Dataset Information

Microglial Density Alters Measures of Axonal Integrity and Structural Connectivity.

ABSTRACT: Diffusion tensor imaging (DTI) has fundamentally transformed how we interrogate diseases and disorders of the brain in neuropsychiatric illness. DTI and recently developed multicompartment diffusion-weighted imaging (MC-DWI) techniques, such as NODDI (neurite orientation dispersion and density imaging), measure diffusion anisotropy presuming a static neuroglial environment; however, microglial morphology and density are highly dynamic in psychiatric illness, and how alterations in microglial density might influence intracellular measures of diffusion anisotropy in DTI and MC-DWI brain microstructure is unknown. To address this question, DTI and MC-DWI studies of murine brains depleted of microglia were performed, revealing significant alterations in axonal integrity and fiber tractography in DTI and in commonly used MC-DWI models. With accumulating evidence of the role of microglia in neuropsychiatric illness, our findings uncover the unexpected contribution of microglia to measures of axonal integrity and structural connectivity and provide unanticipated insights into the potential influence of microglia in diffusion imaging studies of neuropsychiatric disease.

SUBMITTER: Yi SY

PROVIDER: S-EPMC7709542 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Microglial Density Alters Measures of Axonal Integrity and Structural Connectivity.

Yi Sue Y SY Stowe Nicholas A NA Barnett Brian R BR Dodd Keith K Yu John-Paul J JJ

Biological psychiatry. Cognitive neuroscience and neuroimaging 20200424 11

Diffusion tensor imaging (DTI) has fundamentally transformed how we interrogate diseases and disorders of the brain in neuropsychiatric illness. DTI and recently developed multicompartment diffusion-weighted imaging (MC-DWI) techniques, such as NODDI (neurite orientation dispersion and density imaging), measure diffusion anisotropy presuming a static neuroglial environment; however, microglial morphology and density are highly dynamic in psychiatric illness, and how alterations in microglial den ...[more]

PMID: 32507509

Similar Datasets

Project description:Neurons innervate space by extending axonal and dendritic arborizations. When axons and dendrites come in close proximity of each other, synapses between neurons can be formed. Neurons vary greatly in their morphologies and synaptic connections with other neurons. The size and shape of the arborizations determine the way neurons innervate space. A neuron may therefore be characterized by the spatial distribution of its axonal and dendritic "mass." A population mean "mass" density field of a particular neuron type can be obtained by averaging over the individual variations in neuron geometries. Connectivity in terms of candidate synaptic contacts between neurons can be determined directly on the basis of their arborizations but also indirectly on the basis of their density fields. To decide when a candidate synapse can be formed, we previously developed a criterion defining that axonal and dendritic line pieces should cross in 3D and have an orthogonal distance less than a threshold value. In this paper, we developed new methodology for applying this criterion to density fields. We show that estimates of the number of contacts between neuron pairs calculated from their density fields are fully consistent with the number of contacts calculated from the actual arborizations. However, the estimation of the connection probability and the expected number of contacts per connection cannot be calculated directly from density fields, because density fields do not carry anymore the correlative structure in the spatial distribution of synaptic contacts. Alternatively, these two connectivity measures can be estimated from the expected number of contacts by using empirical mapping functions. The neurons used for the validation studies were generated by our neuron simulator NETMORPH. An example is given of the estimation of average connectivity and Euclidean pre- and postsynaptic distance distributions in a network of neurons represented by their population mean density fields.

Project description:ObjectivesRecovery from coma might critically depend on the structural and functional integrity of frontoparietal networks. We aimed to measure this integrity in traumatic brain injury and anoxo-ischemic (cardiac arrest) coma patients by using an original multimodal MRI protocol.DesignProspective cohort study.SettingThree Intensive Critical Care Units affiliated to the University in Toulouse (France).PatientsWe longitudinally recruited 43 coma patients (Glasgow Coma Scale at the admission < 8; 29 cardiac arrest and 14 traumatic brain injury) and 34 age-matched healthy volunteers. Exclusion criteria were disorders of consciousness lasting more than 30 days and focal brain damage within the explored brain regions. Patient assessments were conducted at least 2 days (5 ± 2 d) after complete withdrawal of sedation. All patients were followed up (Coma Recovery Scale-Revised) 3 months after acute brain injury.InterventionsNone.Measurements and main resultsFunctional and structural MRI data were recorded, and the analysis was targeted on the posteromedial cortex, the medial prefrontal cortex, and the cingulum. Univariate analyses and machine learning techniques were used to assess diagnostic and predictive values. Coma patients displayed significantly lower medial prefrontal cortex-posteromedial cortex functional connectivity (area under the curve, 0.94; 95% CI, 0.93-0.95). Cardiac arrest patients showed specific structural disturbances within posteromedial cortex. Significant cingulum architectural disturbances were observed in traumatic brain injury patients. The machine learning medial prefrontal cortex-posteromedial cortex multimodal classifier had a significant predictive value (area under the curve, 0.96; 95% CI, 0.95-0.97), best combination of subregions that discriminates a binary outcome based on Coma Recovery Scale-Revised).ConclusionsThis exploratory study suggests that frontoparietal functional disconnections are specifically observed in coma and their structural counterpart provides information about brain injury mechanisms. Multimodal MRI biomarkers of frontoparietal disconnection predict 3-month outcome in our sample. These findings suggest that fronto-parietal disconnection might be particularly relevant for coma outcome prediction and could inspire innovative precision medicine approaches.

Project description:A global top priority for ameliorating male factor infertility includes identification of environmental factors and mechanisms that impact sperm function. Detection of endocrine disruptors (EDs) in seminal plasma and within the female reproductive tract has created an urgent need to understand how environmental stressors alter postejaculatory sperm function. Tributyltin chloride (TBT) is a model organotin, ED and epigenetic modifier that causes reproductive disorders in testicular sperm; however, consequences of TBT exposure on postejaculatory sperm prior to fertilization remain unknown. Our previous data indicate that TBT-exposed sperm affects initial cleavage and lowers embryo development potential. However, identifying reasons for idiopathic male factor subfertility is challenged by lack of routine clinical assessment for subtle phenotypes that compromise sperm function and therefore remain undetected with current diagnostic tools. Results The present study was aimed at identifying structural, genomic, and epigenomic consequences of TBT exposure to postejaculatory sperm in a temporal manner reflective of sperm transport prior to fertilization within the female reproductive tract. Bovine sperm were exposed to TBT (0 ,1, 10, 100nM) for 24 h under non-capacitating conditions at 25°C followed by quantification of sperm kinematics at 37°C, DNA integrity, and methylation status. No differences in sperm kinematics or capacitation status were detected after 24 h. However, acrosome integrity was compromised at both 0 and 24 h (P ≤ 0.05). Sperm DNA integrity was also negatively affected after 24 h. The methylation levels of select loci were quantified by PacBio single-molecule real-time (SMRT) long-read high-fidelity sequencing. Whole genome methyl-seq revealed 750 differentially methylated regions (DMRs) associated with exposure to TBT for 24 h. IPA and GO analyses identified embryo development, cell signaling, and transcriptional regulation as the most relevant bio-functions of TBT altered DMRs. Conclusions Postejaculatory mammalian sperm exposure to TBT negatively affects parameters important for sperm function while altering DNA integrity and the methylation profile of promotor regions. Consequences of sperm exposure to TBT include cellular and molecular mechanisms that are important for sperm function but remain undetected by routine clinical analyses. These findings provided new insight towards environmental impacts on postejaculatory sperm function.

Dataset Information

Microglial Density Alters Measures of Axonal Integrity and Structural Connectivity.

Publications

Microglial Density Alters Measures of Axonal Integrity and Structural Connectivity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets