Neuroprotective Effect of Apolipoprotein D in Cuprizone-Induced Cell Line Models: A Potential Therapeutic Approach for Multiple Sclerosis and Demyelinating Diseases

Apolipoprotein D (Apo D) overexpression is a general finding across neurodegenerative conditions so the role of this apolipoprotein in various neuropathologies such as multiple sclerosis (MS) has aroused a great interest in last years. However, its mode of action, as a promising compound for the development of neuroprotective drugs, is unknown. The aim of this work was to address the potential of Apo D to prevent the action of cuprizone (CPZ), a toxin widely used for developing MS models, in oligodendroglial and neuroblastoma cell lines. On one hand, immunocytochemical quantifications and gene expression measures showed that CPZ compromised neural mitochondrial metabolism but did not induce the expression of Apo D, except in extremely high doses in neurons. On the other hand, assays of neuroprotection demonstrated that antipsychotic drug, clozapine, induced an increase in Apo D synthesis only in the presence of CPZ, at the same time that prevented the loss of viability caused by the toxin. The effect of the exogenous addition of human Apo D, once internalized, was also able to directly revert the loss of cell viability caused by treatment with CPZ by a reactive oxygen species (ROS)-independent mechanism of action. Taken together, our results suggest that increasing Apo D levels, in an endo- or exogenous way, moderately prevents the neurotoxic effect of CPZ in a cell model that seems to replicate some features of MS which would open new avenues in the development of interventions to afford MS-related neuroprotection.

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M17 human neuroblastoma cell as a cell model for investigation of Botulinum Neurotoxin A activity and evaluation of BoNT/A specific antibody

The Botulinum J ◽

10.1504/tbj.2008.018955 ◽

2008 ◽

Vol 1 (1) ◽

pp. 135 ◽

Cited By ~ 6

Author(s):

Jong O Lee ◽

Johanna Rosenfield ◽

Saul Tzipori ◽

Jong Beak Park

Keyword(s):

Specific Antibody ◽

Botulinum Neurotoxin ◽

Cell Model ◽

Neuroblastoma Cell ◽

Human Neuroblastoma Cell ◽

Botulinum Neurotoxin A ◽

Human Neuroblastoma ◽

A Cell

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Effects of multiple sclerosis in pregnant and post-birth: particularities of the disease activity

10.5327/1516-3180.704 ◽

2021 ◽

Author(s):

Bianca Barbosa Araldi ◽

Victor Hugo Gomes ◽

Bruno Ludvig Vieira ◽

Klesia Adayani Rodrigues ◽

Andressa Gabrieli da Silva ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Neurological Diseases ◽

Neuroprotective Effect ◽

Cumulative Effect ◽

Demyelinating Diseases ◽

Hormonal Changes ◽

Neuroprotective Effects ◽

Maternal Immune System ◽

The Central Nervous System

Introduction: Demyelinating diseases are a heterogeneous group of neurological diseases related to autoimmunity whose representative is Multiple Sclerosis (MS). It is characterized by an immune-mediated demyelination of the central nervous system, with a typical outbreak and remission clinic. During pregnancy, a reduction in disease activity was noted due to immunomodulatory effects, and an increase in outbreaks in the puerperium. Thus, our goal is to demonstrate the relationship between pregnancy and MS. Methods: This is a systematic bibliographic review based on searching the SCIELO, PUBMED and UPTODATE databases using the words “Multiple Sclerosis”, “Pregnancy”, “Demyelinating diseases” and “Neurological Disorders”. Discussion: Pregnancy is responsible for numerous changes in the maternal body resulting from hormonal changes with an immunological and neuroprotective effect. Until the beginning of the 20th century, it was considered a risk factor or precipitator of outbreaks in these patients. In 1950, Tillmann et al. questioned him and concluded that pregnancy reduces the risk of outbreaks of the disease and that relapses were more associated with postpartum. The question is still raised by several authors, due to their interest in the search for intricate protective factors in the genesis and cure of the disease. It is believed that immunological changes in pregnancy tend to suppress the maternal immune system preventing fetal rejection, and together with gestational hormones, they are able to make neuronal tissue more resistant to inflammatory aggression and greater capacity for cell repair. In the puerperium, there was an increase in outbreaks of the disease, probably associated with a reduction in hormone levels, the effects of which are lost after the elimination of the fetus. Breastfeeding is not associated with the prevention or risk of new MS outbreaks. The frequency of outbreaks before conception is the only independent predictor of new post-term episodes. There is no consensus regarding the therapeutic approach in these pregnant women. Conclusion: Evidence supports the association between pregnancy, reduced activity of MS and increased activity in the 3 months postpartum, due to the probable loss of neuroprotective effects associated with hormones. Recommendations regarding the use of immunomodulator are suspended before conception (“washout”) until term. New evidence did not associate the use of interferon-β with abortion, cesarean section or low birth weight. There was a benefit of long-term parity with a cumulative effect on the patient’s immunohumor modulation.

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Suppression of Progranulin Expression Leads to Formation of Intranuclear TDP-43 Inclusions In Vitro: A Cell Model of Frontotemporal Lobar Degeneration

Journal of Neuropathology & Experimental Neurology ◽

10.1093/jnen/nlz102 ◽

2019 ◽

Vol 78 (12) ◽

pp. 1124-1129

Author(s):

Jiuling Zhu ◽

Ning Wang ◽

Xianan Li ◽

Xiaojing Zheng ◽

Junli Zhao ◽

...

Keyword(s):

Cell Line ◽

Frontotemporal Lobar Degeneration ◽

Cell Model ◽

Neuroblastoma Cell ◽

Brain Regions ◽

Neuroblastoma Cell Line ◽

Null Alleles ◽

Intranuclear Inclusions ◽

A Cell

Abstract Mutations in the GRN gene coding for progranulin (PGRN) are responsible for many cases of familial frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein 43 (TDP-43)-positive inclusions (FTLD-TDP). GRN mutations create null alleles resulting in decreased progranulin protein or haploinsufficiency. FTLD-TDP with GRN mutations is characterized by lentiform neuronal intranuclear inclusions that are positive for TDP-43 in affected brain regions. In this study, by stably expressed short hairpin RNA, we established a neuroblastoma cell line with decreased PGRN level. This cell line reveals TDP-43-positive intranuclear inclusions. In addition, replacement with purified PGRN protein restores normal TDP-43 nuclear distribution. This cell model can be valuable for the study of the role of PGRN in the pathogenesis in FTLD-TDP.

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Neuroprotective Effects of Propylgallate Against Oxidative Stress in Retinal Ganglion Cells

10.21203/rs.3.rs-870585/v1 ◽

2021 ◽

Author(s):

Zhanjun Lu ◽

Qin Xiao ◽

Jinsong Lu ◽

Chun Tao ◽

Ruitong Ma ◽

...

Keyword(s):

Oxidative Stress ◽

Optic Nerve ◽

Molecular Mechanism ◽

Target Genes ◽

Vision Loss ◽

Ganglion Cells ◽

Cell Model ◽

Neuroprotective Effect ◽

Neuroprotective Effects ◽

Neuroprotective Drugs

Abstract Background: Diabetic retinopathy is a group of eye diseases which result in damage to the optic nerve and vision loss, it has seriously affect peoples' health. The purpose of this study is to contrast the neuroprotective effects of curcumin, gastrodin, propylgallate, adenosine. At the same time, we preliminarily explore the molecular mechanism of protective drugs.Methods: In this study, we used 500μM H2O2 treated RGC-5 cells to induce a cellular oxidative stress model. We treated this cell model with four drug monomers: Propylgallate, Curcumin, Gastrodin and Adenosine to find drug monomers with neuroprotective effect. We used apoptosis PCR array to obtain apoptosis related genes regulated by neuroprotective drugs.Results: We found the Propylgallate treated RGC-5 cells had highest survival rate when compared to Curcumin, Gastrodin, Adenosine treated RGC-5 cells.In addition, it had lowest cell cytotoxicity and apoptotic rate when compared to Curcumin, Gastrodin, Adenosine treated RGC-5 cells.Moreover, the expression of ROS in Propylgallate treated RGC-5 cells was lowest when compared to Curcumin, Gastrodin, Adenosine treated RGC-5 cells. We found that Caspase-3, Caspase-8, and Caspase-9 are the main target genes of Propylgallate which can preliminarily explain the neuroprotective mechanism of Propylgallate against apoptosis..Conclusion: The present study revealed that the propylgallate has best neuroprotective effects, it may provide a promissing drug to prevent and improve the damage of optic nerve. In this article, we also preliminarily expounded the neuroprotective molecular mechanism of Propylgallate.

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Evidence for a Novel Intrapituitary Autocrine/Paracrine Feedback Loop Regulating Growth Hormone Synthesis and Secretion in Grass Carp Pituitary Cells by Functional Interactions between Gonadotrophs and Somatotrophs

Endocrinology ◽

10.1210/en.2004-0362 ◽

2004 ◽

Vol 145 (12) ◽

pp. 5548-5559 ◽

Cited By ~ 35

Author(s):

Hong Zhou ◽

Xinyan Wang ◽

Wendy K. W. Ko ◽

Anderson O. L. Wong

Keyword(s):

Mrna Expression ◽

Grass Carp ◽

Feedback Loop ◽

Cell Model ◽

Pituitary Cells ◽

Mrna Levels ◽

Local Interactions ◽

Hormone Synthesis ◽

A Cell ◽

High Doses

Abstract Gonadotropin (GTH) and GH released from the pituitary are known to interact at multiple levels to modulate the functions of the gonadotrophic and somatotrophic axes. However, their interactions at the pituitary level have not been fully characterized. In this study, autocrine/paracrine regulation of GH synthesis and secretion by local interactions between gonadotrophs and somatotrophs was examined using grass carp pituitary cells as a cell model. Exogenous GTH and GH induced GH release and GH mRNA expression in carp pituitary cells. Removal of endogenous GTH and GH by immunoneutralization with GTH and GH antisera, respectively, suppressed GH release, GH production, and GH mRNA levels. GH antiserum also blocked the stimulatory effects of exogenous GTH on GH release and GH mRNA levels. In reciprocal experiments, GH release and GH mRNA expression induced by exogenous GH was significantly reduced by GTH antiserum. In addition, exogenous GH was found to be inhibitory to basal GTH release and treatment with GH antiserum elevated GTH secretion at low doses but suppressed GTH production at high doses. These results suggest that local interactions between gonadotrophs and somatotrophs may form an intrapituitary feedback loop to regulate GH release and synthesis. In this model, GTH released from gonadotrophs induces GH release and GH production in neighboring somatotrophs. GH secreted maintains somatotroph sensitivity to GTH stimulation, and at the same time, inhibits basal GTH release in gonadotrophs. This feedback loop may represent a novel mechanism regulating GH release and synthesis in lower vertebrates.

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