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  1. Fulltext MPTP-induced mouse model of Parkinson's disease: A promising direction of therapeutic strategies
    Mustapha M, Mat Taib CN
    Bosn J Basic Med Sci, 2021 Aug 01;21(4):422-433.
    PMID: 33357211 DOI: 10.17305/bjbms.2020.5181
    Among the popular animal models of Parkinson's disease (PD) commonly used in research are those that employ neurotoxins, especially 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). This neurotoxin exerts it neurotoxicity by causing a barrage of insults, such as oxidative stress, mitochondrial apoptosis, inflammation, excitotoxicity, and formation of inclusion bodies acting singly and in concert, ultimately leading to dopaminergic neuronal damage in the substantia nigra pars compacta and striatum. The selective neurotoxicity induced by MPTP in the nigrostriatal dopaminergic neurons of the mouse brain has led to new perspectives on PD. For decades, the MPTP-induced mouse model of PD has been the gold standard in PD research even though it does not fully recapitulate PD symptomatology, but it does have the advantages of simplicity, practicability, affordability, and fewer ethical considerations and greater clinical correlation than those of other toxin models of PD. The model has rejuvenated PD research and opened new frontiers in the quest for more novel therapeutic and adjuvant agents for PD. Hence, this review summarizes the role of MPTP in producing Parkinson-like symptoms in mice and the experimental role of the MPTP-induced mouse model. We discussed recent developments of more promising PD therapeutics to enrich our existing knowledge about this neurotoxin using this model.
    Matched MeSH terms: Dopaminergic Neurons/drug effects
  2. Fulltext Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer's Disease
    Dhakal S, Kushairi N, Phan CW, Adhikari B, Sabaratnam V, Macreadie I
    Int J Mol Sci, 2019 Oct 14;20(20).
    PMID: 31615073 DOI: 10.3390/ijms20205090
    Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Lewy body dementia, etc. Alzheimer's Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer's Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer's Disease.
    Matched MeSH terms: Neurons/drug effects
  3. 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*
  4. Neurotoxin-Induced Rodent Models of Parkinson's Disease: Benefits and Drawbacks
    El-Gamal M, Salama M, Collins-Praino LE, Baetu I, Fathalla AM, Soliman AM, et al.
    Neurotox Res, 2021 Jun;39(3):897-923.
    PMID: 33765237 DOI: 10.1007/s12640-021-00356-8
    Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by cardinal motor impairments, including akinesia and tremor, as well as by a host of non-motor symptoms, including both autonomic and cognitive dysfunction. PD is associated with a death of nigral dopaminergic neurons, as well as the pathological spread of Lewy bodies, consisting predominantly of the misfolded protein alpha-synuclein. To date, only symptomatic treatments, such as levodopa, are available, and trials aiming to cure the disease, or at least halt its progression, have not been successful. Wong et al. (2019) suggested that the lack of effective therapy against neurodegeneration in PD might be attributed to the fact that the molecular mechanisms standing behind the dopaminergic neuronal vulnerability are still a major scientific challenge. Understanding these molecular mechanisms is critical for developing effective therapy. Thirty-five years ago, Calne and William Langston (1983) raised the question of whether biological or environmental factors precipitate the development of PD. In spite of great advances in technology and medicine, this question still lacks a clear answer. Only 5-15% of PD cases are attributed to a genetic mutation, with the majority of cases classified as idiopathic, which could be linked to exposure to environmental contaminants. Rodent models play a crucial role in understanding the risk factors and pathogenesis of PD. Additionally, well-validated rodent models are critical for driving the preclinical development of clinically translatable treatment options. In this review, we discuss the mechanisms, similarities and differences, as well as advantages and limitations of different neurotoxin-induced rat models of PD. In the second part of this review, we will discuss the potential future of neurotoxin-induced models of PD. Finally, we will briefly demonstrate the crucial role of gene-environment interactions in PD and discuss fusion or dual PD models. We argue that these models have the potential to significantly further our understanding of PD.
    Matched MeSH terms: Dopaminergic Neurons/drug effects
  5. Fulltext 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
  6. Fulltext Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies
    Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Electronic address: andrew.mcintosh@ed.ac.uk, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
    Cell, 2025 Feb 06;188(3):640-652.e9.
    PMID: 39814019 DOI: 10.1016/j.cell.2024.12.002
    In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses. The associations are enriched for antidepressant targets and provide potential repurposing opportunities. Polygenic scores trained using European or multi-ancestry data predicted MD status across all ancestries, explaining up to 5.8% of MD liability variance in Europeans. These findings advance our global understanding of MD and reveal biological targets that may be used to target and develop pharmacotherapies addressing the unmet need for effective treatment.
    Matched MeSH terms: Neurons/drug effects
  7. Fulltext Pluripotent Human embryonic stem cell derived neural lineages for in vitro modelling of enterovirus 71 infection and therapy
    Yap MS, Tang YQ, Yeo Y, Lim WL, Lim LW, Tan KO, et al.
    Virol J, 2016 Jan 06;13:5.
    PMID: 26738773 DOI: 10.1186/s12985-015-0454-6
    The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials.
    Matched MeSH terms: Neurons/drug effects
  8. Quercetin glycosides induced neuroprotection by changes in the gene expression in a cellular model of Parkinson's disease
    Magalingam KB, Radhakrishnan A, Ramdas P, Haleagrahara N
    J Mol Neurosci, 2015 Mar;55(3):609-17.
    PMID: 25129099 DOI: 10.1007/s12031-014-0400-x
    Quercetin glycosides, rutin and isoquercitrin, are potent antioxidants that have been found to possess neuroprotective effect in diseases like Parkinson's and Alzheimer's disease. In the present study, we have examined the gene expression changes with rutin and isoquercitrin pretreatment on 6-hydroxydopamine (6-OHDA)-treated toxicity in rat pheochromocytoma (PC12) cells. PC12 cells were pretreated with rutin or isoquercitrin and subsequently exposed to 6-OHDA. Rutin-pretreated PC12 attenuated the Park2, Park5, Park7, Casp3, and Casp7 genes which were expressed significantly in the 6-OHDA-treated PC12 cells. Rutin upregulated the TH gene which is important in dopamine biosynthesis, but isoquercitrin pretreatment did not affect the expression of this gene. Both rutin and isoquercitrin pretreatments upregulated the ion transport and antiapoptotic genes (NSF and Opa1). The qPCR array data were further validated by qRT-PCR using four primers, Park5, Park7, Casp3, and TH. This finding suggests that changes in the expression levels of transcripts encoded by genes that participate in ubiquitin pathway and dopamine biosynthesis may be involved in Parkinson's disease.
    Matched MeSH terms: Neurons/drug effects*
  9. Fulltext Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring
    Lim WL, Soga T, Parhar IS
    Cell Tissue Res, 2014 Feb;355(2):409-23.
    PMID: 24374911 DOI: 10.1007/s00441-013-1765-9
    The migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the preoptic area (POA) from embryonic day 13 is important for successful reproduction during adulthood. Whether maternal glucocorticoid exposure alters GnRH neuronal morphology and number in the offspring is unknown. This study determines the effect of maternal dexamethasone (DEX) exposure on enhanced green fluorescent protein (EGFP) driven by GnRH promoter neurons (TG-GnRH) in transgenic rats dual-labelled with GnRH immunofluorescence (IF-GnRH). The TG-GnRH neurons were examined in intact male and female rats at different postnatal ages, as a marker for GnRH promoter activity. Pregnant females were subcutaneously injected with DEX (0.1 mg/kg) or vehicle daily during gestation days 13-20 to examine the number of GnRH neurons in P0 male offspring. The total number of TG-GnRH neurons and TG-GnRH/IF-GnRH neuronal ratio increased from P0 and P5 stages to P47-52 stages, suggesting temporal regulation of GnRH promoter activity during postnatal development in intact rats. In DEX-treated P0 males, the number of IF-GnRH neurons decreased within the medial septum, organum vasculosom of the lamina terminalis (OVLT) and anterior hypothalamus. The percentage of TG-GnRH neurons with branched dendritic structures decreased in the OVLT of DEX-P0 males. These results suggest that maternal DEX exposure affects the number and dendritic development of early postnatal GnRH neurons in the OVLT/POA, which may lead to altered reproductive functions in adults.
    Matched MeSH terms: Neurons/drug effects
  10. Habenular Kiss1 neurons modulate the serotonergic system in the brain of zebrafish
    Ogawa S, Ng KW, Ramadasan PN, Nathan FM, Parhar IS
    Endocrinology, 2012 May;153(5):2398-407.
    PMID: 22454151 DOI: 10.1210/en.2012-1062
    The Kiss1/KISS1 gene has recently been implicated as a potent hypothalamic regulator of reproductive functions, in particular, the onset of puberty in mammals. In zebrafish (Danio rerio), there are two kiss1 homologues (kiss1 and kiss2) expressed in the brain: Kiss2-expressing neurons in the hypothalamic nuclei are considered potent regulators of reproduction, whereas the role of Kiss1-expressing neurons in the habenula remains unknown. We first analyzed the expression of kiss1 mRNA in a transgenic zebrafish, in which the habenula-interpeduncular nucleus (IPN) pathway is labelled with green fluorescent protein, and our application of a biocytin neural tracer into the habenula showed the presence of neuronal projections of Kiss1 neurons to the ventral IPN. Therefore, we speculated that kiss1 neurons might regulate the serotonergic system in the raphe. However, laser microdissection followed by real-time PCR revealed the expression of Kiss1 receptor (kissr1) mRNA in the habenula and the ventral IPN but not in the dorsal IPN or the serotonergic neurons in the raphe nuclei. Dual-fluorescent in situ hybridization revealed the coexpression of kiss1 and kissr1 mRNA in the habenula. Administration of Kiss1 significantly decreased the level of kiss1 mRNA (0.3- to 0.5-fold, P < 0.001), but the level of c-fos mRNA was increased (≈ 3-fold, P < 0.05) in the ventral habenula, suggesting that there is autocrine regulation of the kiss1 gene. Kiss1 administration significantly increased the c-fos mRNA levels in the raphe nuclei (2.5-fold, P < 0.001) and genes involved in the regulation of serotonin levels (pet1 and slc6a4a; 3.3- and 2.2-fold, P < 0.01). These findings suggest that the autocrine-regulated habenular Kiss1 neurons indirectly regulate the serotonergic system in the raphe nuclei through the IPN in the zebrafish.
    Matched MeSH terms: Serotonergic Neurons/drug effects
  11. Amperometric microbiosensor as an alternative tool for investigation of D-serine in brain
    Mohd Zain Z, Ab Ghani S, O'Neill RD
    Amino Acids, 2012 Nov;43(5):1887-94.
    PMID: 22865247 DOI: 10.1007/s00726-012-1365-0
    This paper discusses the application of a reagentless, selective microbiosensor as a useful alternative tool for monitoring D-serine in neural samples. The main components of the 125-μm-diameter disk biosensor were D-amino acid oxidase for D-serine sensitivity (linear region slope, 61 ± 7 μA cm(-2) mM(-1); limit of detection, 20 nM), and poly-phenylenediamine for rejection of electroactive interference. The response time of the biosensor was of the order of 1 s, ideal for 'real-time' monitoring, and detection of systemically administered D-serine in brain extracellular fluid is demonstrated. Exploitation of this probe might resolve queries involving regulation of D-serine in excitotoxicity, and modulation of N-methyl-D-aspartate receptor function by D-serine and glycine in the central nervous system.
    Matched MeSH terms: Neurons/drug effects*
  12. 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*
  13. Gabapentin completely attenuated the acute morphine-induced c-Fos expression in the rat nucleus accumbens
    Kazi JA, Abu-Hassan MI
    J Mol Neurosci, 2011 Oct;45(2):101-9.
    PMID: 20734160 DOI: 10.1007/s12031-010-9435-9
    A growing body of evidence suggests the existence of a functional interaction between gabapentin (GBP)-morphine system. However, the neuro-anatomical sites and molecular mechanism of action of gabapentin-morphine interaction to prevent and reverse morphine side effects as well as enhancement of the analgesic effect of morphine is not clear. Therefore, we examined the combined effects of GBP-morphine on acute morphine-induced c-Fos expression in rat nucleus accumbens. The combined effect of GBP-morphine was examined by means of c-Fos immunohistochemistry. A single intraperitoneal injection (i.p.) of morphine (10 mg/kg), saline (control), and co-injection of GBP (150 mg/kg) with morphine (5 mg/kg) was administered under anesthesia. The deeply anesthetized rats were perfused transcardially with 4% paraformaldehyde 2 h after drugs administration. Serial 40 μm thick sections of brain were cut and processed by immunohistochemistry to locate and quantify the sites and number of neurons with c-Fos immunoreactivity. Detection of c-Fos protein was performed using the peroxidase-antiperoxidase detection protocol. The present study demonstrated that, administration of GBP (150 mg/kg, i.p.) in combination with morphine (5 mg/kg, i.p.) significantly (p < 0.01) attenuated the acute morphine (5 mg/kg, i.p.)-induced c-Fos expression in the rat nucleus accumbens shell. Present results showed that GBP-morphine combination action prevented the acute morphine-induced c-Fos expression in rat nucleus accumbens. Moreover, this study provides first evidence of neuro-anatomical site and that GBP neutralized the morphine-induced activation of rat nucleus accumbens shell.
    Matched MeSH terms: Neurons/drug effects
  14. Nitric oxide (NO), citrulline-NO cycle enzymes, glutamine synthetase, and oxidative status in kainic acid-mediated excitotoxicity in rat brain
    Swamy M, Sirajudeen KN, Chandran G
    Drug Chem Toxicol, 2009;32(4):326-31.
    PMID: 19793024 DOI: 10.1080/01480540903130641
    Neuronal excitation, involving the excitatory glutamate receptors, is recognized as an important underlying mechanism in neurodegenerative disorders. To understand their role in excitotoxicity, the nitric oxide synthase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite, thiobarbituric acid-reactive substances (TBARS), and total antioxidant status (TAS), were estimated in the cerebral cortex, cerebellum, and brain stem of rats subjected to kainic acid-mediated excitotoxicity. The results of this study clearly demonstrated the increased production of NO by increased activity of NOS. The increased activities of AS and AL suggest the increased and effective recycling of citrulline to arginine in excitotoxicity, making NO production more effective and contributing to its toxic effects. The decreased activity of GS may favor the prolonged availability of glutamic acid, causing excitotoxicity, leading to neuronal damage. The increased formation of TBARS and decreased TAS indicate the presence of oxidative stress in excitotoxicity.
    Matched MeSH terms: Neurons/drug effects*
  15. Role of supraspinal vasopressin neurones in the effects of atrial natriuretic peptide on sympathetic nerve activity
    Yusof AP, Yusoff NH, Suhaimi FW, Coote JH
    Auton Neurosci, 2009 Jun 15;148(1-2):50-4.
    PMID: 19349212 DOI: 10.1016/j.autneu.2009.03.005
    The aim of the present study was to determine if paraventricular-spinal vasopressin neurones participate in the sympatho-inhibitory effects of systemically administered atrial natriuretic peptide (ANP) on renal sympathetic nerve activity (RSNA). Experiments were carried out on male Sprague-Dawley rats anesthetized with 1.3 g/kg urethane. Changes in mean arterial pressure (mm Hg), heart rate (beats per minute) and RSNA (%) were measured following intravenous bolus administration of ANP (250 ng, 500 ng and 5 microg). Intrathecal application of selective V 1a receptor antagonist was performed to test for the involvement of supraspinal vasopressin pathways in mediating the effect on sympathetic outflow evoked by intravenous ANP administration. The results obtained demonstrated that both low and high doses of ANP caused renal sympathoinhibition (250 ng; - 7.5 +/- 1%, 500 ng; - 14.2 +/- 1%, 5 microg; - 16.4 +/- 2%), concomitant with vasodilation and bradycardia. After spinal vasopressin receptor blockade, the inhibitory effects of ANP were prevented and there was a small renal sympatho-excitation (250 ng; + 1.7 +/- 0.2%, 500 ng; + 6.1 +/- 0.03%, 5 microg; + 8.0 +/- 0.03%, P < 0.05). Therefore, the renal sympathetic nerve inhibition elicited by circulating ANP is dependent on the efficacy of a well established supraspinal vasopressin pathway. Since supraspinal vasopressin neurones without exception excite renal sympathetic neurones, it is suggested that ANP elicits this effect by activating cardiac vagal afferents that inhibit the spinally projecting vasopressin neurones at their origin in the paraventricular nucleus of the hypothalamus.
    Matched MeSH terms: Neurons/drug effects
  16. Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum
    Haleagrahara N, Siew CJ, Mitra NK, Kumari M
    Neurosci Lett, 2011 Aug 15;500(2):139-43.
    PMID: 21704673 DOI: 10.1016/j.neulet.2011.06.021
    An increasing large body of research on Parkinson's disease (PD) has focused on the understanding of the mechanisms behind the potential neuro protection offered by antioxidants and iron chelating agents. In this study, the protective effect of the bioflavonoid quercetin on 6-hydroxydopamine (6-OHDA)-induced model of PD was investigated. PD was induced by a single intracisternal injection of 6-hydroxydopamine (300μg) to male Sprague-Dawley rats. Quercetin treatment (30mg/kg body weight) over 14 consecutive days markedly increased the striatal dopamine and antioxidant enzyme levels compared with similar measurements in the group treated with 6-OHDA alone. There was a significant decrease in protein carbonyl content in the striatum compared with that of rats that did not receive quercetin. A significant increase in neuronal survivability was also found with quercetin treatment in rats administered 6-OHDA. In conclusion, treatment with quercetin defended against the oxidative stress in the striatum and reduced the dopaminergic neuronal loss in the rat model of PD.
    Matched MeSH terms: Neurons/drug effects
  17. Fulltext Prospective role of mitochondrial apoptotic pathway in mediating GMG-ITC to reduce cytotoxicity in H2O2-induced oxidative stress in differentiated SH-SY5Y cells
    Jaafaru MS, Nordin N, Rosli R, Shaari K, Bako HY, Noor NM, et al.
    Biomed Pharmacother, 2019 Nov;119:109445.
    PMID: 31541852 DOI: 10.1016/j.biopha.2019.109445
    The antioxidant and neuroprotective activity of Glucomoringin isothiocyanate (GMG-ITC) have been reported in in vivo and in vitro models of neurodegenerative diseases. However, its neuroprotective role via mitochondrial-dependent pathway in a noxious environment remains unknown. The main objective of the present study was to unveil the mitochondrial apoptotic genes' profile and prospectively link with neuroprotective activity of GMG-ITC through its ROS scavenging. The results showed that pre-treatment of differentiated SH-SY5Y cells with 1.25 μg/mL purified isolated GMG-ITC, significantly reduced reactive oxygen species (ROS) production level, compared to H2O2 control group, as evidenced by flow cytometry-based evaluation of ROS generation. Presence of GMG-ITC prior to development of oxidative stress condition, downregulated the expression of cyt-c, p53, Apaf-1, Bax, CASP3, CASP8 and CASP9 genes with concurrent upregulation of Bcl-2 gene in mitochondrial apoptotic signalling pathway. Protein Multiplex revealed significant decreased in cyt-c, p53, Apaf-1, Bax, CASP8 and CASP9 due to GMG-ITC pre-treatment in oxidative stress condition. The present findings speculated that pre-treatment with GMG-ITC may alleviate oxidative stress condition in neuronal cells by reducing ROS production level and protect the cells against apoptosis via neurodegenerative disease potential pathways.
    Matched MeSH terms: Neurons/drug effects
  18. 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
  19. 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
  20. Therapeutic potential of neurogenesis and melatonin regulation in Alzheimer's disease
    Mihardja M, Roy J, Wong KY, Aquili L, Heng BC, Chan YS, et al.
    Ann N Y Acad Sci, 2020 10;1478(1):43-62.
    PMID: 32700392 DOI: 10.1111/nyas.14436
    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the hallmark pathologies of amyloid-beta plaques and neurofibrillary tangles. Symptoms of this devastating disease include behavioral changes and deterioration of higher cognitive functions. Impairment of neurogenesis has also been shown to occur in AD, which adversely impacts new neuronal cell growth, differentiation, and survival. This impairment possibly results from the cumulative effects of the various pathologies of AD. Preclinical studies have suggested that the administration of melatonin-the pineal hormone primarily responsible for the regulation of the circadian rhythm-targets the effects of AD pathologies and improves cognitive impairment. It is postulated that by mitigating the effect of these pathologies, melatonin can also rescue neurogenesis impairment. This review aims to explore the effect of AD pathologies on neurogenesis, as well as the mechanisms by which melatonin is able to ameliorate AD pathologies to potentially promote neurogenesis.
    Matched MeSH terms: Neurons/drug effects
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