Neuron–glia synapses in the brain: properties, diversity and functions of NG2 glia

e-Neuroforum ◽  
2015 ◽  
Vol 21 (3) ◽  
Author(s):  
Christian Steinhäuser ◽  
Dirk Dietrich

AbstractAlthough NG2 glial cells represent a frequent glial cell type in the brain, characterized by expression of the NG2 proteoglycan, the functional impact of these cells is still enigmatic. A large proportion of NG2 glia are proliferatively active throughout life. These cells express a plethora of ion channels and transmitter receptors, which enable them to detect neuronal activity. Intriguingly, NG2 glial cells receive synaptic input from glutamatergic and GABAergic neurons. Since these postsynaptic glial currents are very small, their spatial and temporal integration might play an important role. In white matter, most NG2 glial cells differentiate into oligodendrocytes and this process might be influenced through the activity of the aforementioned neuron-glia synapses. Increasing evidence suggests that the properties of NG2 glia vary across brain regions; however, the impact of this variability is not understood yet.

Author(s):  
Shawn D’Souza ◽  
Lisa Hirt ◽  
David R Ormond ◽  
John A Thompson

Abstract Gliomas are neoplasms that arise from glial cell origin and represent the largest fraction of primary malignant brain tumours (77%). These highly infiltrative malignant cell clusters modify brain structure and function through expansion, invasion and intratumoral modification. Depending on the growth rate of the tumour, location and degree of expansion, functional reorganization may not lead to overt changes in behaviour despite significant cerebral adaptation. Studies in simulated lesion models and in patients with stroke reveal both local and distal functional disturbances, using measures of anatomical brain networks. Investigations over the last two decades have sought to use diffusion tensor imaging tractography data in the context of intracranial tumours to improve surgical planning, intraoperative functional localization, and post-operative interpretation of functional change. In this study, we used diffusion tensor imaging tractography to assess the impact of tumour location on the white matter structural network. To better understand how various lobe localized gliomas impact the topology underlying efficiency of information transfer between brain regions, we identified the major alterations in brain network connectivity patterns between the ipsilesional versus contralesional hemispheres in patients with gliomas localized to the frontal, parietal or temporal lobe. Results were indicative of altered network efficiency and the role of specific brain regions unique to different lobe localized gliomas. This work draws attention to connections and brain regions which have shared structural susceptibility in frontal, parietal and temporal lobe glioma cases. This study also provides a preliminary anatomical basis for understanding which affected white matter pathways may contribute to preoperative patient symptomology.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nicole M. Wanner ◽  
Mathia Colwell ◽  
Chelsea Drown ◽  
Christopher Faulk

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively. Results F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms. Conclusions These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.


1955 ◽  
Vol 33 (3) ◽  
pp. 395-403 ◽  
Author(s):  
Irving H. Heller ◽  
K. A. C. Elliott

Per unit weight, cerebral and cerebellar cortex respire much more actively than corpus callosum. The rate per cell nucleus is highest in cerebral cortex, lower in corpus callosum, and still lower in cerebellar cortex. The oxygen uptake rates of the brain tumors studied, with the exception of an oligodendroglioma, were about the same as that of white matter on the weight basis but lower than that of cerebral cortex or white matter on the cell basis. In agreement with previous work, an oligodendroglioma respired much more actively than the other tumors. The rates of glycolysis of the brain tumors per unit weight were low but, relative to their respiration rate, glycolysis was higher than in normal gray or white matter. Consideration of the figures obtained leads to the following tentative conclusions: Glial cells of corpus callosum respire more actively than the neurons of the cerebellar cortex. Neurons of the cerebral cortex respire on the average much more actively than neurons of the cerebellar cortex or glial cells. Considerably more than 70% of the oxygen uptake by cerebral cortex is due to neurons. The oxygen uptake rates of normal oligodendroglia and astrocytes are probably about the same as the rates found per nucleus in an oligodendroglioma and in astrocytomas; oligodendroglia respire much more actively than astrocytes.


2021 ◽  
Vol 11 (10) ◽  
pp. 342-356
Author(s):  
T. Shulyatnikova ◽  
V. Tumanskiy

The aim of the study was to determine the immunohistochemical level of glutamine synthetase (GS) expression in different brain regions in the conditions of experimental acute liver failure in rats. Materials and methods. The study was conducted in Wistar rats: 5 sham (control) animals and 10 rats with acetaminophen induced liver failure model (AILF). The immunohistochemical study of GS expression in the sensorimotor cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen was carried out in the period of 12-24 h after acetaminophen treatment. Results. Beginning from the 6th hour after acetaminophen treatment all AILF-animals showed the progressive increase in clinical signs of acute brain disfunction finished in 6 rats by comatose state up to 24 h - they constituted subgroup AILF-B, “non-survived”. 4 animals survived until the 24 h - subgroup AILF-A, “survived”. In the AILF-B group, starting from 16 to 24 hours after treatment, a significant (relative to control) regionally-specific dynamic increase in the level of GS expression was observed in the brain: in the cortex – by 307.33 %, in the thalamus – by 249.47%, in the hippocampus – by 245.53%, in the subcortical white matter – by 126.08%, from 12th hour – in the caudate nucleus/putamen, by 191.66 %; with the most substantive elevation of GS expression in the cortex: by 4.07 times. Conclusion. Starting from the 16th hours after the acetaminophen treatment (from the 12th h in the caudate nucleus/putamen region) and up to 24 h, it is observed reliable compared to control dynamic increase in GS protein expression in the cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen of the rat brain with the most significant elevation in the cortex among other regions. The heterogeneity in the degree of GS expression rising in different brain regions potentially may indicate regions more permeable for ammonia and/or other systemic toxic factors as well as heterogeneous sensitivity of brain regions to deleterious agents in conditions of AILF. Subsequently, revealed diversity in the GS expression reflects the specificity of reactive response of local astroglia in the condition of AILF-encephalopathy during specific time-period. The dynamic increase in the GS expression associated with impairment of animal state, indicates involvement of increased GS levels in the mechanisms of experimental acute hepatic encephalopathy.


2017 ◽  
Vol 12 (01) ◽  
pp. 31 ◽  
Author(s):  
Jürg Kesselring ◽  

In recent years, enormous strides have been made in increasing the range and efficacy of disease-modifying drugs available for the treatment of multiple sclerosis (MS) in its early and remitting stages, and more continue to emerge. Another equally important concept of successful treatment of MS is neurorehabilitation, which must be pursued alongside these medications. Key factors that contribute to the impact of neurorehabilitation include resilience and neuroplasticity. In the former, components such as nutrition, self-belief and physical activity provide a stronger response to the disease and improved responses to treatment. Neuroplasticity is the capacity of the brain to establish new neuronal networks after lesion damage has occurred and distant brain regions assume control of lost functions. In MS, it is vital that each patient is treated by a coordinated multidisciplinary team. This enables all aspects of the disease including problems with mobility, gait, bladder/bowel disturbances, fatigue and depression to be effectively treated. It is also important that the treating team adopts current best practice and provides internationally agreed standards of care. A further vital aspect of MS management is patient engagement, in which individuals are fully involved and are encouraged to strive and put effort into meeting treatment goals. In this approach, healthcare providers become motivators and patients need less intervention and consume fewer resources. Numerous interventions that promote neurorehabilitation are available, though evidence to support their use is limited by a lack of data from large randomised controlled trials. Combining interventions that promote neurorehabilitation with newer, more effective treatments creates a promising potential to substantially improve the outlook for patients at all stages of MS.


2021 ◽  
Vol 10 (21) ◽  
pp. 4987
Author(s):  
Ronja Thieleking ◽  
Rui Zhang ◽  
Maria Paerisch ◽  
Kerstin Wirkner ◽  
Alfred Anwander ◽  
...  

In clinical diagnostics and longitudinal studies, the reproducibility of MRI assessments is of high importance in order to detect pathological changes, but developments in MRI hard- and software often outrun extended periods of data acquisition and analysis. This could potentially introduce artefactual changes or mask pathological alterations. However, if and how changes of MRI hardware, scanning protocols or preprocessing software affect complex neuroimaging outcomes from, e.g., diffusion weighted imaging (DWI) remains largely understudied. We therefore compared DWI outcomes and artefact severity of 121 healthy participants (age range 19–54 years) who underwent two matched DWI protocols (Siemens product and Center for Magnetic Resonance Research sequence) at two sites (Siemens 3T Magnetom Verio and Skyrafit). After different preprocessing steps, fractional anisotropy (FA) and mean diffusivity (MD) maps, obtained by tensor fitting, were processed with tract-based spatial statistics (TBSS). Inter-scanner and inter-sequence variability of skeletonised FA values reached up to 5% and differed largely in magnitude and direction across the brain. Skeletonised MD values differed up to 14% between scanners. We here demonstrate that DTI outcome measures strongly depend on imaging site and software, and that these biases vary between brain regions. These regionally inhomogeneous biases may exceed and considerably confound physiological effects such as ageing, highlighting the need to harmonise data acquisition and analysis. Future studies thus need to implement novel strategies to augment neuroimaging data reliability and replicability.


2021 ◽  
Author(s):  
Victor Nozais ◽  
Stephanie Forkel ◽  
Chris Foulon ◽  
Laurent Petit ◽  
Michel Thiebaut de Schotten

Abstract In recent years, the field of functional neuroimaging has moved from a pure localisationist approach of isolated functional brain regions to a more integrated view of those regions within functional networks. The methods used to investigate such networks, however, rely on local signals in grey matter and are limited in identifying anatomical circuitries supporting the interaction between brain regions. Mapping the brain circuits mediating the functional signal between brain regions would propel forward our understanding of the brain’s functional signatures and dysfunctions. We developed a novel method to unravel the relationship between brain circuits and functions: The Functionnectome. The Functionectome combines the functional signal from fMRI with the anatomy of white matter brain circuits to unlock and chart the first maps of functional white matter. To showcase the versatility of this new method, we provide the first functional white matter maps revealing the joint contribution of connected areas to motor, working memory, and language functions. The Functionnectome comes with an open source companion software and opens new avenues into studying functional networks by applying the method to already existing dataset and beyond task fMRI.


Author(s):  
Peggy Mason

With the knowledge acquired from this book, the brain regions responsible for each of the symptoms suffered by Jean-Dominique Bauby can be identified. It is also possible to understand why thought, language, and memory were unaffected in Bauby. Bauby’s narrative is used to launch a consideration of the role of embodiment in affective experience. The experience of Clive Wearing who, after a bout of encephalitis, was left without the ability to make new declarative memories is introduced to illustrate the highly personal and individual nature of people’s reactions to disease or clinical impairment. The impact of disease does not stop with the patient but extends to the patient’s loved ones and caregivers. This is particularly true of patients with dementia or those in an altered state of consciousness. Finally the reader is encouraged to use their understanding of the nervous system to provide compassionate care for patients.


2020 ◽  
Vol 4 (3) ◽  
pp. 761-787 ◽  
Author(s):  
Katharina Glomb ◽  
Emeline Mullier ◽  
Margherita Carboni ◽  
Maria Rubega ◽  
Giannarita Iannotti ◽  
...  

Recently, EEG recording techniques and source analysis have improved, making it feasible to tap into fast network dynamics. Yet, analyzing whole-cortex EEG signals in source space is not standard, partly because EEG suffers from volume conduction: Functional connectivity (FC) reflecting genuine functional relationships is impossible to disentangle from spurious FC introduced by volume conduction. Here, we investigate the relationship between white matter structural connectivity (SC) and large-scale network structure encoded in EEG-FC. We start by confirming that FC (power envelope correlations) is predicted by SC beyond the impact of Euclidean distance, in line with the assumption that SC mediates genuine FC. We then use information from white matter structural connectivity in order to smooth the EEG signal in the space spanned by graphs derived from SC. Thereby, FC between nearby, structurally connected brain regions increases while FC between nonconnected regions remains unchanged, resulting in an increase in genuine, SC-mediated FC. We analyze the induced changes in FC, assessing the resemblance between EEG-FC and volume-conduction- free fMRI-FC, and find that smoothing increases resemblance in terms of overall correlation and community structure. This result suggests that our method boosts genuine FC, an outcome that is of interest for many EEG network neuroscience questions.


2020 ◽  
Author(s):  
Tomas Fiala ◽  
Jihang Wang ◽  
Matthew Dunn ◽  
Peter Šebej ◽  
Se Joon Choi ◽  
...  

Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. These sensors, rendered highly lipophilic to anchor the conjugated pi-wire molecular framework in the membrane, offer several favorable functional parameters including fast response kinetics and high sensitivity to membrane potential changes. The impact of VSDs has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a non-genetic molecular platform for cell- and molecule-specific targeting of synthetic voltage sensitive dyes in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of voltage sensitive dyes by dynamic encapsulation, and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. We envision that modularity of our platform will enable its application to a variety of molecular targets and sensors, as well as lipophilic drugs and signaling modulators. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.


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