Prosaposin and its receptors GRP37 and GPR37L1 show increased immunoreactivity in the facial nucleus following facial nerve transection

Neurotrophic factor prosaposin (PS) is a precursor for saposins A, B, C, and D, which are activators for specific sphingolipid hydrolases in lysosomes. Both saposins and PS are widely contained in various tissues. The brain, skeletal muscle, and heart cells predominantly contain unprocessed PS rather than saposins. PS and PS-derived peptides stimulate neuritogenesis and increase choline acetyltransferase activity in neuroblastoma cells and prevent programmed cell death in neurons. We previously detected increases in PS immunoactivity and its mRNA in the rat facial nucleus following facial nerve transection. PS mRNA expression increased not only in facial motoneurons, but also in microglia during facial nerve regeneration. In the present study, we examined the changes in immunoreactivity of the PS receptors GPR37 and GPR37L1 in the rat facial nucleus following facial nerve transection. Following facial nerve transection, many small Iba1- and glial fibrillary acidic protein (GFAP)-positive cells with strong GPR37L1 immunoreactivity, including microglia and astrocytes, were observed predominately on the operated side. These results indicate that GPR37 mainly works in neurons, whereas GPR37L1 is predominant in microglia or astrocytes, and suggest that increased PS in damaged neurons stimulates microglia or astrocytes via PS receptor GPR37L1 to produce neurotrophic factors for neuronal recovery.

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Facial Nerve Transection Causes Expansion of Myelin Autoreactive T Cells in Regional Lymph Nodes and T Cell Homing to the Facial Nucleus

Autoimmunity ◽

10.3109/08916939209001912 ◽

1992 ◽

Vol 13 (2) ◽

pp. 117-126 ◽

Cited By ~ 63

Author(s):

Tomas Olsson ◽

Per Diener ◽

Åke Ljungdahl ◽

Bo Höjeberg ◽

Peter H. Van Der Meide ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Facial Nerve ◽

Lymph Nodes ◽

Nerve Transection ◽

Facial Nucleus ◽

Regional Lymph Nodes ◽

Autoreactive T Cells ◽

Cell Homing ◽

T Cell Homing

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Molecular and Functional Interaction of the Myokine Irisin with Physical Exercise and Alzheimer’s Disease

Molecules ◽

10.3390/molecules23123229 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3229 ◽

Cited By ~ 7

Author(s):

Yunho Jin ◽

Dewan Sumsuzzman ◽

Jeonghyun Choi ◽

Hyunbon Kang ◽

Sang-Rae Lee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Skeletal Muscle ◽

Alzheimer's Disease ◽

Physical Exercise ◽

Beneficial Effect ◽

Neurotrophic Factors ◽

Potential Role ◽

Functional Interaction ◽

Aβ Aggregation ◽

The Brain

Irisin, a skeletal muscle-secreted myokine, produced in response to physical exercise, has protective functions in both the central and the peripheral nervous systems, including the regulation of brain-derived neurotrophic factors. In particular, irisin is capable of protecting hippocampus. Since this area is the region of the brain that is most susceptible to Alzheimer’s disease (AD), such beneficial effect may inhibit or delay the emergence of neurodegenerative diseases, including AD. Also, the factors engaged in irisin formation appear to suppress Aβ aggregation, which is the pathological hallmark of AD. This review is based on the hypothesis that irisin produced by physical exercise helps to control AD progression. Herein, we describe the physiology of irisin and its potential role in delaying or preventing AD progression in human.

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Expression of tPA mRNA in the facial nucleus following facial nerve transection in the rat

Neuroreport ◽

10.1097/00001756-199701200-00008 ◽

1997 ◽

Vol 8 (2) ◽

pp. 419-422 ◽

Cited By ~ 4

Author(s):

Takamichi Yuguchi ◽

Eiji Kohmura ◽

Kazuo Yamada ◽

Hideo Otsuki ◽

Takayuki Sakaki ◽

...

Keyword(s):

Facial Nerve ◽

Nerve Transection ◽

Facial Nucleus

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Motor neuronal and glial apoptosis in the adult facial nucleus after intracranial nerve transection

Journal of Neurosurgery ◽

10.3171/jns.2006.104.3.411 ◽

2006 ◽

Vol 104 (3) ◽

pp. 411-418 ◽

Cited By ~ 8

Author(s):

Per Mattsson ◽

Kioumars Delfani ◽

Ann Marie Janson ◽

Mikael Svensson

Keyword(s):

Facial Nerve ◽

Motor Neurons ◽

Neuronal Apoptosis ◽

Neuronal Loss ◽

Terminal Deoxynucleotidyl Transferase ◽

Cresyl Violet ◽

Nerve Transection ◽

Facial Nucleus ◽

Double Labeling ◽

Intracranial Lesions

Object Intracranial lesions affecting the facial nerve are usually associated with significant morbidity and poor functional restitution, despite the fact that a peripheral nerve injury normally recovers well. Mechanistic explanations are needed to direct future therapies. Although neonatal motor neurons are known to die as a result of apoptosis after axotomy, this cell death mechanism has not been explicitly demonstrated after peripheral cranial nerve transection in adult mammals. Methods The authors induced substantial retrograde neuronal death in the adult rodent by transecting the facial nerve during its intracranial course. Neuronal apoptosis was demonstrated as shrunken facial motor neurons, retrogradely labeled with fluorogold and with nuclei positively labeled by terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick–end labeling (TUNEL). Glial apoptosis was demonstrated by double labeling with respect to cell type. On postinjury Days 7 and 14, the intracranial axotomy led to neuronal apoptosis, corresponding to a neuronal loss that was observed quantitatively in cresyl violet–stained tissue sections obtained using a stereological method. In contrast, no neuronal apoptosis was observed after creating a distal lesion of the facial nerve, which causes less neuronal loss. In addition, glial apoptosis was seen in the facial nucleus after both distal and proximal axotomy. Whereas the proximal intracranial axotomy led to TUNEL-positive nuclei in cells showing markers for oligodendrocytes and microglia, only the latter glial cell population was double labeled with TUNEL-positive nuclei after distal lesioning. Conclusions These findings may ultimately lead to new therapeutic strategies in patients suffering from facial nerve palsy due to an intracranial lesion.

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Neuropeptides Involved in Facial Nerve Regeneration

Biomedicines ◽

10.3390/biomedicines9111575 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1575

Author(s):

Inhyeok Kim ◽

Yonjae Kim ◽

Daewoong Kang ◽

Junyang Jung ◽

Sungsoo Kim ◽

...

Keyword(s):

Facial Nerve ◽

Adenylyl Cyclase ◽

Nerve Regeneration ◽

Neurotrophic Factors ◽

Animal Studies ◽

Nerve Damage ◽

Neural Regeneration ◽

Nerve Degeneration ◽

Calcitonin Gene ◽

Facial Motoneurons

Neuropeptides and neurotransmitters act as intermediaries to transmit impulses from one neuron to another via a synapse. These neuropeptides are also related to nerve degeneration and regeneration during nerve damage. Although there are various neuropeptides, three are associated with neural regeneration in facial nerve damage: calcitonin gene-related peptide (CGRP), galanin, and pituitary adenylyl cyclase-activating peptide (PACAP). Alpha CGRP in facial motoneurons is a signaling factor involved in neuroglial and neuromuscular interactions during regeneration. Thus, it may be a marker for facial nerve regeneration. Galanin is a marker of injured axons rather than nerve regeneration. PACAP has various effects on nerve regeneration by regulating the surrounding cells and providing neurotrophic factors. Thus, it may also be used as a marker for facial nerve regeneration. However, the precise roles of these substances in nerve generation are not yet fully understood. Animal studies have demonstrated that they may act as neuromodulators to promote neurotrophic factors involved in nerve regeneration as they appear early, before changes in the injured cells and their environment. Therefore, they may be markers of nerve regeneration.

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Endotoxin Alteration of the Mucopolysaccharide Blood Vessel Coating in Rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100050755 ◽

1974 ◽

Vol 32 ◽

pp. 148-149

Author(s):

D. E. Philpott ◽

A. Takahashi

Keyword(s):

Skeletal Muscle ◽

Endothelial Cells ◽

Salivary Gland ◽

Carotid Artery ◽

Basement Membrane ◽

Coronary Vessels ◽

Ruthenium Red ◽

E Coli ◽

Old Rats ◽

The Brain

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.

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UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation

Nature Communications ◽

10.1038/s41467-021-23597-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Manivannan Subramanian ◽

Seung Jae Hyeon ◽

Tanuza Das ◽

Yoon Seok Suh ◽

Yun Kyung Kim ◽

...

Keyword(s):

Mouse Model ◽

Ubiquitin Ligase ◽

Therapeutic Approach ◽

Target Gene ◽

Neuroblastoma Cells ◽

E3 Ligase ◽

Tau Hyperphosphorylation ◽

Phosphorylated Tau ◽

Major Pathway ◽

The Brain

AbstractThe formation of hyperphosphorylated intracellular Tau tangles in the brain is a hallmark of Alzheimer’s disease (AD). Tau hyperphosphorylation destabilizes microtubules, promoting neurodegeneration in AD patients. To identify suppressors of tau-mediated AD, we perform a screen using a microRNA (miR) library in Drosophila and identify the miR-9 family as suppressors of human tau overexpression phenotypes. CG11070, a miR-9a target gene, and its mammalian orthologue UBE4B, an E3/E4 ubiquitin ligase, alleviate eye neurodegeneration, synaptic bouton defects, and crawling phenotypes in Drosophila human tau overexpression models. Total and phosphorylated Tau levels also decrease upon CG11070 or UBE4B overexpression. In mammalian neuroblastoma cells, overexpression of UBE4B and STUB1, which encodes the E3 ligase CHIP, increases the ubiquitination and degradation of Tau. In the Tau-BiFC mouse model, UBE4B and STUB1 overexpression also increase oligomeric Tau degradation. Inhibitor assays of the autophagy and proteasome systems reveal that the autophagy-lysosome system is the major pathway for Tau degradation in this context. These results demonstrate that UBE4B, a miR-9 target gene, promotes autophagy-mediated Tau degradation together with STUB1, and is thus an innovative therapeutic approach for AD.

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Lack of Skeletal Muscle Serotonin Impairs Physical Performance

International Journal of Tryptophan Research ◽

10.1177/11786469211003109 ◽

2021 ◽

Vol 14 ◽

pp. 117864692110031

Author(s):

Marion Falabrègue ◽

Anne-Claire Boschat ◽

Romain Jouffroy ◽

Marieke Derquennes ◽

Haidar Djemai ◽

...

Keyword(s):

Skeletal Muscle ◽

Endurance Training ◽

Physical Performance ◽

Depressive Disorders ◽

Tryptophan Metabolism ◽

Long Distance ◽

Positive Effects ◽

Tryptophan Metabolites ◽

The Brain ◽

Deficient Mice

Low levels of the neurotransmitter serotonin have been associated with the onset of depression. While traditional treatments include antidepressants, physical exercise has emerged as an alternative for patients with depressive disorders. Yet there remains the fundamental question of how exercise is sensed by the brain. The existence of a muscle–brain endocrine loop has been proposed: according to this scenario, exercise modulates metabolization of tryptophan into kynurenine within skeletal muscle, which in turn affects the brain, enhancing resistance to depression. But the breakdown of tryptophan into kynurenine during exercise may also alter serotonin synthesis and help limit depression. In this study, we investigated whether peripheral serotonin might play a role in muscle–brain communication permitting adaptation for endurance training. We first quantified tryptophan metabolites in the blood of 4 trained athletes before and after a long-distance trail race and correlated changes in tryptophan metabolism with physical performance. In parallel, to assess exercise capacity and endurance in trained control and peripheral serotonin–deficient mice, we used a treadmill incremental test. Peripheral serotonin–deficient mice exhibited a significant drop in physical performance despite endurance training. Brain levels of tryptophan metabolites were similar in wild-type and peripheral serotonin–deficient animals, and no products of muscle-induced tryptophan metabolism were found in the plasma or brains of peripheral serotonin–deficient mice. But mass spectrometric analyses revealed a significant decrease in levels of 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in both the soleus and plantaris muscles, demonstrating that metabolization of tryptophan into serotonin in muscles is essential for adaptation to endurance training. In light of these findings, the breakdown of tryptophan into peripheral but not brain serotonin appears to be the rate-limiting step for muscle adaptation to endurance training. The data suggest that there is a peripheral mechanism responsible for the positive effects of exercise, and that muscles are secretory organs with autocrine-paracrine roles in which serotonin has a local effect.

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