scholarly journals Neuroprotection Comparison of Rosmarinic Acid and Carnosic Acid in Primary Cultures of Cerebellar Granule Neurons

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2956 ◽  
Author(s):  
Faten Taram ◽  
Elizabeth Ignowski ◽  
Nathan Duval ◽  
Daniel Linseman
Keyword(s):  
Rosmarinic Acid ◽  
Nitrosative Stress ◽  
Primary Cultures ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Carnosic Acid ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Neuroprotective Effects ◽  
Cerebellar Granule

Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Parkinson’s disease, are characterized by the progressive loss of neurons in specific regions of the brain and/or spinal cord. Neuronal cell loss typically occurs by either apoptotic or necrotic mechanisms. Oxidative stress and nitrosative stress, along with excitotoxicity and caspase activation, have all been implicated as major underlying causes of neuronal cell death. Diverse nutraceuticals (bioactive compounds found in common foods) have been shown to have neuroprotective effects in a variety of in vitro and in vivo disease models. In the current study, we compared the neuroprotective effects of two polyphenolic compounds, rosmarinic acid and carnosic acid, which are both found at substantial concentrations in the herb rosemary. The capacity of these compounds to rescue primary cultures of rat cerebellar granule neurons (CGNs) from a variety of stressors was investigated. Both polyphenols significantly reduced CGN death induced by the nitric oxide donor, sodium nitroprusside (nitrosative stress). Rosmarinic acid uniquely protected CGNs from glutamate-induced excitotoxicity, while only carnosic acid rescued CGNs from caspase-dependent apoptosis induced by removal of depolarizing extracellular potassium (5K apoptotic condition). Finally, we found that carnosic acid protects CGNs from 5K-induced apoptosis by activating a phosphatidylinositol 3-kinase (PI3K) pro-survival pathway. The shared and unique neuroprotective effects of these two compounds against diverse modes of neuronal cell death suggest that future preclinical studies should explore the potential complementary effects of these rosemary polyphenols on neurodegenerative disease progression.

Roles of cyclin-dependent kinase 4 and p53 in neuronal cell death induced by doxorubicin on cerebellar granule neurons in mouse

2004 ◽  
Vol 365 (3) ◽  
pp. 180-185 ◽  
Author(s):  
Yuko Otsuka ◽  
Tomoaki Tanaka ◽  
Daigaku Uchida ◽  
Yoshihiko Noguchi ◽  
Naokatsu Saeki ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Cyclin Dependent Kinase ◽  
Cerebellar Granule

scholarly journals Curcumin Pretreatment Induces Nrf2 and an Antioxidant Response and Prevents Hemin-Induced Toxicity in Primary Cultures of Cerebellar Granule Neurons of Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Susana González-Reyes ◽  
Silvia Guzmán-Beltrán ◽  
Omar Noel Medina-Campos ◽  
José Pedraza-Chaverri
Keyword(s):  
Protective Effect ◽  
Heme Oxygenase ◽  
Curcuma Longa ◽  
Primary Cultures ◽  
Buthionine Sulfoximine ◽  
Antioxidant Response ◽  
Cerebellar Granule Neurons ◽  
Heme Oxygenase 1 ◽  
Granule Neurons ◽  
Cerebellar Granule

Curcumin is a bifunctional antioxidant derived fromCurcuma longa. This study identifies curcumin as a neuroprotectant against hemin-induced damage in primary cultures of cerebellar granule neurons (CGNs) of rats. Hemin, the oxidized form of heme, is a highly reactive compound that induces cellular injury. Pretreatment of CGNs with 5–30 μM curcumin effectively increased by 2.3–4.9 fold heme oxygenase-1 (HO-1) expression and by 5.6–14.3-fold glutathione (GSH) levels. Moreover, 15 μM curcumin attenuated by 55% the increase in reactive oxygen species (ROS) production, by 94% the reduction of GSH/glutathione disulfide (GSSG) ratio, and by 49% the cell death induced by hemin. The inhibition of heme oxygenase system or GSH synthesis with tin mesoporphyrin and buthionine sulfoximine, respectively, suppressed the protective effect of curcumin against hemin-induced toxicity. These data strongly suggest that HO-1 and GSH play a major role in the protective effect of curcumin. Furthermore, it was found that 24 h of incubation with curcumin increases by 1.4-, 2.3-, and 5.2-fold the activity of glutathione reductase, glutathione S-transferase and superoxide dismutase, respectively. Additionally, it was found that curcumin was capable of inducing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus. These data suggest that the pretreatment with curcumin induces Nrf2 and an antioxidant response that may play an important role in the protective effect of this antioxidant against hemin-induced neuronal death.

scholarly journals Anti-inflammatory and Neuroprotective Effects of Fungal Immunomodulatory Protein Involving Microglial Inhibition

2018 ◽  
Vol 19 (11) ◽  
pp. 3678 ◽  
Author(s):  
Wen-Ying Chen ◽  
Cheng-Yi Chang ◽  
Jian-Ri Li ◽  
Jiaan-Der Wang ◽  
Chih-Cheng Wu ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Tyrosine Phosphatase ◽  
Primary Cultures ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuroprotective Effects ◽  
Fungal Immunomodulatory Protein ◽  
Immunomodulatory Protein ◽  
Anti Inflammatory

Microglia polarization of classical activation state is crucial to the induction of neuroinflammation, and has been implicated in the pathogenesis of numerous neurodegenerative diseases. Fungal immunomodulatory proteins are emerging health-promoting natural substances with multiple pharmacological activities, including immunomodulation. Herein, we investigated the anti-inflammatory and neuroprotective potential of fungal immunomodulatory protein extracted from Ganoderma microsporum (GMI) in an in vitro rodent model of primary cultures. Using primary neuron/glia cultures consisting of neurons, astrocytes, and microglia, a GMI showed an alleviating effect on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced inflammatory mediator production and neuronal cell death. The events of neuroprotection caused by GMI were accompanied by the suppression of Nitric Oxide (NO), Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), and Prostaglandin E2 (PGE2) production, along with the inhibition of microglia activation. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by GMI was accompanied by the resolution of oxidative stress, the preservation of protein tyrosine phosphatase and serine/threonine phosphatase activity, and the reduction of NF-κB, AP-1, cyclic AMP response element-binding protein (CREB), along with signal transducers and activators of transcription (Stat1) transcriptional activities and associated upstream activators. These findings suggest that GMI may have considerable potential towards the treatment of neuroinflammation-mediated neurodegenerative diseases.

scholarly journals Neuroglobin Plays a Protective Role in Arsenite-Induced Cytotoxicity by Inhibition of Cdc42 and Rac1GTPases in Rat Cerebellar Granule Neurons

2015 ◽  
Vol 36 (4) ◽  
pp. 1613-1627 ◽  
Author(s):  
Xiaona Liu ◽  
Yanhui Gao ◽  
Yuan An ◽  
Xiaoyan Fu ◽  
Yuanyuan Li ◽  
...  
Keyword(s):  
Western Blot ◽  
Rho Gtpases ◽  
Primary Cultures ◽  
Protective Role ◽  
Cell Counting ◽  
Cerebellar Granule Neurons ◽  
Tunel Staining ◽  
Granule Neurons ◽  
Cytotoxic Effects ◽  
Cerebellar Granule

Background and Aims: We have previously shown that neuroglobin (Ngb) expression can be regulated by sodium arsenite (NaAsO2) exposure in rat cerebellar granule neurons (CGNs). However, the precise molecular mechanisms of Ngb action are largely unknown. Ras homolog (Rho) guanosine triphosphatases (Rho GTPases) are involved in the regulation of a number of cellular processes, including cell cytotoxicity. It has been reported that Ngb can act as a guanine nucleotide dissociation inhibitior (GDI) role to inactivate Rho GTPases. Therefore, we investigated Rho GTPases activation induced by NaAsO2 exposure in rat CGNs and effects of Rho GTPases activation on the cells. We also investigated the role of Ngb in this process. Methods: Primary cultures of CGNs were prepared from 7-day-old Wistar rat pups. The cytotoxic effects of NaAsO2 on CGNs were evaluated using the Cell Counting Kit-8 assay and TUNEL staining. RNA interference technology was used to silence Ngb, and the subsequent effects were evaluated by quantitative RT-PCR and Western blot. Cdc42 and Rac1 activation were measured by pull-down assay and Western blot. Results: NaAsO2 induced cytotoxicity in rat CGNs, increased GTP-bound form of Cdc42 and Rac1 GTPases in the cells. Furthermore, inhibition of Cdc42 or Rac1 activity using the inhibitor ZCL278 or NSC23766 decreased apoptosis and increased cell viability in the cells exposed to NaAsO2. Using siRNA-mediated knockdown, we show that NaAsO2-induced cytotoxicity was exacerbated, activation of Cdc42 (GTP-Cdc42) and Rac1 (GTP-Rac1) was increased in Ngb RNA silencing cells. Conclusions: cytotoxic effects of NaAsO2 on rat CGNs is induced at least partly by Cdc42 and Rac1 activation, and Ngb can inhibit Cdc42 and Rac1 activation to play protective role in rat CGNs exposed to NaAsO2.

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