scholarly journals Focal Loss of the Paranodal Domain Protein Neurofascin155 in the Internal Capsule Impairs Cortically Induced Muscle Activity in Vivo.

2020 ◽  
Author(s):  
Kazuo Kunisawa ◽  
Nobuhiko Hatanaka ◽  
Takeshi Shimizu ◽  
Kenta Kobayashi ◽  
Yasuyuki Osanai ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Internal Capsule ◽  
Triceps Brachii ◽  
Myelinated Axons ◽  
Electrophysiological Properties ◽  
Motor Behaviors ◽  
Paranodal Junctions ◽  
The Central Nervous System ◽  
The Impact

Abstract Paranodal axoglial junctions are essential for rapid nerve conduction and the organization of axonal domains in myelinated axons. Neurofascin155 (Nfasc155) is a glial cell adhesion molecule that is also required for the assembly of these domains. Previous studies have demonstrated that general ablation of Nfasc155 disorganizes these domains, reduces conduction velocity, and disrupts motor behaviors. Multiple sclerosis (MS), a typical disorder of demyelination in the central nervous system, is reported to have autoantibody to Nfasc155. However, the impact of focal loss of Nfasc155, which may occur in MS patients, remains unclear. Here, we examined whether restricted focal loss of Nfasc155 affects the electrophysiological properties of the motor system in vivo. Adeno-associated virus type5 (AAV5) harboring EGFP-2A-Cre was injected into the glial-enriched internal capsule of floxed-Neurofascin (NfascFlox/Flox) mice to focally disrupt paranodal junctions in the cortico-fugal fibers from the motor cortex to the spinal cord. Electromyograms (EMGs) of the triceps brachii muscles in response to electrical stimulation of the motor cortex were successively examined in these awake mice. EMG analysis showed significant delay in the onset and peak latencies after AAV injection compared to control (Nfasc+/+) mice. Moreover, EMG half-widths were increased, and EMG amplitudes were gradually decreased by 13 weeks. Similar EMG changes have been reported in MS patients. These findings provide physiological evidence that motor outputs are obstructed by focal ablation of paranodal junctions in myelinated axons. Our findings may open a new path toward development of a novel biomarker for an early phase of human MS, as Nfasc155 detects microstructural changes in the paranodal junction.

scholarly journals Focal loss of the paranodal domain protein Neurofascin155 in the internal capsule impairs cortically induced muscle activity in vivo

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Kazuo Kunisawa ◽  
Nobuhiko Hatanaka ◽  
Takeshi Shimizu ◽  
Kenta Kobayashi ◽  
Yasuyuki Osanai ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Internal Capsule ◽  
Triceps Brachii ◽  
Myelinated Axons ◽  
Electrophysiological Properties ◽  
Motor Behaviors ◽  
Paranodal Junctions ◽  
The Central Nervous System ◽  
The Impact

AbstractParanodal axoglial junctions are essential for rapid nerve conduction and the organization of axonal domains in myelinated axons. Neurofascin155 (Nfasc155) is a glial cell adhesion molecule that is also required for the assembly of these domains. Previous studies have demonstrated that general ablation of Nfasc155 disorganizes these domains, reduces conduction velocity, and disrupts motor behaviors. Multiple sclerosis (MS), a typical disorder of demyelination in the central nervous system, is reported to have autoantibody to Nfasc. However, the impact of focal loss of Nfasc155, which may occur in MS patients, remains unclear. Here, we examined whether restricted focal loss of Nfasc155 affects the electrophysiological properties of the motor system in vivo. Adeno-associated virus type5 (AAV5) harboring EGFP-2A-Cre was injected into the glial-enriched internal capsule of floxed-Neurofascin (NfascFlox/Flox) mice to focally disrupt paranodal junctions in the cortico-fugal fibers from the motor cortex to the spinal cord. Electromyograms (EMGs) of the triceps brachii muscles in response to electrical stimulation of the motor cortex were successively examined in these awake mice. EMG analysis showed significant delay in the onset and peak latencies after AAV injection compared to control (Nfasc+/+) mice. Moreover, EMG half-widths were increased, and EMG amplitudes were gradually decreased by 13 weeks. Similar EMG changes have been reported in MS patients. These findings provide physiological evidence that motor outputs are obstructed by focal ablation of paranodal junctions in myelinated axons. Our findings may open a new path toward development of a novel biomarker for an early phase of human MS, as Nfasc155 detects microstructural changes in the paranodal junction.

Effects of CSF Properties on Brain Response Under Impact Loading

2009 ◽  
Author(s):  
M. S. Chafi ◽  
V. Dirisala ◽  
G. Karami ◽  
M. Ziejewski
Keyword(s):  
Human Head ◽  
Brain Response ◽  
Pia Mater ◽  
Mechanical Shocks ◽  
The Central Nervous System ◽  
Simultaneous Loading ◽  
The Impact ◽  
Impact Experiments ◽  
The Brain

In the central nervous system, the subarachnoid space is the interval between the arachnoid membrane and the pia mater. It is filled with a clear, watery liquid called cerebrospinal fluid (CSF). The CSF buffers the brain against mechanical shocks and creates buoyancy to protect it from the forces of gravity. The relative motion of the brain due to a simultaneous loading is caused because the skull and brain have different densities and the CSF surrounds the brain. The impact experiments are usually carried out on cadavers with no CSF included because of the autolysis. Even in the cadaveric head impact experiments by Hardy et al. [1], where the specimens are repressurized using artificial CSF, this is not known how far this can replicate the real functionality of CSF. With such motivation, a special interest lies on how to model this feature in a finite element (FE) modeling of the human head because it is questionable if one uses in vivo CSF properties (i.e. bulk modulus of 2.19 GPa) to validate a FE human head against cadaveric experimental data.

scholarly journals Bundle-Specific Axon Diameter Index as a New Contrast to Differentiate White Matter Tracts

2021 ◽  
Vol 15 ◽  
Author(s):  
Muhamed Barakovic ◽  
Gabriel Girard ◽  
Simona Schiavi ◽  
David Romascano ◽  
Maxime Descoteaux ◽  
...  
Keyword(s):  
White Matter ◽  
Internal Capsule ◽  
Mean Value ◽  
Axon Diameter ◽  
Posterior Limb ◽  
Weighted Magnetic Resonance Imaging ◽  
The Central Nervous System ◽  
Index Value ◽  
White Matter Connectivity

In the central nervous system of primates, several pathways are characterized by different spectra of axon diameters. In vivo methods, based on diffusion-weighted magnetic resonance imaging, can provide axon diameter index estimates non-invasively. However, such methods report voxel-wise estimates, which vary from voxel-to-voxel for the same white matter bundle due to partial volume contributions from other pathways having different microstructure properties. Here, we propose a novel microstructure-informed tractography approach, COMMITAxSize, to resolve axon diameter index estimates at the streamline level, thus making the estimates invariant along trajectories. Compared to previously proposed voxel-wise methods, our formulation allows the estimation of a distinct axon diameter index value for each streamline, directly, furnishing a complementary measure to the existing calculation of the mean value along the bundle. We demonstrate the favourable performance of our approach comparing our estimates with existing histologically-derived measurements performed in the corpus callosum and the posterior limb of the internal capsule. Overall, our method provides a more robust estimation of the axon diameter index of pathways by jointly estimating the microstructure properties of the tissue and the macroscopic organisation of the white matter connectivity.

scholarly journals The multicellular interplay of microglia in health and disease: lessons from leukodystrophy

2021 ◽  
Vol 14 (8) ◽  
Author(s):  
Woutje M. Berdowski ◽  
Leslie E. Sanderson ◽  
Tjakko J. van Ham
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
Genetic Disorders ◽  
Brain Dysfunction ◽  
Brain Diseases ◽  
Human Patient ◽  
The Central Nervous System ◽  
The Impact

ABSTRACT Microglia are highly dynamic cells crucial for developing and maintaining lifelong brain function and health through their many interactions with essentially all cellular components of the central nervous system. The frequent connection of microglia to leukodystrophies, genetic disorders of the white matter, has highlighted their involvement in the maintenance of white matter integrity. However, the mechanisms that underlie their putative roles in these processes remain largely uncharacterized. Microglia have also been gaining attention as possible therapeutic targets for many neurological conditions, increasing the demand to understand their broad spectrum of functions and the impact of their dysregulation. In this Review, we compare the pathological features of two groups of genetic leukodystrophies: those in which microglial dysfunction holds a central role, termed ‘microgliopathies’, and those in which lysosomal or peroxisomal defects are considered to be the primary driver. The latter are suspected to have notable microglia involvement, as some affected individuals benefit from microglia-replenishing therapy. Based on overlapping pathology, we discuss multiple ways through which aberrant microglia could lead to white matter defects and brain dysfunction. We propose that the study of leukodystrophies, and their extensively multicellular pathology, will benefit from complementing analyses of human patient material with the examination of cellular dynamics in vivo using animal models, such as zebrafish. Together, this will yield important insight into the cell biological mechanisms of microglial impact in the central nervous system, particularly in the development and maintenance of myelin, that will facilitate the development of new, and refinement of existing, therapeutic options for a range of brain diseases.

scholarly journals Adverse Effects of Methylene Blue on the Central Nervous System

2008 ◽  
Vol 108 (4) ◽  
pp. 684-692 ◽  
Author(s):  
Laszlo Vutskits ◽  
Adrian Briner ◽  
Paul Klauser ◽  
Eduardo Gascon ◽  
Alexandre G. Dayer ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Cell Death ◽  
Neuronal Cultures ◽  
Dendritic Arbor ◽  
Field Potentials ◽  
Neurotoxic Effects ◽  
The Central Nervous System ◽  
The Impact

Background An increasing number of clinical observations suggest adverse neurologic outcome after methylene blue (MB) infusion in the setting of parathyroid surgery. Hence, the aim of the current study was to investigate the potentially neurotoxic effects of MB using a combination of in vivo and in vitro experimental approaches. Methods Isoflurane-anesthetized adult rats were used to evaluate the impact of a single bolus intravascular administration of MB on systemic hemodynamic responses and on the minimum alveolar concentration (MAC) of isoflurane using the tail clamp test. In vivo, MB-induced cell death was evaluated 24 h after MB administration using Fluoro-Jade B staining and activated caspase-3 immunohistochemistry. In vitro, neurotoxic effects of MB were examined in hippocampal slice cultures by measuring excitatory field potentials as well as propidium iodide incorporation after MB exposure. The impact of MB on dendritic arbor was evaluated in differentiated single cell neuronal cultures. Results Bolus injections of MB significantly reduced isoflurane MAC and initiated widespread neuronal apoptosis. Electrophysiologic recordings in hippocampal slices revealed a rapid suppression of evoked excitatory field potentials by MB, and this was associated with a dose-dependent effect of this drug on cell death. Dose-response experiments in single cell neuronal cultures revealed that a 2-h-long exposure to MB at non-cell-death-inducing concentrations could still induce significant retraction of dendritic arbor. Conclusions These results suggest that MB exerts neurotoxic effects on the central nervous system and raise questions regarding the safety of using this drug at high doses during parathyroid gland surgery.

Advances in Imaging Multiple Sclerosis

2017 ◽  
Vol 37 (05) ◽  
pp. 538-545 ◽  
Author(s):  
Eduardo Caverzasi ◽  
Christian Cordano ◽  
Stephen Hauser ◽  
Roland Henry ◽  
Antje Bischof
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Emission Tomography ◽  
Resonance Imaging ◽  
Ms Imaging ◽  
Positron Emission ◽  
The Central Nervous System ◽  
The Impact

Neuroimaging has emerged as a powerful technology that has enabled visualization of the impact of multiple sclerosis (MS) on the central nervous system in vivo with unprecedented precision. It has played a crucial role in disentangling the chronology of inflammation and neurodegeneration, developing and understanding mechanisms of novel therapeutics, and diagnosing and monitoring the disease in the clinical setting. However, challenges pertaining to the limited resolution, lack of specificity, inherent technological biases, and processing of increasingly big datasets have hindered comprehensive insights into the pathology underlying disability.Here, we review the advances in neuroimaging for MS that have moved the field forward in recent years by addressing the above-mentioned issues, thereby enhancing our knowledge of this yet enigmatic disease. We discuss complementary imaging technologies, including magnetic resonance imaging, positron emission tomography, and optical coherence tomography, the most recent tool in the MS imaging armamentarium that holds promise to act as a surrogate of pathological changes in the central nervous system in a more easily accessible way.

scholarly journals Neonatal cortical astrocytes possess intrinsic potential in neuronal conversion in defined media

2021 ◽  
Author(s):  
Peng Zeng ◽  
Qiu-hong Hua ◽  
Jun-yuan Gong ◽  
Chang-jie Shi ◽  
Xiao-ping Pi ◽  
...  
Keyword(s):  
Detailed Comparison ◽  
Brain Regions ◽  
Culture Conditions ◽  
Neuronal Markers ◽  
Electrophysiological Properties ◽  
Neuronal Progenitor ◽  
Cortical Astrocytes ◽  
The Central Nervous System ◽  
And Function

AbstractAstrocytes are multifunctional brain cells responsible for maintaining the health and function of the central nervous system. Accumulating evidence suggests that astrocytes might be complementary source across different brain regions to supply new neurons during adult neurogenesis. In this study, we found that neonatal mouse cortical astrocytes can be directly converted into neurons when exposed to neurogenic differentiation culture conditions, with insulin being the most critical component. Detailed comparison studies between mouse cortical astrocytes and neuronal progenitor cells (NPCs) demonstrated the converted neuronal cells originate indeed from the astrocytes rather than NPCs. The neurons derived from mouse cortical astrocytes display typical neuronal morphologies, express neuronal markers and possess typical neuronal electrophysiological properties. More importantly, these neurons can survive and mature in the mouse brain in vivo. Finally, by comparing astrocytes from different brain regions, we found that only cortical astrocytes but not astrocytes from other brain regions such as hippocampus and cerebellum can be converted into neurons under the current condition. Altogether, our findings suggest that neonatal astrocytes from certain brain regions possess intrinsic potential to differentiate/transdifferentiate into neurons which may have clinical relevance in the future.

scholarly journals Voluntary Behavior and Training Conditions Modulate in vivo Extracellular Glucose and Lactate in the Mouse Primary Motor Cortex

2022 ◽  
Vol 15 ◽  
Author(s):  
Alexandria Béland-Millar ◽  
Claude Messier
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Wheel Running ◽  
Aerobic Glycolysis ◽  
Metabolic Cost ◽  
Main Function ◽  
Extracellular Glucose ◽  
Extracellular Lactate ◽  
The Impact

Learning or performing new behaviors requires significant neuronal signaling and is metabolically demanding. The metabolic cost of performing a behavior is mitigated by exposure and practice which result in diminished signaling and metabolic requirements. We examined the impact of novel and habituated wheel running, as well as effortful behaviors on the modulation of extracellular glucose and lactate using biosensors inserted in the primary motor cortex of mice. We found that motor behaviors produce increases in extracellular lactate and decreases in extracellular glucose in the primary motor cortex. These effects were modulated by experience, novelty and intensity of the behavior. The increase in extracellular lactate appears to be strongly associated with novelty of a behavior as well as the difficulty of performing a behavior. Our observations are consistent with the view that a main function of aerobic glycolysis is not to fuel the current neuronal activity but to sustain new bio-infrastructure as learning changes neural networks, chiefly through the shuttling of glucose derived carbons into the pentose phosphate pathway for the biosynthesis of nucleotides.

Electrophysiological characterization of different types of neurons recorded in vivo in the motor cortex of the cat. I. Patterns of firing activity and synaptic responses

1993 ◽  
Vol 69 (6) ◽  
pp. 1850-1864 ◽  
Author(s):  
A. Baranyi ◽  
M. B. Szente ◽  
C. D. Woody
Keyword(s):  
Motor Cortex ◽  
Action Potentials ◽  
Pyramidal Tract ◽  
Class Iii ◽  
Firing Activity ◽  
Electrophysiological Properties ◽  
Antidromic Response ◽  
Stimulation Of ◽  
Synaptic Responses

1. Patterns of firing activity and characteristics of antidromic and synaptic responses to stimulation of the pyramidal tract at peduncular level [peduncular pyramidal tract (PP)] and the ventrolateral thalamic nucleus (VL) were studied in neurons of area 4 gamma of the motor cortex of awake, chronic cats using intracellular microelectrode techniques. The results offer a new functional classification of neocortical neurons based on electrophysiological properties of the 640 recorded cells. 2. Four classes of neurons were distinguished: (class i) inactivating bursting (ib) neurons (n = 60) including fast antidromic response PP (fPP) (n = 0), slow antidromic response PP (sPP) (n = 11), and no antidromic response PP cells (nPP) (n = 49); (class ii) noninactivating bursting (nib) neurons (n = 79), including fPP (n = 23), sPP (n = 0), and nPP cells (n = 56); (class iii) fast-spiking (fsp) neurons (n = 56), including fPP (n = 0), sPP (n = 0), and nPP cells (n = 56); and (class iv) regular-spiking (rsp) neurons (n = 445), including fPP (n = 96), sPP (n = 38), and nPP cells (n = 311). (Neurons in each classification were further separated by their antidromic responses to PP stimulation: fast PP (fPP) slow PP (sPP), or nPP cells, the latter not responding antidromically to electrical stimulation of the peduncle.) 3. Recurrent monosynaptic excitatory postsynaptic potentials (EPSPs) followed antidromic spikes elicited by PP stimulation in most (96%) fPP but much fewer (24%) sPP cells. In fPP cells, it was possible to separate the PP EPSPs into two monosynaptic EPSP components that were generated by other fPP and sPP cells, respectively. VL stimulation evoked monosynaptic EPSPs in 100% of fPP cells (vs. 63% of sPP cells) and antidromic action potentials in 16% of fPP cells (vs. 12% of sPP cells). 4. Firing activity consisted of single spike discharges in most PP cells; however, noninactivating bursting was observed in 19% of fPP cells, and inactivating bursting was observed in 23% of sPP cells (see below). In 18% of ib and 11% of nib/nPP neurons, VL stimulation elicited antidromic action potentials. Other bursting neurons proved to be PP cells with characteristic differences in axonal conduction velocity (see above). All PP cells among the nib cells were fPP, and all PP cells among the ib cells were sPP cells. All fsp neurons were found to be nPP cells, and none could be activated antidromically by VL stimulation. Thus the fsp pattern of discharge distinguished a unique class of nPP cells.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Microglial responses to CSF1 overexpression do not promote the expansion of other glial lineages

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ishani De ◽  
Vilena Maklakova ◽  
Suzanne Litscher ◽  
Michelle M. Boyd ◽  
Lucas C. Klemm ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Adult Mice ◽  
M2 Polarization ◽  
The Central Nervous System ◽  
Immune Related Genes ◽  
Glial Lineage ◽  
The Impact ◽  
Stimulating Factor ◽  
Mitogenic Signal

Abstract Background Colony-stimulating factor 1 (CSF1) expression in the central nervous system (CNS) increases in response to a variety of stimuli, and CSF1 is overexpressed in many CNS diseases. In young adult mice, we previously showed that CSF1 overexpression in the CNS caused the proliferation of IBA1+ microglia without promoting the expression of M2 polarization markers. Methods Immunohistochemical and molecular analyses were performed to further examine the impact of CSF1 overexpression on glia in both young and aged mice. Results As CSF1 overexpressing mice age, IBA1+ cell numbers are constrained by a decline in proliferation rate. Compared to controls, there were no differences in expression of the M2 markers ARG1 and MRC1 (CD206) in CSF1 overexpressing mice of any age, indicating that even prolonged exposure to increased CSF1 does not impact M2 polarization status in vivo. Moreover, RNA-sequencing confirmed the lack of increased expression of markers of M2 polarization in microglia exposed to CSF1 overexpression but did reveal changes in expression of other immune-related genes. Although treatment with inhibitors of the CSF1 receptor, CSF1R, has been shown to impact other glia, no increased expression of oligodendrocyte lineage or astrocyte markers was observed in CSF1 overexpressing mice. Conclusions Our study indicates that microglia are the primary glial lineage impacted by CSF1 overexpression in the CNS and that microglia ultimately adapt to the presence of the CSF1 mitogenic signal.

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