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Fulltext Analysis of expression of vitamin E-binding proteins in H2O2 induced SK-N-SH neuronal cells supplemented with α-tocopherol and tocotrienol-rich fraction

Chiroma AA, Khaza'ai H, Abd Hamid R, Chang SK, Zakaria ZA, Zainal Z

PLoS One, 2020;15(11):e0241112.
PMID: 33232330 DOI: 10.1371/journal.pone.0241112

Natural α-tocopherol (α-TCP), but not tocotrienol, is preferentially retained in the human body. α-Tocopherol transfer protein (α-TTP) is responsible for binding α-TCP for cellular uptake and has high affinity and specificity for α-TCP but not α-tocotrienol. The purpose of this study was to examine the modification of α-TTP together with other related vitamin E-binding genes (i.e., TTPA, SEC14L2, and PI-TPNA) in regulating vitamin E uptake in neuronal cells at rest and under oxidative stress. Oxidative stress was induced with H2O2 for an hour which was followed by supplementation with different ratios of α-TCP and tocotrienol-rich fraction (TRF) for four hours. The cellular levels of vitamin E were quantified to determine bioavailability at cellular levels. The expression levels of TTPA, SEC14L2, and PI-TPNA genes in 0% α-TCP were found to be positively correlated with the levels of vitamin E in resting neuronal cells. In addition, the regulation of all the above-mentioned genes affect the distribution of vitamin E in the neuronal cells. It was observed that, increased levels of α-TCP secretion occur under oxidative stress. Thus, our results showed that in conclusion vitamin E-binding proteins may be modified in the absence of α-TCP to produce tocotrienols (TCT), as a source of vitamin E. The current study suggests that the expression levels of vitamin E transport proteins may influence the cellular concentrations of vitamin E levels in the neuronal cells.

Matched MeSH terms: Neurons/drug effects*
Fulltext Role of excitatory amino acid input in rostral ventrolateral medulla neurons in rats with obesity-induced hypertension

Suhaimi FW, Yusoff NH, Dewa A, Yusof AP

Acta Neurol Belg, 2010 Mar;110(1):57-64.
PMID: 20514927

Obesity is intimately associated with hypertension; increases in blood pressure are closely related to the magnitude of weight gain. The present study aims to determine whether the excitatory amino acid input to rostral ventrolateral medulla (RVLM) contributes to elevated blood pressure in rats with diet-induced obesity. Male Sprague-Dawley rats weighing 280 to 300 grams were fed with a low-fat diet (10% kcal from fat) or moderately high-fat diet (32% kcal from fat) for 16 weeks. At week 16, rats on the moderate high-fat diet were segregated into obesity-prone and obesity-resistant rats based on body weight distribution. Baseline mean arterial pressure (MAP) was significantly higher in obesity-prone rats as compared to obesity-resistant and rats on a low-fat diet. Bilateral injection of kynurenic acid (KYN) (40 nM) into the RVLM of the obesity-prone rats reduced MAP to levels significantly different from those observed in rats on a low-fat diet and obesity-resistant rats (no change in MAP). At a lower concentration (4 nM), KYN injection did not produce any change in MAP in any group. The results obtained suggest that excitatory amino acid input to the RVLM does contribute to the development of hypertension in rats with diet-induced obesity.

Matched MeSH terms: Neurons/drug effects
Flavonoids and its Neuroprotective Effects on Brain Ischemia and Neurodegenerative Diseases

Putteeraj M, Lim WL, Teoh SL, Yahaya MF

Curr Drug Targets, 2018;19(14):1710-1720.
PMID: 29577854 DOI: 10.2174/1389450119666180326125252

Brain ischemia is among the leading cause of death with majority of the cases are associated with ischemic strokes. It can occur in two forms of either focal or global ischemia. Neurodegenerative disorder such as Alzheimer and Parkinson diseases is also on the rise worldwide. These disorders have common similarities; i.e. they all affecting the central nervous system with debilitating effect to the patient. In this review, we look into the promising role of flavonoids, a natural bioactive compound found abundant in vegetables, fruits and traditional herbs. Treatment with flavonoids such as curcumin, lycopene, ginsenoside, vitexin and baicalin have shown promising neuroprotective effects against ischemic-induced injury. Besides anticancer, antioxidant and immunomodulation properties, flavonoid also exerts neuroprotective effects by increases neuronal viability, increases tissue perfusion and cerebral blood flow and reduce ischemic-related apoptosis. In addition, flavonoid also exerts anti-amyloidogenic effect and reduces loss of dopaminergic neurons in the brain. These results suggesting flavonoids might be able to serve as a potential therapeutic agent in brain disorders.

Matched MeSH terms: Neurons/drug effects
Fulltext Neuroprotective effects of Hericium erinaceus (Bull.: Fr.) Pers. against high-dose corticosterone-induced oxidative stress in PC-12 cells

Lew SY, Lim SH, Lim LW, Wong KH

BMC Complement Med Ther, 2020 Nov 11;20(1):340.
PMID: 33176761 DOI: 10.1186/s12906-020-03132-x

BACKGROUND: Hericium erinaceus is a culinary and medicinal mushroom in Traditional Chinese Medicines. It has numerous pharmacological effects including immunomodulatory, anti-tumour, anti-microbial, anti-aging and stimulation of nerve growth factor (NGF) synthesis, but little is known about its potential role in negating the detrimental effects of oxidative stress in depression. The present study investigated the neuroprotective effects of H. erinaceus standardised aqueous extract (HESAE) against high-dose corticosterone-induced oxidative stress in rat pheochromocytoma (PC-12) cells, a cellular model mimicking depression.
METHODS: PC-12 cells was pre-treated with HESAE for 48 h followed by 400 μM corticosterone for 24 h to induce oxidative stress. Cells in complete medium without any treatment or pre-treated with 3.125 μg/mL desipramine served as the negative and positive controls, respectively. The cell viability, lactate dehydrogenase (LDH) release, endogenous antioxidant enzyme activities, aconitase activity, mitochondrial membrane potentials (MMPs), intracellular reactive oxygen species (ROS) levels and number of apoptotic nuclei were quantified. In addition, HESAE ethanol extract was separated into fractions by chromatographic methods prior to spectroscopic analysis.
RESULTS: We observed that PC-12 cells treated with high-dose corticosterone at 400 μM had decreased cell viability, reduced endogenous antioxidant enzyme activities, disrupted mitochondrial function, and increased oxidative stress and apoptosis. However, pre-treatment with HESAE ranging from 0.25 to 1 mg/mL had increased cell viability, decreased LDH release, enhanced endogenous antioxidant enzyme activities, restored MMP, attenuated intracellular ROS and protected from ROS-mediated apoptosis. The neuroprotective effects could be attributed to significant amounts of adenosine and herierin III isolated from HESAE.
CONCLUSIONS: HESAE demonstrated neuroprotective effects against high-dose corticosterone-induced oxidative stress in an in vitro model mimicking depression. HESAE could be a potential dietary supplement to treat depression.

Matched MeSH terms: Neurons/drug effects*
Is vitamin E toxic to neuron cells?

Then SM, Mazlan M, Mat Top G, Wan Ngah WZ

Cell Mol Neurobiol, 2009 Jun;29(4):485-96.
PMID: 19172392 DOI: 10.1007/s10571-008-9340-8

Besides acting as potent free radical scavengers, tocopherols and tocotrienols have been known to have non-antioxidant properties such as the involvement of alpha-tocopherol (alphaT) in PKC pathway and the anti-cancer properties of gamma-tocotrienol (gammaT3). This study aims to elucidate whether protective effects shown by alphaT and gammaT3 in H(2)O(2)-induced neuron cultures have anti-apoptotic or pro-apoptotic tendency toward the initiation of neuronal apoptosis. H(2)O(2) is used to induce apoptosis in primary cerebellar neuron cultures which is attenuated by pretreatment of alphaT or gammaT3 at concentrations < or =10 microM. Similar to our previous work, gammaT3 was found to be neurotoxic at concentrations > or =100 microM, whereas alphaT showed no neurotoxicity. Cellular uptake of gammaT3 was higher than that of alphaT. Treating cells simultaneously with either gammaT3 or alphaT and with then H(2)O(2) led to higher expression of Bax and Bcl-2 than in neurons exposed to H(2)O(2) alone. Analysis of Bcl-2/Bax ratio as 'survival index' showed that both pretreatment of gammaT3 and alphaT followed by H(2)O(2) increase the 'survival index' of Bcl-2/Bax ratio compared to H(2)O(2)-treated cells, while treatment of gammaT3 alone decrease the ratio compared to unchanged Bcl2/Bax ratio of similar treatment with alphaT alone. Similar treatment of gammaT3 decreased p53 expression and activates p38 MAPK phosphorylation, whereas alphaT did not alter its expression compared to H(2)O(2)-treated cells. Treating neurons with only gammaT3 or alphaT increased the expression of Bax, Bcl-2, p53, and p38 MAPK compared to control with gammaT3 exerting stronger expression for proteins involved than alphaT. In conclusion, low doses of gammaT3 and alphaT confer neuroprotection to H(2)O(2)-treated neurons via their antioxidant mechanism but gammaT3 has stronger pro-apoptosis tendency than alphaT by activating molecules involved in the neuronal apoptotic pathway in the absence of H(2)O(2).

Matched MeSH terms: Neurons/drug effects*
Fulltext In vitro differentiation between oxytocin- and vasopressin-secreting magnocellular neurons requires more than one experimental criterion

da Silva MP, Merino RM, Mecawi AS, Moraes DJ, Varanda WA

Mol Cell Endocrinol, 2015 Jan 15;400:102-11.
PMID: 25451978 DOI: 10.1016/j.mce.2014.11.004

The phenotypic differentiation between oxytocin (OT)- and vasopressin (VP)-secreting magnocellular neurosecretory cells (MNCs) from the supraoptic nucleus is relevant to understanding how several physiological and pharmacological challenges affect their electrical activity. Although the firing patterns of OT and VP neurons, both in vivo and in vitro, may appear different from each other, much is assumed about their characteristics. These assumptions make it practically impossible to obtain a confident phenotypic differentiation based exclusively on the firing patterns. The presence of a sustained outward rectifying potassium current (SOR) and/or an inward rectifying hyperpolarization-activated current (IR), which are presumably present in OT neurons and absent in VP neurons, has been used to distinguish between the two types of MNCs in the past. In this study, we aimed to analyze the accuracy of the phenotypic discrimination of MNCs based on the presence of rectifying currents using comparisons with the molecular phenotype of the cells, as determined by single-cell RT-qPCR and immunohistochemistry. Our results demonstrated that the phenotypes classified according to the electrophysiological protocol in brain slices do not match their molecular counterparts because vasopressinergic and intermediate neurons also exhibit both outward and inward rectifying currents. In addition, we also show that MNCs can change the relative proportion of each cell phenotype when the system is challenged by chronic hypertonicity (70% water restriction for 7 days). We conclude that for in vitro preparations, the combination of mRNA detection and immunohistochemistry seems to be preferable when trying to characterize a single MNC phenotype.

Matched MeSH terms: Neurons/drug effects
Fulltext Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH neuronal cell line, GT1-7

Son YL, Ubuka T, Soga T, Yamamoto K, Bentley GE, Tsutsui K

FASEB J, 2016 06;30(6):2198-210.
PMID: 26929433 DOI: 10.1096/fj.201500055

Gonadotropin-inhibitory hormone (GnIH) acts as a negative regulator of reproduction by acting on gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its functional significance, the molecular mechanism of GnIH action in the target cells has not been fully elucidated. To expand our previous study on GnIH actions in gonadotropes, we investigated the potential signal transduction pathway that conveys the inhibitory action of GnIH in GnRH neurons by using the GnRH neuronal cell line, GT1-7. We examined whether GnIH inhibits the action of kisspeptin and vasoactive intestinal polypeptide (VIP), positive regulators of GnRH neurons. Although GnIH significantly suppressed the stimulatory effect of kisspeptin on GnRH release in hypothalamic culture, GnIH had no inhibitory effect on kisspeptin stimulation of serum response element and nuclear factor of activated T-cell response element activities and ERK phosphorylation, indicating that GnIH may not directly inhibit kisspeptin signaling in GnRH neurons. On the contrary, GnIH effectively eliminated the stimulatory effect of VIP on p38 and ERK phosphorylation, c-Fos mRNA expression, and GnRH release. The use of pharmacological modulators strongly demonstrated the specific inhibitory action of GnIH on the adenylate cyclase/cAMP/protein kinase A pathway, suggesting a common inhibitory mechanism of GnIH action in GnRH neurons and gonadotropes.-Son, Y. L., Ubuka, T., Soga, T., Yamamoto, K., Bentley, G. E., Tsutsui, K. Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH neuronal cell line, GT1-7.

Matched MeSH terms: Neurons/drug effects*
Gonadotropin-inhibitory hormone mediates behavioral stress responses

Ubuka T, Parhar IS, Tsutsui K

Gen Comp Endocrinol, 2018 09 01;265:202-206.
PMID: 29510150 DOI: 10.1016/j.ygcen.2018.03.004

Gonadotropin-inhibitory hormone (GnIH) is an inhibitor of the hypothalamic-pituitary-gonadal (HPG) axis. GnIH is also called RFamide-related peptide (RFRP) as GnIH peptides have a characteristic C-terminal LPXRFiamide (X = L or Q) sequence. GnIH is thought to be the mediator of stress by negatively regulating the HPG axis as various stressors increase GnIH mRNA, GnIH peptide or GnIH neuronal activity. On the other hand, GnIH may also mediate behavioral stress responses as GnIH neuronal fibers and GnIH receptors are widely located in the limbic system of telencephalon, diencephalon and midbrain area. Previous studies have shown that intracerebroventricular (i.c.v.) administration of GnIH (RFRP) blocks morphine-induced analgesia in hot plate and formalin injection tests in rats suggesting that GnIH increases sensitivity to pain. GnIH (RFRP) also increases anxiety-like behavior in rats. RNA interference of GnIH gene (GnIH RNAi) increases locomotor activity of white-crowned sparrow and Japanese quail and i.c.v. administration of GnIH decreases GnIH RNAi induced locomotor activity. It was further shown that i.c.v. administration of GnIH (RFRP) decreases aggressive behavior in male quail and sexual behavior in male rats, female white-crowned sparrow and female hamsters. These results suggest that GnIH decreases threat to homeostasis of the organism by increasing pain sensitivity, anxiety and decreasing locomotor activity, aggressive behavior and sexual behavior. GnIH may also mediate the effect of stress on behavior.

Matched MeSH terms: Neurons/drug effects
Fulltext A Review on the Relationship between Tocotrienol and Alzheimer Disease

Chin KY, Tay SS

Nutrients, 2018 Jul 09;10(7).
PMID: 29987193 DOI: 10.3390/nu10070881

Alzheimer’s disease (AD) is plaguing the aging population worldwide due to its tremendous health care and socioeconomic burden. Current treatment of AD only offers symptomatic relief to patients. Development of agents targeting specific pathologies of AD is very slow. Tocotrienol, a member of the vitamin E family, can tackle many aspects of AD, such as oxidative stress, mitochondrial dysfunction and abnormal cholesterol synthesis. This review summarizes the current evidence on the role of tocotrienol as a neuroprotective agent. Preclinical studies showed that tocotrienol could reduce oxidative stress by acting as a free-radical scavenger and promoter of mitochondrial function and cellular repair. It also prevented glutamate-induced neurotoxicity in the cells. Human epidemiological studies showed a significant inverse relationship between tocotrienol levels and the occurrence of AD. However, there is no clinical trial to support the claim that tocotrienol can delay or prevent the onset of AD. As a conclusion, tocotrienol has the potential to be developed as an AD-preventing agent but further studies are required to validate its efficacy in humans.

Matched MeSH terms: Neurons/drug effects*
Fucosterol exerts protection against amyloid β-induced neurotoxicity, reduces intracellular levels of amyloid β and enhances the mRNA expression of neuroglobin in amyloid β-induced SH-SY5Y cells

Gan SY, Wong LZ, Wong JW, Tan EL

Int J Biol Macromol, 2019 Jan;121:207-213.
PMID: 30300695 DOI: 10.1016/j.ijbiomac.2018.10.021

Alzheimer's disease (AD) is a neurodegenerative disease that leads to progressive loss of neurons which often results in deterioration of memory and cognitive function. The development of AD is highly associated with the formation of senile plaques and neurofibrillary tangles. Amyloid β (Aβ) induces neurotoxicity and contributes to the development of AD. Recent evidences also highlighted the importance of neuroglobin (Ngb) in ameliorating AD. This study assessed the ability of fucosterol, a phytosterol found in brown alga, in protecting SH-SY5Y cells against Aβ-induced neurotoxicity. Its effects on the mRNA levels of APP and Ngb as well as the intracellular Aβ levels were also determined in Aβ-induced SH-SY5Y cells. SH-SY5Y cells were exposed to fucosterol prior to Aβ treatment. The effect on apoptosis was determined using Annexin V FITC staining and mRNA expression was studied using RT-PCR. Flow cytometry confirmed the protective effects of fucosterol on SH-SY5Y cells against Aβ-induced apoptosis. Pretreatment with fucosterol increased the Ngb mRNA levels but reduced the levels of APP mRNA and intracellular Aβ in Aβ-induced SH-SY5Y cells. These observations demonstrated the protective properties of fucosterol against Aβ-induced neurotoxicity in neuronal cells.

Matched MeSH terms: Neurons/drug effects
Fulltext Effect of tualang honey against KA-induced oxidative stress and neurodegeneration in the cortex of rats

Mohd Sairazi NS, K N S S, Asari MA, Mummedy S, Muzaimi M, Sulaiman SA

BMC Complement Altern Med, 2017 Jan 09;17(1):31.
PMID: 28068984 DOI: 10.1186/s12906-016-1534-x

Administration of KA on rodents has resulted in seizures, behavioral changes, oxidative stress, and neuronal degeneration on selective population of neurons in the brain. The present study was undertaken to investigate the extent of neuroprotective effect conferred by Malaysian Tualang Honey (TH), an antioxidant agent, in the cerebral cortex of rats against KA-induced oxidative stress and neurodegeneration in an animal model of KA-induced excitotoxicity.

Matched MeSH terms: Neurons/drug effects*
The effects of prenatal alcohol exposure on the morphological characteristics of spinal motoneurons

David P, Subramaniam K

Birth Defects Res. Part A Clin. Mol. Teratol., 2009 Sep;85(9):791-9.
PMID: 19452514 DOI: 10.1002/bdra.20593

Clinical studies and research in animals have established that alcohol consumption during pregnancy produces irreversible developmental anomalies. Deficits in fine motor performance are often noted in infants diagnosed with fetal alcohol syndrome. However, the effects of alcohol on the spinal motoneurons have not been examined. In this study, the morphometric alterations in spinal motoneurons were assessed as a result of prenatal alcohol exposure.

Matched MeSH terms: Motor Neurons/drug effects*
Effect of concurrent application of heat, swim stress and repeated dermal application of chlorpyrifos on the hippocampal neurons in mice

Mitra NK, Nadarajah VD, Siong HH

Folia Neuropathol, 2009;47(1):60-8.
PMID: 19353435

Dermal absorption of chlorpyrifos (CPF), an organophosphate (OP) pesticide, is important because of its popular use. Stress has been reported to exacerbate neurotoxic effects of certain OP pesticides; however, quantitative studies to corroborate this are not reported. This study correlates the changes in acetylcholinesterase (AChE) levels and neuronal counts in areas of the hippocampus to consecutive exposure of stress, heat and CPF. Male mice (60 days) were segregated into six groups: one control, one stress control, and four treated groups (n=10). CPF was applied in doses of 1/2 and 1/5 of dermal LD50 (E1 and E2) over the tail of mice under occlusive bandages for 3 weeks. Stress control [(s) C] mice were subjected to swim stress at 38 degrees C (6 mins/day, 3 weeks). (s) E1 and (s) E2 were subjected to swim stress before CPF application. Blood and brain AChE levels were estimated using a spectrofluorometric method (Amplex Red). Pyramidal neurons of the cornu ammonis of the hippocampus under Nissl stain from histological sections were counted per unit area of section and analyzed statistically using one way ANOVA. Swim stress at 38 degrees C aggravated reduction of serum AChE by dermal exposure to CPF by 19.7%. Neurons of CA3 and CA1 regions of the hippocampus showed significant reduction in neuronal counts in (s) E1 and (s) E2 groups compared to E1 and E2 groups. Whereas application of CPF 1/2 dermal LD50 (E1) showed significant reduction of neuronal counts only in the CA3 area.

Matched MeSH terms: Neurons/drug effects*
Deferoxamine Preconditioning of Neural-Like Cells Derived from Human Wharton's Jelly Mesenchymal Stem Cells as a Strategy to Promote Their Tolerance and Therapeutic Potential: An In Vitro Study

Nouri F, Salehinejad P, Nematollahi-Mahani SN, Kamarul T, Zarrindast MR, Sharifi AM

Cell Mol Neurobiol, 2016 Jul;36(5):689-700.
PMID: 26242172 DOI: 10.1007/s10571-015-0249-8

Transplantation of neural-like cells is considered as a promising therapeutic strategy developed for neurodegenerative disease in particular for ischemic stroke. Since cell survival is a major concern following cell implantation, a number of studies have underlined the protective effects of preconditioning with hypoxia or hypoxia mimetic pharmacological agents such as deferoxamine (DFO), induced by activation of hypoxia inducible factor-1 (HIF-1) and its target genes. The present study has investigated the effects of DFO preconditioning on some factors involved in cell survival, angiogenesis, and neurogenesis of neural-like cells derived from human Wharton's jelly mesenchymal stem cells (HWJ-MSCs) in presence of hydrogen peroxide (H2O2). HWJ-MSCs were differentiated toward neural-like cells for 14 days and neural cell markers were identified using immunocytochemistry. HWJ-MSC-derived neural-like cells were then treated with 100 µM DFO, as a known hypoxia mimetic agent for 48 h. mRNA and protein expression of HIF-1 target genes including brain-derived neurotrophic factors (BDNF) and vascular endothelial growth factor (VEGF) significantly increased using RT-PCR and Western blotting which were reversed by HIF-1α inhibitor, while, gene expression of Akt-1, Bcl-2, and Bax did not change significantly but pAkt-1 was up-regulated as compared to poor DFO group. However, addition of H2O2 to DFO-treated cells resulted in higher resistance to H2O2-induced cell death. Western blotting analysis also showed significant up-regulation of HIF-1α, BDNF, VEGF, and pAkt-1, and decrease of Bax/Bcl-2 ratio as compared to poor DFO. These results may suggest that DFO preconditioning of HWJ-MSC-derived neural-like cells improves their tolerance and therapeutic potential and might be considered as a valuable strategy to improve cell therapy.

Matched MeSH terms: Neurons/drug effects
Neuroprotective effect of cerium oxide nanoparticles in a rat model of experimental diabetic neuropathy

Najafi R, Hosseini A, Ghaznavi H, Mehrzadi S, Sharifi AM

Brain Res Bull, 2017 May;131:117-122.
PMID: 28373151 DOI: 10.1016/j.brainresbull.2017.03.013

OBJECTIVE: Neuropathies are a nerve disorders that caused by diabetes. Neuropathy affects over 50% of diabetic patients. High blood glucose and their toxic byproducts are the main causes for nerve dysfunction. In the present study, we examined the neroprotective effects of cerium oxide (CeO2) nanoparticles in diabetic rats.
METHOD: Rats divided into four groups: control group, diabetic group, the diabetic group treated with CeO2nanoparticle at a dose of 65mg/kg and diabetic group received CeO2nanoparticle at a dose of 85mg/kg. Diabetes was induced by single intraperitoneal injection of 65mg/kg streptozotocin (STZ). 8 weeks after the induction of diabetes, body weight and pain sensitivity in all groups were measured. The blood sample was collected for biochemical analysis. The dorsal root ganglion (DRG) neurons were isolated for histopathological stain and morphometric parameters studies.
RESULTS: Reduction of body weight, total thiol molecules (TTM), total antioxidant power (TAP) and ADP/ATP ratio in diabetic rat was reversed by CeO2nanoparticles administration. We showed that lipid peroxidation (LPO) and nociception latency were significantly increased in STZ-treated rats and decreased after CeO2nanoparticles administration. DRG neurons showed obvious vacuole and various changes in diameter, area and the count of A and B cells in STZ-diabetic rat. CeO2nanoparticles improved the histopathology and morphological abnormalities of DRG neurons.
CONCLUSION: Our study concluded the CeO2nanoparticles have a protective effect against the development of DN.

Matched MeSH terms: Neurons/drug effects
Fulltext Studying neuroprotective effect of Atorvastatin as a small molecule drug on high glucose-induced neurotoxicity in undifferentiated PC12 cells: role of NADPH oxidase

Rayegan S, Dehpour AR, Sharifi AM

Metab Brain Dis, 2017 02;32(1):41-49.
PMID: 27476541 DOI: 10.1007/s11011-016-9883-1

Overproduction of reactive oxygen species (ROS) by NADPH oxidase (NOX) activation has been considered the essential mechanism induced by hyperglycemia in various tissues. However, there is no comprehensive study on the role of NOXs in high glucose (HG)-induced toxic effect in neural tissues. Recently, a therapeutic strategy in oxidative related pathologies has been introduced by blocking the undesirable actions of NOX enzymes by small molecules. The protective roles of Statins in ameliorating oxidative stress by NOX inhibition have been shown in some tissues except neural. We hypothesized then, that different NOXs may have role in HG-induced neural cell injury. Furthermore, we postulate that Atorvastatin as a small molecule may modulate this NOXs activity to protect neural cells. Undifferentiated PC12 cells were treated with HG (140 mM/24 h) in the presence and absence of Atorvastatin (1 μM/96 h). The cell viability was measured by MTT assay and the gene and protein expressions profile of NOX (1-4) were determined by RT-PCR and western blotting, respectively. Levels of ROS and malondialdehyde (MDA) were also evaluated. Gene and protein expression levels of NOX (1-4) and consequently ROS and MDA levels were elevated in HG-treated PC12 cells. Atorvastatin could significantly decrease HG-induced NOXs, ROS and MDA elevation and improve impaired cell viability. It can be concluded that HG could elevate NOXs activity, ROS and MDA levels in neural tissues and Atorvastatin as a small molecule NOX inhibitor drug may prevent and delay diabetic complications, particularly neuropathy.

Matched MeSH terms: Neurons/drug effects*
PKC inhibitor reversed the suppressive effect of orexin-A on IPSCs of locus coeruleus neurons in naloxone-induced morphine withdrawal

Davoudi M, Vijeepallam K, Azizi H, Mirnajafi-Zadeh J, Semnanian S

J Neural Transm (Vienna), 2019 11;126(11):1425-1435.
PMID: 31493096 DOI: 10.1007/s00702-019-02064-2

The locus coeruleus (LC) as a target of addictive drugs receives a dense projection of orexinergic fibres from the lateral hypothalamus (LH) and is accordingly a candidate site for the expression of the somatic aspects of morphine withdrawal. Recently it has been shown that the inhibitory synaptic currents of LC neurons decrease partly through orexin type 1 receptors in the context of naloxone-induced morphine withdrawal; however, its cellular mechanism remains unclear. In this study, whole-cell patch clamp recordings of LC neurons in brainstem slices were used to investigate the impact of protein kinase C (PKC) on GABAergic inhibitory post-synaptic currents (IPSCs) in the context of naloxone-induced morphine withdrawal. Male Wistar rats (P14-P21) received morphine (20 mg/kg, i.p.) daily for 7 consecutive days to induce morphine dependency. Our results showed that the application of PKC inhibitor (Go 6983; 1 µM) alone did not decrease the probability of GABA release in the LC neurons of the morphine-treated rats in the presence of naloxone. Although, Go 6983 reversed the reduction of the amplitude of evoked IPSCs (eIPSCs) and spontaneous IPSCs (sIPSCs) frequency induced by orexin-A but did not change the sIPSCs amplitude. These results indicate that the suppressive effect of orexin-A on IPSCs is probably reversed by PKC inhibitor in the LC neurons of morphine-treated rats in the context of naloxone withdrawal.

Matched MeSH terms: Neurons/drug effects
Neuroprotection of α-synuclein under acute and chronic rotenone and maneb treatment is abolished by its familial Parkinson's disease mutations A30P, A53T and E46K

Choong CJ, Say YH

Neurotoxicology, 2011 Dec;32(6):857-63.
PMID: 21658409 DOI: 10.1016/j.neuro.2011.05.012

α-Synuclein (α-Syn) plays a crucial role in the pathophysiology of Parkinson's disease (PD). α-Syn has been extensively studied in many neuronal cell-based PD models but has yielded mixed results. The objective of this study was to re-evaluate the dual cytotoxic/protective roles of α-Syn in dopaminergic SH-SY5Y cells. Stable SH-SY5Y cells overexpressing wild type or familial α-Syn mutants (A30P, E46K and A53T) were subjected to acute and chronic rotenone and maneb treatment. Compared with untransfected SH-SY5Y cells, wild type α-Syn attenuated rotenone and maneb-induced cell death along with an attenuation of toxin-induced mitochondrial membrane potential changes and Reactive Oxygen Species level, whereas the mutant α-Syn constructs exacerbated environmental toxins-induced cytotoxicity. After chronic treatment, wild type α-Syn but not the mutant variants was found to rescue cells from subsequent acute hydrogen peroxide insult. These results suggest that the fundamental property of wild type α-Syn may be protective, and such property may be lost by its familial PD mutations.

Matched MeSH terms: Neurons/drug effects*
Zinc intake during pregnancy increases the proliferation at ventricular zone of the newborn brain

Azman MS, Wan Saudi WS, Ilhami M, Mutalib MS, Rahman MT

Nutr Neurosci, 2009 Feb;12(1):9-12.
PMID: 19178786 DOI: 10.1179/147683009X388904

Neurogenesis involves cell proliferation, cell cycle arrest, differentiation, migration and the natural developmental death of the neural precursors. These processes are highly co-ordinated and governed by cell-cycle genes and neural transcription factors. Zn plays a crucial role as a functional and structural component of enzymes and transcription factors and components of the intracellular signaling pathway associated with the regulation of cell proliferation. The influence of additional Zn intake during pregnancy on the neuronal proliferation at ventricular zone of the developing fetus has been studied. Pups delivered by the group of mice provided with drinking water with 4.0 mM Zn supplement throughout pregnancy contained an increased number of proliferating neurons in the ventricular zone at P0 compared to those delivered by the mice provided with drinking water without any Zn supplement. This finding provides direct evidence to support the notion that maternal Zn levels influence the development of the nervous system of the offspring.

Matched MeSH terms: Neurons/drug effects
Fulltext Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H2S-synthesizing enzymes

Gonzalez-Carter DA, Leo BF, Ruenraroengsak P, Chen S, Goode AE, Theodorou IG, et al.

Sci Rep, 2017 03 02;7:42871.
PMID: 28251989 DOI: 10.1038/srep42871

Silver nanoparticles (AgNP) are known to penetrate into the brain and cause neuronal death. However, there is a paucity in studies examining the effect of AgNP on the resident immune cells of the brain, microglia. Given microglia are implicated in neurodegenerative disorders such as Parkinson's disease (PD), it is important to examine how AgNPs affect microglial inflammation to fully assess AgNP neurotoxicity. In addition, understanding AgNP processing by microglia will allow better prediction of their long term bioreactivity. In the present study, the in vitro uptake and intracellular transformation of citrate-capped AgNPs by microglia, as well as their effects on microglial inflammation and related neurotoxicity were examined. Analytical microscopy demonstrated internalization and dissolution of AgNPs within microglia and formation of non-reactive silver sulphide (Ag2S) on the surface of AgNPs. Furthermore, AgNP-treatment up-regulated microglial expression of the hydrogen sulphide (H2S)-synthesizing enzyme cystathionine-γ-lyase (CSE). In addition, AgNPs showed significant anti-inflammatory effects, reducing lipopolysaccharide (LPS)-stimulated ROS, nitric oxide and TNFα production, which translated into reduced microglial toxicity towards dopaminergic neurons. Hence, the present results indicate that intracellular Ag2S formation, resulting from CSE-mediated H2S production in microglia, sequesters Ag+ ions released from AgNPs, significantly limiting their toxicity, concomitantly reducing microglial inflammation and related neurotoxicity.

Matched MeSH terms: Neurons/drug effects

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