scholarly journals Perspectives of RAS and RHEB GTPase Signaling Pathways in Regenerating Brain Neurons

2018 ◽  
Vol 19 (12) ◽  
pp. 4052 ◽  
Author(s):  
Hendrik Schöneborn ◽  
Fabian Raudzus ◽  
Mathieu Coppey ◽  
Sebastian Neumann ◽  
Rolf Heumann
Keyword(s):  
Substantia Nigra ◽  
Signaling Pathways ◽  
Neuronal Cell ◽  
Axonal Growth ◽  
Brain Regions ◽  
Mitogen Activated Protein Kinase ◽  
Brain Functions ◽  
Neuronal Cell Bodies ◽  
Magnetic Guidance ◽  
Novel Concept

Cellular activation of RAS GTPases into the GTP-binding “ON” state is a key switch for regulating brain functions. Molecular protein structural elements of rat sarcoma (RAS) and RAS homolog protein enriched in brain (RHEB) GTPases involved in this switch are discussed including their subcellular membrane localization for triggering specific signaling pathways resulting in regulation of synaptic connectivity, axonal growth, differentiation, migration, cytoskeletal dynamics, neural protection, and apoptosis. A beneficial role of neuronal H-RAS activity is suggested from cellular and animal models of neurodegenerative diseases. Recent experiments on optogenetic regulation offer insights into the spatiotemporal aspects controlling RAS/mitogen activated protein kinase (MAPK) or phosphoinositide-3 kinase (PI3K) pathways. As optogenetic manipulation of cellular signaling in deep brain regions critically requires penetration of light through large distances of absorbing tissue, we discuss magnetic guidance of re-growing axons as a complementary approach. In Parkinson’s disease, dopaminergic neuronal cell bodies degenerate in the substantia nigra. Current human trials of stem cell-derived dopaminergic neurons must take into account the inability of neuronal axons navigating over a large distance from the grafted site into striatal target regions. Grafting dopaminergic precursor neurons directly into the degenerating substantia nigra is discussed as a novel concept aiming to guide axonal growth by activating GTPase signaling through protein-functionalized intracellular magnetic nanoparticles responding to external magnets.

scholarly journals White Matter Signals Reflect Information Transmission Between Brain Regions During Seizures

2021 ◽  
Author(s):  
Andrew Y. Revell ◽  
Alexander B. Silva ◽  
Dhanya Mahesh ◽  
Lena Armstrong ◽  
T. Campbell Arnold ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Function ◽  
Neuronal Cell ◽  
Brain Regions ◽  
Blood Oxygenation ◽  
Intracranial Eeg ◽  
Brain Functions ◽  
Neuronal Cell Bodies ◽  
Neural Communication ◽  
Oxygenation Level

White matter supports critical brain functions such as learning and memory, modulates the distribution of action potentials, and acts as a relay of neural communication between different brain regions. Interestingly, neuronal cell bodies exist in deeper white matter tissue, neurotransmitter vesicles are released directly in white matter, and white matter blood-oxygenation level dependent (BOLD) signals are detectable across a range of different tasks -- all appearing to reflect intrinsic electrical signals in white matter. Yet, such signals within white matter have largely been ignored. Here, we elucidate the properties of white matter signals using intracranial EEG. We show that such signals capture the communication between brain regions and differentiate pathophysiologies of epilepsy. In direct contradiction to past assumptions about white matter inactivity, we show that white matter recordings can elucidate brain function and pathophysiology not apparent in gray matter. Broadly, white matter functional recordings acquired through implantable devices may provide a wealth of currently untapped knowledge about the neurobiology of disease.

scholarly journals Transplantation of Fetal CNS Tissue Into the Peripheral Nervous System: A Model to Study Aberrant Changes in the Neuronal Cytoskeleton

1991 ◽  
Vol 2 (3-4) ◽  
pp. 193-205 ◽  
Author(s):  
Laurie C. Doering
Keyword(s):  
Nervous System ◽  
Substantia Nigra ◽  
Peripheral Nervous System ◽  
Growth Factor Receptor ◽  
Morphological Characteristics ◽  
Neuronal Cell ◽  
Cytoskeletal Proteins ◽  
Adult Rats ◽  
Neuronal Cell Bodies ◽  
Immunocytochemical Techniques

Defined regions (septum, substantia nigra) of the embryonic central nervous system (CNS) were transplanted into the sciatic nerves of young adult rats. Immunocytochemical techniques were used to examine the expression of neurotransmitter related enzymes and neuronal cytoskeletal proteins in the grafts.The origin of the septal grafts was confirmed by immunoreactivity in nenrons to choline acetyltransferase and the β-nerve growth factor receptor (192-IgG). In substantia nigra grafts, neuronal perikarya and processes were identified with an antibody directed against tyrosine hydroxylase. Typical spatial distributions of phosphorylated (Mr200,000) and non phosphorylated (Mr168,000 & 200,000) neurofilaments were observed in the short term (1-2 months) grafts with the monoclonal antibodies RT97 and SMI-32 respectively. Dense dendrite arbors and neuronal cell bodies were immunostained with an antibody that recognizes a high molecular weight microtubule associated protein (MAP2).In the long term (1 year) transplants, prominent cytoskeletal changes in the somata, axons and dendrites of neurons were evident. The cells showed a shift in phosphorylated neurofilament staining from the axon to the soma accompanied by a reduction in axonal immunoreactivity in the adjacent neuropil, Other abnormal features included swollen perikarya, hypertrophied axonal segments and Short segments of kinked axons. Regression of the dendrite trees in the long standing grafts was also apparent when sections were reacted with the MAP2 antibody.These experiments indicate that grafted fetal neurons, isolated in the peripheral nervous system, differentiate and express markers like their counterpartsin situ. After extended time periods under these circumstances, cytoskeletal modifications become apparent in the neurons. These aberrant changes are similar to morphological characteristics associated with aging and neurodegenerative disorders. This experimental paradigm offers a new approach, to study cytoskeletal disturbances in neurons and provides a unique opportunity to examine conditions that may modulate the abnormal changes.

scholarly journals The potential role of neuroinflammation and transcription factors in Parkinson disease

2017 ◽  
Vol 19 (1) ◽  
pp. 71-80 ◽  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Signaling Pathways ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Brain Regions ◽  
Death Domain

Parkinson disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons affected by inflammatory processes. Post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines, confirming an ongoing neuroinflammation in the affected brain regions. These inflammatory mediators may activate transcription factors—notably nuclear factor κB, Ying-Yang 1 (YY1), fibroblast growth factor 20 (FGF20), and mammalian target of rapamycin (mTOR)—which then regulate downstream signaling pathways that in turn promote death of dopaminergic neurons through death domain-containing receptors. Dopaminergic neurons are vulnerable to oxidative stress and inflammatory attack. An increased level of inducible nitric oxide synthase observed in the substantia nigra and striatum of PD patients suggests that both cytokine—and chemokine-induced toxicity and inflammation lead to oxidative stress that contributes to degeneration of dopaminergic neurons and to disease progression. Lipopolysaccharide activation of microglia in the proximity of dopaminergic neurons in the substantia nigra causes their degeneration, and this appears to be a selective vulnerability of dopaminergic neurons to inflammation. In this review, we will look at the role of various transcription factors and signaling pathways in the development of PD.

scholarly journals Ischemic Cerebral Endothelial Cell–Derived Exosomes Promote Axonal Growth

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3701-3712
Author(s):  
Yi Zhang ◽  
Yi Qin ◽  
Michael Chopp ◽  
Chao Li ◽  
Amy Kemper ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Cell ◽  
Axonal Growth ◽  
Mature Mirnas ◽  
Bioinformatic Analysis ◽  
Axonal Outgrowth ◽  
Ischemic Brain ◽  
Neuronal Homeostasis ◽  
Neuronal Cell Bodies

Background and Purpose: Cerebral endothelial cells (CECs) and axons of neurons interact to maintain vascular and neuronal homeostasis and axonal remodeling in normal and ischemic brain, respectively. However, the role of exosomes in the interaction of CECs and axons in brain under normal conditions and after stroke is unknown. Methods: Exosomes were isolated from CECs of nonischemic rats and is chemic rats (nCEC-exos and isCEC-exos), respectively. A multicompartmental cell culture system was used to separate axons from neuronal cell bodies. Results: Axonal application of nCEC-exos promotes axonal growth of cortical neurons, whereas isCEC-exos further enhance axonal growth than nCEC-exos. Ultrastructural analysis revealed that CEC-exos applied into distal axons were internalized by axons and reached to their parent somata. Bioinformatic analysis revealed that both nCEC-exos and isCEC-exos contain abundant mature miRNAs; however, isCEC-exos exhibit more robust elevation of select miRNAs than nCEC-exos. Mechanistically, axonal application of nCEC-exos and isCEC-exos significantly elevated miRNAs and reduced proteins in distal axons and their parent somata that are involved in inhibiting axonal outgrowth. Blockage of axonal transport suppressed isCEC-exo–altered miRNAs and proteins in somata but not in distal axons. Conclusions: nCEC-exos and isCEC-exos facilitate axonal growth by altering miRNAs and their target protein profiles in recipient neurons.

scholarly journals Developmentally and spatially regulated expression of HNK-1 carbohydrate antigen on a novel phosphatidylinositol-anchored glycoprotein in rat brain.

1991 ◽  
Vol 115 (3) ◽  
pp. 731-744 ◽  
Author(s):  
Y Yoshihara ◽  
S Oka ◽  
Y Watanabe ◽  
K Mori
Keyword(s):  
Cell Surface ◽  
Developmental Stage ◽  
Rat Brain ◽  
Neuronal Cell ◽  
Brain Regions ◽  
Carbohydrate Antigen ◽  
Postnatal Life ◽  
Strongly Coupled ◽  
Brain Membranes ◽  
Neuronal Cell Bodies

HNK-1 carbohydrate antigen in an epitope expressed commonly in many cell surface adhesion and recognition molecules in the nervous system. We purified and characterized from rat brain a novel phosphatidylinositol (PI)-anchored 150-kD glycoprotein belonging to the HNK-1 family. The molecule (PI-GP150) was detected by combination of PI-specific phospholipase C treatment of brain membranes and Western blot analysis with mAb HNK-1. HNK-1-positive PI-GP150 was purified from the PI-PLC-released materials with three successive chromatographies (Sephacryl S-300, mAb HNK-1-Sepharose 4B, and Mono Q) and proven to be a novel molecule by immunoblot and structural analyses. Polyclonal antibody was raised against PI-GP150 and used to show that (a) PI-GP150 is expressed on the surface of neuronal cell bodies and their processes in culture, and (b) PI-GP150 appears during embryonic development and is present throughout all postnatal life in all brain regions. However, the expression of the HNK-1 epitope on PI-GP150 is regulated in both developmental stage-specific and region-specific manners. In newborn rats, the HNK-1 epitope is expressed on PI-GP150 throughout the brain. The level of HNK-1 epitope on PI-GP150 decreases after postnatal day 7 in hindbrain and becomes completely absent in adult myelencephalon and metencephalon. In contrast, HNK-1 epitope on PI-GP150 was constitutively expressed in telencephalon. Thus, while the HNK-1 carbohydrate epitope is strongly coupled to PI-GP150, its expression can be regulated independently of that of PI-GP150. The differential expression of the HNK-1 epitope at different rostro-caudal axial levels was observed also in other HNK-1 family molecules in brain membranes. These results suggest that the HNK-1 epitope plays an important role in adding region-specific and developmental stage-specific modifications on the function of the cell surface molecules.

p42 mitogen-activated protein kinase in brain: Prominent localization in neuronal cell bodies and dendrites

Neuroscience ◽  
1993 ◽  
Vol 55 (2) ◽  
pp. 463-472 ◽  
Author(s):  
R.S. Fiore ◽  
V.E. Bayer ◽  
S.L. Pelech ◽  
J. Posada ◽  
J.A. Cooper ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Neuronal Cell ◽  
Mitogen Activated Protein Kinase ◽  
Neuronal Cell Bodies ◽  
Mitogen Activated Protein

scholarly journals Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models

2008 ◽  
Vol 33 (2) ◽  
pp. 170-179 ◽  
Author(s):  
Camille Brochier ◽  
Marie-Claude Gaillard ◽  
Elsa Diguet ◽  
Nicolas Caudy ◽  
Carole Dossat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Human Brain ◽  
Mouse Brain ◽  
Wild Type Mouse ◽  
Brain Regions ◽  
Expression Data ◽  
Brain Functions

Using serial analysis of gene expression, we collected quantitative transcriptome data in 11 regions of the adult wild-type mouse brain: the orbital, prelimbic, cingulate, motor, somatosensory, and entorhinal cortices, the caudate-putamen, the nucleus accumbens, the thalamus, the substantia nigra, and the ventral tegmental area. With >1.2 million cDNA tags sequenced, this database is a powerful resource to explore brain functions and disorders. As an illustration, we performed interregional comparisons and found 315 differential transcripts. Most of them are poorly characterized and 20% lack functional annotation. For 78 differential transcripts, we provide independent expression level measurements in mouse brain regions by real-time quantitative RT-PCR. We also show examples where we used in situ hybridization to achieve infrastructural resolution. For 30 transcripts, we next demonstrated that regional enrichment is conserved in the human brain. We then quantified the expression levels of region-enriched transcripts in the R6/2 mouse model of Huntington disease and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease and observed significant alterations in the striatum, cerebral cortex, thalamus and substantia nigra of R6/2 mice and in the striatum of MPTP-treated mice. These results show that the gene expression data provided here for the mouse brain can be used to explore pathophysiological models and disclose transcripts differentially expressed in human brain regions.

The Red Neuronal Pigment in the Nervous System of the Mussel, Mytilus Edulis: Localization and Its Effect on Lateral Ciliary Activity with Spectral and Analytical Changes

1981 ◽  
Vol 39 ◽  
pp. 494-495
Author(s):  
Anthony A. Paparo ◽  
Judith A. Murphy
Keyword(s):  
Nervous System ◽  
Mytilus Edulis ◽  
Neuronal Cell ◽  
Ciliary Activity ◽  
Neuronal Cell Bodies ◽  
The Central Nervous System ◽  
Intracellular Organelles ◽  
The Common ◽  
The Individual ◽  
Cryostat Sections

The purpose of this study was to localize the red neuronal pigment in Mytilus edulis and examine its role in the control of lateral ciliary activity in the gill. The visceral ganglia (Vg) in the central nervous system show an over al red pigmentation. Most red pigments examined in squash preps and cryostat sec tions were localized in the neuronal cell bodies and proximal axon regions. Unstained cryostat sections showed highly localized patches of this pigment scattered throughout the cells in the form of dense granular masses about 5-7 um in diameter, with the individual granules ranging from 0.6-1.3 um in diame ter. Tissue stained with Gomori's method for Fe showed bright blue granular masses of about the same size and structure as previously seen in unstained cryostat sections.Thick section microanalysis (Fig.l) confirmed both the localization and presence of Fe in the nerve cell. These nerve cells of the Vg share with other pigmented photosensitive cells the common cytostructural feature of localization of absorbing molecules in intracellular organelles where they are tightly ordered in fine substructures.

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