scholarly journals Autophagy in Neurotrauma: Good, Bad, or Dysregulated

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 693 ◽  
Author(s):  
Junfang Wu ◽  
Marta M. Lipinski
Keyword(s):  
Spinal Cord ◽  
Membrane Damage ◽  
Strong Support ◽  
Experimental Models ◽  
Autophagic Flux ◽  
Central Nervous Systems ◽  
Autophagic Degradation ◽  
Degradation Activity ◽  
Cellular Components

Autophagy is a physiological process that helps maintain a balance between the manufacture of cellular components and breakdown of damaged organelles and other toxic cellular constituents. Changes in autophagic markers are readily detectable in the spinal cord and brain following neurotrauma, including traumatic spinal cord and brain injury (SCI/TBI). However, the role of autophagy in neurotrauma remains less clear. Whether autophagy is good or bad is under debate, with strong support for both a beneficial and detrimental role for autophagy in experimental models of neurotrauma. Emerging data suggest that autophagic flux, a measure of autophagic degradation activity, is impaired in injured central nervous systems (CNS), and interventions that stimulate autophagic flux may provide neuroprotection in SCI/TBI models. Recent data demonstrating that neurotrauma can cause lysosomal membrane damage resulting in pathological autophagosome accumulation in the spinal cord and brain further supports the idea that the impairment of the autophagy–lysosome pathway may be a part of secondary injury processes of SCI/TBI. Here, we review experimental work on the complex and varied responses of autophagy in terms of both the beneficial and detrimental effects in SCI and TBI models. We also discuss the existing and developing therapeutic options aimed at reducing the disruption of autophagy to protect the CNS after injuries.

scholarly journals Simvastatin accelerated motoneurons death in SOD1G93A mice through inhibiting Rab7-mediated maturation of late autophagic vacuoles

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Lin Bai ◽  
Yafei Wang ◽  
Jia Huo ◽  
Shuai Li ◽  
Ya Wen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Autophagic Flux ◽  
Disease Phenotype ◽  
Simvastatin Treatment ◽  
Previous Evidence ◽  
Ischemic Diseases ◽  
Coa Reductase ◽  
Cancer And Inflammation ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by motoneuron loss, for which there is currently no effective treatment. Statins, as inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, are used as drugs for treatment for a variety of disease such as ischemic diseases, neurodegenerative diseases, cancer, and inflammation. However, our previous evidence has demonstrated that simvastatin leads to cytotoxicity in NSC34-hSOD1G93A cells by aggravating the impairment of autophagic flux, but the role of simvastatin in ALS model remains elusive. In present study, we reported that after simvastatin treatment, SOD1G93A mice showed early onset of the disease phenotype and shortened life span, with aggravated autophagic flux impairment and increased aggregation of SOD1 protein in spinal cord motoneurons (MNs) of SOD1G93A mice. In addition, simvastatin repressed the ability of Rab7 localization on the membrane by inhibiting isoprenoid synthesis, leading to impaired late stage of autophagic flux rather than initiation. This study suggested that simvastatin significantly worsened impairment of late autophagic flux, resulting in massive MNs death in spinal cord and accelerated disease progression of SOD1G93A mice. Together, these findings might imply a potential risk of clinic application of statins in ALS.

scholarly journals SGK1 Inhibits Autophagy in Murine Muscle Tissue

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Theresia Zuleger ◽  
Julia Heinzelbecker ◽  
Zsuzsanna Takacs ◽  
Catherine Hunter ◽  
Jakob Voelkl ◽  
...  
Keyword(s):  
Muscle Tissue ◽  
White Muscle ◽  
Autophagic Flux ◽  
Tissue Extracts ◽  
Muscle Tissues ◽  
Red Muscle ◽  
Autophagic Degradation

Background/Aims. As autophagy is linked to several pathological conditions, like cancer and neurodegenerative diseases, it is crucial to understand its regulatory signaling network. In this study, we investigated the role of the serum- and glucocorticoid-induced protein kinase 1 (SGK1) in the control of autophagy. Methods. To measure autophagic activity in vivo, we quantified the abundance of the autophagy conjugates LC3-PE (phosphatidylethanolamine) and ATG12-ATG5 in tissue extracts of SGK1 wild-type (Sgk1+/+) and knockout (Sgk1−/−) mice that were either fed or starved for 24 h prior sacrifice. In vitro, we targeted SGK1 by RNAi using GFP-WIPI1 expressing U-2 OS cells to quantify the numbers of cells displaying newly formed autophagosomes. In parallel, these cells were also assessed with regard to LC3 and ULK1 by quantitative Western blotting. Results. The abundance of both LC3-PE (LC3-II) and ATG12-ATG5 was significantly increased in red muscle tissues of SGK1 knockout mice. This was found in particular in fed conditions, suggesting that SGK1 may keep basal autophagy under control in red muscle in vivo. Under starved conditions, significant differences were observed in SGK1-deficient white muscle tissue and, under fed conditions, also in the liver. In vitro, we found that SGK1 silencing provoked a significant increase of cells displaying WIPI1-positive autophagosomes and autophagosomal LC3 (LC3-II). Moreover, autophagic flux assessments revealed that autophagic degradation significantly increased in the absence of SGK1, strongly suggesting that SGK1 inhibits both autophagosome formation and autophagic degradation in vitro. In addition, more ULK1 protein lacking the inhibitory, TORC1-specific phosphorylation at serine 758 was detected in the absence of SGK1. Conclusions. Combined, our data strongly support the idea that SGK1 inhibits the process of autophagy. Mechanistically, our data suggest that SGK1 should act upstream of ULK1 in regulating autophagy, and we hypothesize that SGK1 contributes to the regulation of ULK1 gene expression.

scholarly journals Spinal cord microglia in health and disease

Acta Naturae ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 4-17
Author(s):  
Elena Kolos ◽  
Dmitry Korzhevsky
Keyword(s):  
Spinal Cord ◽  
Experimental Studies ◽  
Experimental Models ◽  
Specific Marker ◽  
Marker Proteins ◽  
Health And Disease ◽  
And Function ◽  
Lateral Sclerosis

The review summarizes data of recent experimental studies on spinal microglia, the least explored cells of the spinal cord. It focuses on the origin and function of microglia in mammalian spinal cord embryogenesis. The main approaches to the classification of microgliocytes based on their structure, function, and immunophenotypic characteristics are analyzed. We discuss the results of studies conducted on experimental models of spinal cord diseases such as multiple sclerosis, amyotrophic lateral sclerosis, systemic inflammation, and some others, with special emphasis on the key role of microglia in the pathogenesis of these diseases. The review highlights the need to detect the new microglia-specific marker proteins expressed at all stages of ontogeny. New sensitive and selective microglial markers are necessary in order to improve identification of spinal cord microgliocytes in normal and pathological conditions. Possible morphometric methods to assess the functional activity of microglial cells are presented.

Acute spinal cord injury in rats should target activated autophagy

2014 ◽  
Vol 20 (5) ◽  
pp. 568-577 ◽  
Author(s):  
Hongping Hou ◽  
Lihai Zhang ◽  
Licheng Zhang ◽  
Peifu Tang
Keyword(s):  
Electron Microscopy ◽  
Spinal Cord ◽  
Caspase 3 ◽  
Potential Role ◽  
Autophagic Flux ◽  
Autophagosome Formation ◽  
Expression Levels ◽  
Cord Injury ◽  
Microscopy Images

Object Autophagy is a cellular mechanism of maintaining balance between protein synthesis and degradation; the latter can be induced by starvation and neurodegenerative disease. Spinal cord injury (SCI) induces necrosis and apoptosis. Autophagic flux has not yet been defined, especially the potential role of autophagy in relation to apoptosis in different tissue cells. The object of this study was to investigate the occurrence of autophagic flux and the potential role of autophagy and apoptosis post-SCI in rats. Methods Following creation of SCI in rats, activation of autophagic flux was detected at the protein (LC3, beclin1, and p62) and mRNA (beclin1) levels and on electron microscopy images. Distribution of LC3, colocalization of activated caspase-3, and changes in expression levels of bcl-2 and Bax were assessed to investigate the potential role of autophagy and apoptosis. Sprague-Dawley rats were used, and T9–10 hemitransection was performed. Expression levels of LC3, beclin1, p62, bcl-2, and Bax were assessed by Western blot analysis, and beclin1 mRNA levels were assessed by reverse transcription–polymerase chain reaction. Distribution of LC3 and colocalization of activated caspase-3 were analyzed by immunohistochemistry. Autophagosome formation was investigated by electron microscopy. Results The authors found a dramatic elevation in LC3 and beclin1 levels near the scar region. Using double staining, they observed that upregulation of LC3 started at 4 hours in neurons and at 3 days in astrocytes after SCI. Confocal images indicated that the percentage of neurons with apoptosis was reduced, while the percentage of astrocytes with apoptosis was high at 4 hours, 8 hours, and 1 day post-SCI but decreased sharply at 3 days. Electron microscopy images provided evidence of autophagosome formation. Elimination of p62 indicated occurrence of autophagic flux. Expression levels of bcl-2 and Bax were increased and decreased, respectively, near the injury site. Conclusions The results of this research demonstrated that autophagic flux is activated after SCI. Potentially, inhibition of apoptosis could be a target to promote neural recovery.

A scientific research study on the management of Manyasthamba (Cervical Spondylosis) with Nasya and Nasapana

2019 ◽  
Vol 4 (04) ◽  
Author(s):  
Unnikrishnan V S ◽  
Prashanth A S ◽  
Madhusudan Kulkarni
Keyword(s):  
Spinal Cord ◽  
Clinical Data ◽  
Food Habits ◽  
Cervical Spondylosis ◽  
Research Study ◽  
Weight Bearing ◽  
Scientific Research ◽  
Modern Era ◽  
Treatment Aspect

The science of life Ayurveda, not only deals with the prevention of diseases by maintaining health but also with the alleviation of diseases. In this ultra modern era due to change in lifestyles, sedentary works and food habits, people are unable to follow the Dinacharya and Ritucharya as explained in the classics, which may lead to different diseases. Due to improper postural habits, weight bearing and other unwholesome diets and habits there are higher the chances of discomfort and disease pertaining to spinal cord. Manyasthambha is one such condition that disturbs a big population due to today’s alterations in lifestyle. Here an effort is made to study and understand the role of Nasya Karma, Nasaapana and Shamanaushadhi like Vyoshadi Guggulu in the treatment aspect of this disease. Nasya Karma and Nasaapana provided highly significant results in all the symptoms of Manyasthambha. As per the clinical data, ‘Nasaapana is found to be more effective than Nasya Karma’. So it can be concluded that better results can be obtained with Shaddharana Yoga as Amapachana, Nasaapana with Mashabaladi Kwatha followed by Vyoshadi Guggulu as Shamanoushadhi.

Conceptualizing and Measuring Affective and Cognitive Empathy

2020 ◽  
pp. 8-30
Author(s):  
Ross Buck ◽  
Zhan Xu
Keyword(s):  
Mental States ◽  
Cognitive Empathy ◽  
Emotional Empathy ◽  
Symbolic Communication ◽  
Current State ◽  
Communication Processes ◽  
Neuroscience Research ◽  
Emotion Displays ◽  
Central Nervous Systems

Individual differences in the ability to recognize emotion displays relate strongly to emotional intelligence, and emotional and social competence. However, there is a difference between the ability to judge the emotions of another person (i.e., emotional empathy) and the ability to take the perspective of another person, including making accurate appraisals, attributions, and inferences about the mental states of others (i.e., cognitive empathy). In this chapter, we review the concept of emotional empathy and the current state of the field, including emerging and converging evidence from neuroscience research that emotional and cognitive empathy involve doubly dissociable brain systems. We also discuss emerging literature on the physiological mechanisms underlying empathy in the peripheral and central nervous systems. We then distinguish spontaneous and symbolic communication processes to show how cognitive empathy emerges from emotional empathy during development. Development starts with the prelinguistic mutual contingent responsiveness of infant and caregiver yielding “raw” primary intersubjectivity, then secondary and tertiary intersubjectivity advances with increasing social experience, and finally cognitive empathic abilities expand in perspective taking and Theory of Mind (ToM) skills. We then present an Affect-Reason-Involvement (ARI) model to guide the conceptualization and measurement of emotional and cognitive empathy. We consider emotion correlation scores as a flexible and valid approach to empathy measurement, with implications for understanding the role of discrete emotions in decision making. Finally, we apply this reasoning to recent studies of the role of emotion and empathy in bullying.

Sign in / Sign up

Export Citation Format

Share Document