Progressive multiple sclerosis cerebrospinal fluid induces inflammatory demyelination, axonal loss, and astrogliosis in mice

Cristofanilli, Massimiliano; Rosenthal, Hannah E.; Cymring, Barbara; Gratch, Daniel; Pagano, Benjamin; Xie, Boxun; Sadiq, Saud

doi:10.1016/j.expneurol.2014.07.020

Cited by 21 publications

(18 citation statements)

References 37 publications

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“…2 Paradoxically, astrocytes can also become rapidly activated following exposure to diverse toxic stimuli, leading in turn, to a pathological state termed as reactive astrocytosis that is characterized by upregulation of the intermediate filament proteins GFAP (glial fibrillary acidic protein) and VIM (vimentin), both of which are associated with cellular hypertrophy and proliferation. 3 In addition, astrocytosis has been reported as a hallmark feature underlying various psychiatric and neurological disorders, such as Alzheimer disease, 4 amyotrophic lateral sclerosis, 5 cerebral ischemia, 6 epilepsy, 7 HIV infection, 8 multiple sclerosis, 9 and Parkinson disease. 10 Cocaine binds and inhibits the dopamine transporter activity resulting in elevation of synaptic dopamine concentration leading, in turn, to increased excitability of D1-type neurons in the striatum.…”

Section: Introductionmentioning

confidence: 99%

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

2016

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Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation.

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Section: Introductionmentioning

confidence: 99%

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

2016

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“…In the cerebrospinal fluid (CSF) of MS patients, the expression level of cytokines was shown to be upregulated, and direct injection of CSF from MS patients into mouse brain induced demyelination (Cristofanilli et al, 2014). However, in cell culture experiments, CSF from MS patients promoted neuronal and oligodendrocyte differentiation when incubated with neural precursor cells (Cristofanilli et al, 2013).…”

Section: Factors Affecting Remyelination After Strokementioning

confidence: 99%

Mechanisms of cell–cell interaction in oligodendrogenesis and remyelination after stroke

et al. 2015

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White matter damage is a clinically important aspect of several central nervous system diseases, including stroke. Cerebral white matter primarily consists of axonal bundles ensheathed with myelin secreted by mature oligodendrocytes, which play an important role in neurotransmission between different areas of gray matter. During the acute phase of stroke, damage to oligodendrocytes leads to white matter dysfunction through the loss of myelin. On the contrary, during the chronic phase, white matter components promote an environment, which is favorable for neural repair, vascular remodeling, and remyelination. For effective remyelination to take place, oligodendrocyte precursor cells (OPCs) play critical roles by proliferating and differentiating into mature oligodendrocytes, which help to decrease the burden of axonal injury. Notably, other types of cells contribute to these OPC responses under the ischemic conditions. This mini-review summarizes the non-cell autonomous mechanisms in oligodendrogenesis and remyelination after white matter damage, focusing on how OPCs receive support from their neighboring cells.

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“…MS is characterized by inflammation, demyelination and axonal damage wherein CNS lesions develop that contain a high number of infiltrating auto-reactive cells (Brück 2005;Stadelmann et al 2011;Cristofanilli et al 2014). The pathogenesis of MS is due, in part, to aberrant autoreactive T-cell responses and a subsequent loss of/reduction in function of the regulatory network of the immune system.…”

Section: Introductionmentioning

confidence: 99%

St. John’s wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

Nosratabadi

Rastin

Sankian

et al. 2015

Journal of Immunotoxicology

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Multiple sclerosis (MS) is a central nervous system disorder mainly characterized by inflammation, demyelination and axonal injury. Anti-inflammatory agents can be used to ameliorate the disease process. Hypericum perforatum L or St. John's wort is widely used as an anti-depressant and antiinflammatory remedy in traditional and herbal medicine. Based on St. John's wort properties, the therapeutic potentials of an H. perforatum extract (HPE) and a single component, hyperforin were evaluated for effectiveness against MOG 35-55 -induced experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Female C57BL/6 mice were immunized with specific antigen MOG 35-55 and then administered different doses of hyperforin or HPE postimmunization. Clinical symptoms/other relevant parameters were assessed daily. Histological analysis of the spinal cord was performed. T-cell proliferative activity was also evaluated using a BrdU assay. The effect of hyperforin on regulatory T-cells (T reg cells) was assessed using flow cytometry. The results indicate hyperforin and HPE reduced the incidence and severity of EAE, an outcome that closely correlated with an inhibition of pathological features (leukocyte infiltration and demyelination) and antigen-specific T-cell proliferation. The study also showed that hyperforin caused increased T reg cell levels in the spleen. These results indicated that hyperforin and HPE could attenuate EAE autoimmune responses by inhibiting immune cell infiltration and expansion of T reg cell and could eventually be considered as a potential candidate for use in the treatment of MS. ARTICLE HISTORY

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Progressive multiple sclerosis cerebrospinal fluid induces inflammatory demyelination, axonal loss, and astrogliosis in mice

Cited by 21 publications

References 37 publications

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

Mechanisms of cell–cell interaction in oligodendrogenesis and remyelination after stroke

St. John’s wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

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