Vitamin E induces ramification and downregulation of adhesion molecules in cultured microglial cells

Heppner, Frank L.; Roth, K.; Nitsch, Robert; Hailer, Nils P.

doi:10.1002/(sici)1098-1136(199802)22:2<180::aid-glia9>3.0.co;2-b

Cited by 84 publications

(55 citation statements)

References 49 publications

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“…1s) and week 2 (Fig. 1t), processes of microglia cells within the fimbria appeared to be retracted and cell bodies were swollen, which is frequently associated with microglia activation [10]. Comparable morphological changes of microglia were evident in the CC at weeks 1 and 2.…”

Section: Resultsmentioning

confidence: 99%

The hippocampal fimbria of cuprizone-treated animals as a structure for studying neuroprotection in multiple sclerosis

et al. 2011

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Objective and designIt has been demonstrated that changes in the normal-appearing white matter (NAWM) in multiple sclerosis precede the appearance of classical lesions. The understanding of NAWM biology in an established disease model might help to clarify why some of them progress to active demyelinating lesions.Material or subjectsC57BL6 male mice (19–21 g) were used in this study.TreatmentDemyelination was induced by feeding mice a diet containing 0.2% cuprizone for up to 5 weeks.MethodsRoutine stainings (luxol fast blue, and hematoxylin and eosin) and immunohistochemistry were performed to assess myelin status and the inflammatory infiltrate.ResultsWe demonstrated that, in the toxic demyelination cuprizone model, the corpus callosum is severely demyelinated after a 5-week cuprizone challenge (acute demyelination) whereas the fimbria of the hippocampus appear normal in routine myelin stainings. Microgliosis but not astrogliosis is evident after acute demyelination in the fimbria. Interestingly, both regions, the fimbria and the corpus callosum, demonstrated early oligodendrocyte apoptosis as well as intense microglia accumulation and activation. However, only the corpus callosum progresses to actively demyelination lesions whereas the fimbria does not.ConclusionsThe applied model appears suitable for elucidating pathways which promote progression of affected tissue to an active lesion.

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Section: Resultsmentioning

confidence: 99%

The hippocampal fimbria of cuprizone-treated animals as a structure for studying neuroprotection in multiple sclerosis

et al. 2011

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“…LPL, iNOS and MHC II were analyzed for the percentage of colocalization with Iba1 using Metamorph software. Quantitative evaluation of microglial cell morphology in tissue sections and in vitro was performed as described in the literature using ramification index (RI) calculated by the following equation: 4π × cell area/(cell perimeter) 2 [26]. The RI of perfectly round cells is 1; if morphology deviates from perfectly circular form, RI is smaller than 1; and when the cell is highly ramified the RI is close to zero.…”

Section: Methodsmentioning

confidence: 99%

TREM2 regulates microglial cell activation in response to demyelination in vivo

et al. 2015

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Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2−/−) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2−/− microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2−/− microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in response to tissue damage.

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“…Treatment of cultured microglial cells with the antioxidants vitamin E (alpha-tocopherol) and vitamin C (ascorbic acid) induces a ramified microglial morphology after 48 h in vitro, which only seen in healthy adult CNS tissue or in coculture with astrocytes [78]. Vitamin D hormone (VDH; 1, 25-dihydroxyvitamin D 3 ), the active metabolite of vitamin D, confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons [79].…”

Section: Antioxidant Vitamins (B 3 C D 3 E)mentioning

confidence: 99%

Dual Effects of Antioxidants in Neurodegeneration: Direct Neuroprotection against Oxidative Stress and Indirect Protection via Suppression of Gliamediated Inflammation

Wang¹,

Wen²,

Huang³

et al. 2006

CPD

220

116

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Oxidative stress, in which production of highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) overwhelms antioxidant defenses, is a feature of many neurological diseases and neurodegeneration. ROS and RNS generated extracellularly and intracellularly by various processes initiate and promote neurodegeneration in CNS. ROS and RNS can directly oxidize and damage macromolecules such as DNA, proteins, and lipids, culminating in neurodegeneration in the CNS. Neurons are most susceptible to direct oxidative injury by ROS and RNS. ROS and RNS can also indirectly contribute to tissue damage by activating a number of cellular pathways resulting in the expression of stress-sensitive genes and proteins to cause oxidative injury. Moreover, oxidative stress also activates mechanisms that result in a glia-mediated inflammation that also causes secondary neuronal damage. Associated with neuronal injuries caused by many CNS insults is an activation of glial cells (particularly astrocytes and microglia) at the sites of injury. Activated glial cells are thus histopathological hallmarks of neurodegenerative diseases. Even though direct contact of activated glia with neurons per se may not necessarily be toxic, the immune mediators (e.g. nitric oxide and reactive oxygen species, pro-inflammatory cytokines and chemokines) released by activated glial cells are currently considered to be candidate neurotoxins. Therefore, study of the protective role of antioxidant compounds on inhibition of the inflammatory response and correcting the fundamental oxidant/antioxidant imbalance in patients suffering from neurodegenerative diseases are important vistas for further research. The purpose of this review is to summarize the current evidence in support of this critical role played by oxidative stress of neuronal and glial origin in neurodegenerative diseases. The mechanistic basis of the neuroprotective activity of antioxidants does not only rely on the general free radical trapping or antioxidant activity per se in neurons, but also the suppression of genes induced by pro-inflammatory cytokines and other mediators released by glial cells. We propose that combinations of agents which act at sequential steps in the neurodegenerative process can produce additive neuroprotective effects. A cocktail of multiple antioxidants with anti-inflammatory agents may be more beneficial in the prevention of neurodegenerative disease. A clearer appreciation of the potential therapeutic utility of antioxidants would emerge only when the complexity of their effects on mechanisms that interact to determine the extent of oxidative damage in vivo are more fully defined and understood.

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Vitamin E induces ramification and downregulation of adhesion molecules in cultured microglial cells

Cited by 84 publications

References 49 publications

The hippocampal fimbria of cuprizone-treated animals as a structure for studying neuroprotection in multiple sclerosis

The hippocampal fimbria of cuprizone-treated animals as a structure for studying neuroprotection in multiple sclerosis

TREM2 regulates microglial cell activation in response to demyelination in vivo

Dual Effects of Antioxidants in Neurodegeneration: Direct Neuroprotection against Oxidative Stress and Indirect Protection via Suppression of Gliamediated Inflammation

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