29,034 results match your criteria glial activation

Mitophagy pathways and Alzheimer's disease: From pathogenesis to treatment.

Mitochondrion 2021 Apr 16. Epub 2021 Apr 16.

Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006. Electronic address:

Alzheimer's disease (AD) is an age-dependent, incurable mental illness that is associated with the accumulation of aggregates of amyloid-beta (Aβ) and hyperphosphorylated tau fragments (p-tau). Detailed studies on postmortem AD brains, cell lines, and mouse models of AD have shown that numerous cellular alterations, including mitochondrial deficits, synaptic disruption and glial/astrocytic activation, are involved in the disease process. Mitophagy is a cellular process by which damaged/weakened mitochondria are selectively eliminated from the cell. Read More

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Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide-induced microglial and astrocytic neuroinflammation by increasing NAD.

J Neurochem 2021 Apr 19. Epub 2021 Apr 19.

Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8640, Japan.

Neuroinflammation is initiated by activation of the brain's innate immune system in response to an inflammatory challenge. Insufficient control of neuroinflammation leads to enhanced or prolonged pathology in various neurological conditions including multiple sclerosis and Alzheimer's disease. Nicotinamide adenine dinucleotide (NAD ) plays critical roles in cellular energy metabolism and calcium homeostasis. Read More

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Adipose-derived stem cells protect motor neurons and reduce glial activation in both and models of ALS.

Mol Ther Methods Clin Dev 2021 Jun 27;21:413-433. Epub 2021 Mar 27.

Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, Faculty of Medicine, Dentistry and Health, The University of Sheffield, 385 Glossop Rd., Sheffield S10 2HQ, UK.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition for which new therapeutic options are urgently needed. We injected GFP adipose-derived stem cells (EGFP-ADSCs) directly into the cerebrospinal fluid (CSF) of transgenic SOD1 mice, a well-characterized model of familial ALS. Despite short-term survival of the injected cells and limited engraftment efficiency, EGFP-ADSCs improved motor function and delayed disease onset by promoting motor neuron (MN) survival and reducing glial activation. Read More

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SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis.

Front Mol Neurosci 2021 31;14:654031. Epub 2021 Mar 31.

Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.

The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of the / genes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. Read More

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Instructive roles of astrocytes in hippocampal synaptic plasticity: neuronal activity-dependent regulatory mechanisms.

FEBS J 2021 Apr 17. Epub 2021 Apr 17.

Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

In the adult hippocampus, synaptic plasticity is important for information processing, learning, and memory encoding. Astrocytes, the most common glial cells, play a pivotal role in the regulation of hippocampal synaptic plasticity. While astrocytes were initially described as a homogenous cell population, emerging evidence indicates that in the adult hippocampus, astrocytes are highly heterogeneous and can differentially respond to changes in neuronal activity in a subregion-dependent manner to actively modulate synaptic plasticity. Read More

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Cerebrospinal Fluid Biomarkers of Myeloid and Glial Cell Activation Are Correlated With Multiple Sclerosis Lesional Inflammatory Activity.

Front Neurosci 2021 30;15:649876. Epub 2021 Mar 30.

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.

Multiple sclerosis (MS)-related inflammation can be divided into lesional activity, mediated by immune cells migrating from the periphery to the central nervous system (CNS) and non-lesional activity, mediated by inflammation compartmentalized to CNS tissue. Lesional inflammatory activity, reflected by contrast-enhancing lesions (CELs) on the magnetic resonance imaging (MRI), is effectively inhibited by current disease modifying therapies (DMTs). While, the effect of DMTs on non-lesional inflammatory activity is currently unknown. Read More

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Naringenin mitigates behavioral alterations and provides neuroprotection against 3-nitropropinoic acid-induced Huntington's disease like symptoms in rats.

Nutr Neurosci 2021 Apr 15:1-11. Epub 2021 Apr 15.

Department of Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India.

Background: Naringenin is a powerful antioxidant and anti-inflammatory flavonoid which has been widely used as a therapeutic agent in various toxic models. However, few studies have clearly discussed the neuromodulatory effects of naringenin against different neurodegenerative disorders.

Aim: We investigated the neuroprotective efficacy of naringenin against 3-nitropropionic acid (3-NP)-induced neurobehavioral, biochemical and histopathological alterations in rats. Read More

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Elevated sTREM2 and NFL levels in patients with sepsis associated encephalopathy.

Int J Neurosci 2021 Apr 14:1-11. Epub 2021 Apr 14.

Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.

Sepsis-associated encephalopathy (SAE) is a common manifestation of sepsis that may lead to cognitive decline. Our aim was to investigate whether the neurofilament light chain (NFL) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) could be utilized as prognostic biomarkers in SAE. In this prospective observational study, baseline serum levels of sTREM2 and cerebrospinal fluid (CSF) levels of sTREM2 and NFL were measured by ELISA in 11 SAE patients and controls. Read More

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Antisense oligonucleotides targeting alternative splicing of Nrcam exon 10 suppress neurite outgrowth of ganglion sensory neurons in vitro.

Neuroreport 2021 May;32(7):548-554

Department of Physiology and Pathophysiology, School of Basic Medical Sciences.

Neuron-glial-related cell adhesion molecule (NrCAM) is a neuronal cell adhesion molecule that has been shown to be involved in several cellular processes in the peripheral nervous system, including neurite outgrowth. We recently reported that alternative splicing of Nrcam mRNA at exon 10 in the dorsal root ganglion (DRG) contributes to the peripheral mechanism of neuropathic pain. Specially, Nrcam antisense oligonucleotides (ASO) targeting Nrcam exon 10, attenuated neuropathic pain hypersensitivities in mice. Read More

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Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice.

J Clin Invest 2021 Apr 13. Epub 2021 Apr 13.

Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States of America.

Synaptic plasticity is identified as innate to hypothalamic feeding circuits in their adaptation to the changing metabolic milieu in control of feeding and obesity. However, less is known about the regulatory principles of the dynamic changes of AgRP perikarya, a crucial region of the neuron gating excitation, and hence, feeding. Here we show that AgRP neurons activated either by food deprivation, ghrelin or chemogenetics decreased their own inhibitory tone while triggering mitochondrial adaptations in neighboring astrocytes. Read More

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Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction.

Behav Brain Res 2021 Apr 15;408:113290. Epub 2021 Apr 15.

Recep Tayyip Erdogan University, Faculty of Medicine, Department of Biochemistry, Rize, Turkey. Electronic address:

It has been established that cisplatin causes neuronal damage and cognitive impairment. However, the mechanism is not sufficiently clear. Apelin-13 is an endogenous peptide with strong neuroprotective effects through the synthesis of neurotrophic factors and suppression of inflammation. Read More

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Chemogenetic manipulation of astrocytic signaling in the basolateral amygdala reduces binge-like alcohol consumption in male mice.

J Neurosci Res 2021 Apr 12. Epub 2021 Apr 12.

Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC, USA.

Binge drinking is a common occurrence in the United States, but a high concentration of alcohol in the blood has been shown to have reinforcing and reciprocal effects on the neuroimmune system in both dependent and non-dependent scenarios. The first part of this study examined alcohol's effects on the astrocytic response in the central amygdala and basolateral amygdala (BLA) in a non-dependent model. C57BL/6J mice were given access to either ethanol, water, or sucrose during a "drinking in the dark" paradigm, and astrocyte number and astrogliosis were measured using immunohistochemistry. Read More

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Inhibitory Smads suppress pancreatic stellate cell activation through negative feedback in chronic pancreatitis.

Ann Transl Med 2021 Mar;9(5):384

Institute of Pancreas, Southeast University, Nanjing, China.

Background: Activation of pancreatic stellate cells (PSCs) is a key cause of chronic pancreatitis (CP), while inhibition of transforming growth factor-β (TGF-β) signaling renders PSCs inactive. Inhibitory Smads (I-Smads) impede TGF-β intracellular signaling and may provide a way to alleviate CP. Thus, we aimed to investigate the molecular mechanism of I-Smads in CP animals and freshly-isolated PSCs. Read More

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Glial Cell-Based Vascular Mechanisms and Transplantation Therapies in Brain Vessel and Neurodegenerative Diseases.

Front Cell Neurosci 2021 26;15:627682. Epub 2021 Mar 26.

Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, United States.

Neurodevelopmental and neurodegenerative diseases (NDDs) with severe neurological/psychiatric symptoms, such as cerebrovascular pathology in AD, CAA, and chronic stroke, have brought greater attention with their incidence and prevalence having markedly increased over the past few years. Causes of the significant neuropathologies, especially those observed in neurological diseases in the CNS, are commonly believed to involve multiple factors such as an age, a total environment, genetics, and an immunity contributing to their progression, neuronal, and vascular injuries. We primarily focused on the studies of glial involvement/dysfunction in part with the blood-brain barrier (BBB) and the neurovascular unit (NVU) changes, and the vascular mechanisms, which have been both suggested as critical roles in chronic stroke and many other NDDs. Read More

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GPR37 modulates progenitor cell dynamics in a mouse model of ischemic stroke.

Exp Neurol 2021 Apr 8:113719. Epub 2021 Apr 8.

Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address:

The generation of neural stem and progenitor cells following injury is critical for the function of the central nervous system, but the molecular mechanisms modulating this response remain largely unknown. We have previously identified the G protein-coupled receptor 37 (GPR37) as a modulator of ischemic damage in a mouse model of stroke. Here we demonstrate that GPR37 functions as a critical negative regulator of progenitor cell dynamics and gliosis following ischemic injury. Read More

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Down-regulation of astrocytic sonic hedgehog by activation of endothelin ET receptors: Involvement in traumatic brain injury-induced disruption of blood brain barrier in a mouse model.

Neurochem Int 2021 Apr 8;146:105042. Epub 2021 Apr 8.

Laboratory of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyama-Kita, Higashinada, Kobe, 668-8558, Japan. Electronic address:

In the adult brain, sonic hedgehog acts on cerebral microvascular endothelial cells to stabilize the blood-brain barrier. The expression of sonic hedgehog by astrocytes is altered during brain injury, and this change has been shown to affect permeability of blood-brain barrier. However, much remains unknown about the regulation of astrocytic sonic hedgehog production. Read More

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OTULIN is a new target of EA treatment in the alleviation of brain injury and glial cell activation via suppression of the NF-κB signalling pathway in acute ischaemic stroke rats.

Mol Med 2021 Apr 9;27(1):37. Epub 2021 Apr 9.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Objective: Ovarian tumour domain deubiquitinase with linear linkage specificity (OTULIN) is a potent negative regulator of the nuclear factor-κB (NF-κB) signalling pathway, and it plays a strong neuroprotective role following acute ischemic stroke. Electroacupuncture (EA) is an effective adjuvant treatment for reducing brain injury and neuroinflammation via the inhibition of NF-κB p65 nuclear translocation, but the underlying mechanism is not clear. The present study investigated whether OTULIN was necessary for EA to mitigate brain injury and glial cell activation in a transient middle cerebral artery occlusion (tMCAO) model in rats. Read More

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Combination of autophagy and NFE2L2/NRF2 activation as a treatment approach for neuropathic pain.

Autophagy 2021 Apr 9:1-21. Epub 2021 Apr 9.

Department of Anesthesiology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.

Macroautophagy/autophagy, an evolutionarily conserved process, plays an important role in the regulation of immune inflammation and nervous system homeostasis. However, the exact role and mechanism of autophagy in pain is still unclear. Here, we showed that impaired autophagy flux mainly occurred in astrocytes during the maintenance of neuropathic pain. Read More

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From "Leaky Gut" to Impaired Glia-Neuron Communication in Depression.

Adv Exp Med Biol 2021 ;1305:129-155

Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

In the last three decades, the robust scientific data emerged, demonstrating that the immune-inflammatory response is a fundamental component of the pathophysiology of major depressive disorder (MDD). Psychological stress and various inflammatory comorbidities contribute to such immune activation. Still, this is not uncommon that patients with depression do not have defined inflammatory comorbidities, and alternative mechanisms of immune activation need to take place. Read More

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Hsp90 co-chaperones, FKBP52 and Aha1, promote tau pathogenesis in aged wild-type mice.

Acta Neuropathol Commun 2021 04 8;9(1):65. Epub 2021 Apr 8.

USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, 33613, USA.

The microtubule associated protein tau is an intrinsically disordered phosphoprotein that accumulates under pathological conditions leading to formation of neurofibrillary tangles, a hallmark of Alzheimer's disease (AD). The mechanisms that initiate the accumulation of phospho-tau aggregates and filamentous deposits are largely unknown. In the past, our work and others' have shown that molecular chaperones play a crucial role in maintaining protein homeostasis and that imbalance in their levels or activity can drive tau pathogenesis. Read More

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Reactive astrocyte-driven epileptogenesis is induced by microglia initially activated following status epilepticus.

JCI Insight 2021 Apr 8. Epub 2021 Apr 8.

Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.

Extensive activation of glial cells during a latent period has been well documented in various animal models of epilepsy. However, it remains unclear whether activated glial cells contribute to epileptogenesis; i.e. Read More

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Systemic administration of a β2-adrenergic receptor agonist reduces mechanical allodynia and suppresses the immune response to surgery in a rat model of persistent post-incisional hypersensitivity.

Mol Pain 2021 Jan-Dec;17:1744806921997206

Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Beta 2 adrenergic receptor (β2 AR) activation in the central and peripheral nervous system has been implicated in nociceptive processing in acute and chronic pain settings with anti-inflammatory and anti-allodynic effects of β2-AR mimetics reported in several pain states. In the current study, we examined the therapeutic efficacy of the β2-AR agonist clenbuterol in a rat model of persistent postsurgical hypersensitivity induced by disruption of descending noradrenergic signaling in rats with plantar incision. We used growth curve modeling of ipsilateral mechanical paw withdrawal thresholds following incision to examine effects of treatment on postoperative trajectories. Read More

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Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Mol Psychiatry 2021 Apr 8. Epub 2021 Apr 8.

Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.

Amyloid-β (Aβ) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aβ produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aβ clearance remain largely unknown. Read More

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The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson's disease.

J Neuroinflammation 2021 Apr 6;18(1):88. Epub 2021 Apr 6.

Department of Cerebral Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Background: It is suggested that neuroinflammation, in which activated microglial cells play a relevant role, contributes to the development of Parkinson's disease (PD). Consequently, the modulation of microglial activation is a potential therapeutic target to be taken into account to act against the dopaminergic neurodegeneration occurring in this neurological disorder. Several soluble and membrane-associated inhibitory mechanisms contribute to maintaining microglial cells in a quiescent/surveillant phenotype in physiological conditions. Read More

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Angiotensin II, ATP and high extracellular potassium induced intracellular calcium responses in primary rat brain endothelial cell cultures.

Cell Biochem Funct 2021 Apr 6. Epub 2021 Apr 6.

Departamento de Medicina y Ciencias de la Salud, Universidad de Sonora, Hermosillo, Sonora, Mexico.

The meninges shield the nervous system from diverse, rather harmful stimuli and pathogens from the periphery. This tissue is composed of brain endothelial cells (BECs) that express diverse ion channels and chemical-transmitter receptors also expressed by neurons and glial cells to communicate with each other. However, information about the effects of ATP and angiotensin II on BECs is scarce, despite their essential roles in blood physiology. Read More

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Mechanisms implicated in the contralateral effect in the central nervous system after unilateral injury: focus on the visual system.

Neural Regen Res 2021 Nov;16(11):2125-2131

Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia and Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIBArrixaca) Murcia, Spain.

The retina, as part of the central nervous system is an ideal model to study the response of neurons to injury and disease and to test new treatments. During the last decade is becoming clear that unilateral lesions in bilateral areas of the central nervous system trigger an inflammatory response in the contralateral uninjured site. This effect has been better studied in the visual system where, as a rule, one retina is used as experimental and the other as control. Read More

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November 2021

HIF-1, the Warburg Effect, and Macrophage/Microglia Polarization Potential Role in COVID-19 Pathogenesis.

Oxid Med Cell Longev 2021 12;2021:8841911. Epub 2021 Mar 12.

Università Magna Grecia, Catanzaro, Italy.

Despite the international scientific community's commitment to improve clinical knowledge about coronavirus disease 2019 (COVID-19), knowledge regarding molecular details remains limited. In this review, we discuss hypoxia's potential role in the pathogenesis of the maladaptive immune reaction against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The state of infection, with serious respiratory dysfunction, causes tissues to become hypoxic due to a discrepancy between cellular O uptake and consumption similar to that seen within tumor tissue during the progression of numerous solid cancers. Read More

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Pulp inflammation induces Kv1.1 K channel down-regulation in rat thalamus.

Oral Dis 2021 Apr 3. Epub 2021 Apr 3.

Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Objectives: Signals from inflamed tooth pulp activate thalamic neurons to evoke central sensitization. We aimed to gain insights into the mechanisms mediating the early phase of pulpal inflammation-induced thalamic neural and glial activation.

Materials And Methods: Pulpal inflammation was induced via the application of mustard oil (MO) to the upper first molar of Wistar rats with local anesthesia (LA) or saline injection. Read More

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Unique metabolic phenotype and its transition during maturation of juvenile male germ cells.

FASEB J 2021 May;35(5):e21513

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.

Human male reproductive development has a prolonged prepubertal period characterized by juvenile quiescence of germ cells with immature spermatogonial stem cell (SSC) precursors (gonocytes) present in the testis for an extended period of time. The metabolism of gonocytes is not defined. We demonstrate with mitochondrial ultrastructure studies via TEM and IHC and metabolic flux studies with UHPLC-MS that a distinct metabolic transition occurs during the maturation to SSCs. Read More

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Amyloid-Beta Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms on Olfactory Ensheathing Cells: Modulatory Effect of Indicaxanthin.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Institute for Biomedical Research and Innovation (IRIB), National Research Council, 95126 Catania, Italy.

Herein, we assessed the effect of full native peptide of amyloid-beta (Aβ) (1-42) and its fragments (25-35 and 35-25) on tissue transglutaminase (TG2) and its isoforms (TG2-Long and TG2-Short) expression levels on olfactory ensheathing cells (OECs). Vimentin and glial fibrillary acid protein (GFAP) were also studied. The effect of the pre-treatment with indicaxanthin from Opuntia ficus-indica fruit on TG2 expression levels and its isoforms, cell viability, total reactive oxygen species (ROS), superoxide anion (O), and apoptotic pathway activation was assessed. Read More

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