and accumulation of amyloid-β (Aβ) is a defining feature of Alzheimer’s disease pathology. To study microglial responses to Aβ, we applied exogenous Aβ peptide, in either oligomeric or fibrillar conformation, to primary mouse microglial cultures and evaluated system-level transcriptional changes and then compared these with transcriptomic changes in the brains of CRND8 APP mice. We find that primary microglial cultures have rapid and massive transcriptional change in response to Aβ. Transcriptomic responses to oligomeric or fibrillar Aβ in primary microglia, although partially overlapping, are distinct and are not recapitulated in vivo where Aβ progressively accumulates. Furthermore, although classic immune mediators show massive transcriptional changes in the primary microglial cultures, these changes are not observed in the mouse model. Together, these data extend previous studies which demonstrate that microglia responses ex vivo are poor proxies for in vivo responses. Finally, these data demonstrate the potential utility of using microglia as biosensors of different aggregate conformation, as the transcriptional responses to oligomeric and fibrillar Aβ can be distinguished.

show abstract

Section: Discussionmentioning

confidence: 99%

Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is unknown whether the observed between-group differences are unique to α-syn pathology compared with other proteinopathies. Reduced FA has been reported in Aβ ( Colon-Perez et al, 2019 ), tau ( Colgan et al, 2016 ), and SOD1 ( Marcuzzo et al, 2017 ) mouse models compared with controls. Also of note, areas of increased and reduced ALFF have been found in mild cognitive impairment and Alzheimer's disease patients ( Wang et al, 2011b ; Dai et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

α-Synuclein Induces Progressive Changes in Brain Microstructure and Sensory-Evoked Brain Function That Precedes Locomotor Decline

et al. 2020

Self Cite

View full text Add to dashboard Cite

In vivo functional and structural brain imaging of synucleinopathies in humans have provided a rich new understanding of the affected networks across the cortex and subcortex. Despite this progress, the temporal relationship between a-synuclein (a-syn) pathology and the functional and structural changes occurring in the brain is not well understood. Here, we examine the temporal relationship between locomotor ability, brain microstructure, functional brain activity, and a-syn pathology by longitudinally conducting rotarod, diffusion magnetic resonance imaging (MRI), resting-state functional MRI (fMRI), and sensory-evoked fMRI on 20 mice injected with a-syn fibrils and 20 PBS-injected mice at three timepoints (10 males and 10 females per group). Intramuscular injection of a-syn fibrils in the hindlimb of M83 1/2 mice leads to progressive a-syn pathology along the spinal cord, brainstem, and midbrain by 16 weeks post-injection. Our results suggest that peripheral injection of a-syn has acute systemic effects on the central nervous system such that structural and resting-state functional activity changes occur in the brain by four weeks post-injection, well before a-syn pathology reaches the brain. At 12 weeks post-injection, a separate and distinct pattern of structural and sensory-evoked functional brain activity changes was observed that are co-localized with previously reported regions of a-syn pathology and immune activation. Microstructural changes in the pons at 12 weeks post-injection were found to predict survival time and preceded measurable locomotor deficits. This study provides preliminary evidence for diffusion and fMRI markers linked to the progression of synuclein pathology and has translational importance for understanding synucleinopathies in humans.

show abstract

“…There are no theoretical restrictions for the application of HARDI or Q-ball imaging to animal cohort studies; however, there are many practical challenges such as scanning time. However, NODDI has been applied to detect neurite orientation dispersion of mouse brain microstructure (Wang et al, 2019 ) or alterations in hippocampal microstructure (Colon-Perez et al, 2019 ) and also to investigate spinal cords at 17.6 T in an ALS mouse model (G93A-SOD1 mice) for the detection of presymptomatic axonal degeneration (Gatto et al, 2018d ). Because simple Gaussian diffusion models do not sufficiently describe water diffusion in complex tissues, a novel diffusion MRI acquisition approach can be applied, that is, hybrid diffusion imaging (HYDI).…”

Section: Discussionmentioning

confidence: 99%

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

et al. 2020

View full text Add to dashboard Cite

The understanding of human and non-human microstructural brain alterations in the course of neurodegenerative diseases has substantially improved by the non-invasive magnetic resonance imaging (MRI) technique of diffusion tensor imaging (DTI). Animal models (including disease or knockout models) allow for a variety of experimental manipulations, which are not applicable to humans. Thus, the DTI approach provides a promising tool for cross-species cross-sectional and longitudinal investigations of the neurobiological targets and mechanisms of neurodegeneration. This overview with a systematic review focuses on the principles of DTI analysis as used in studies at the group level in living preclinical models of neurodegeneration. The translational aspect from in-vivo animal models toward (clinical) applications in humans is covered as well as the DTI-based research of the non-human brains' microstructure, the methodological aspects in data processing and analysis, and data interpretation at different abstraction levels. The aim of integrating DTI in multiparametric or multimodal imaging protocols will allow the interrogation of DTI data in terms of directional flow of information and may identify the microstructural underpinnings of neurodegeneration-related patterns.

show abstract

Neurite orientation dispersion and density imaging reveals white matter and hippocampal microstructure changes produced by Interleukin-6 in the TgCRND8 mouse model of amyloidosis

Cited by 39 publications

References 89 publications

Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo

Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo

α-Synuclein Induces Progressive Changes in Brain Microstructure and Sensory-Evoked Brain Function That Precedes Locomotor Decline

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

Contact Info

Product

Resources

About