Displaying publications 1 - 20 of 160 in total

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  1. Mani V, Parle M, Ramasamy K, Abdul Majeed AB
    J Sci Food Agric, 2011 Jan 15;91(1):186-92.
    PMID: 20848667 DOI: 10.1002/jsfa.4171
    Coriandrum sativum L., commonly known as coriander and belonging to the family Apiaceae (Umbelliferae), is cultivated throughout the world for its nutritional value. The present study was undertaken to investigate the effects of fresh Coriandrum sativum leaves (CSL) on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. In this study, CSL (5, 10 and 15% w/w of diet) was fed orally with a specially prepared diet for 45 days consecutively to experimental animals. Elevated plus-maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam, scopolamine and ageing-induced amnesia served as the interoceptive behavioral models.
    Matched MeSH terms: Brain/metabolism
  2. Ismail N, Ismail M, Azmi NH, Bakar MFA, Yida Z, Stanslas J, et al.
    Chem Biol Interact, 2017 Sep 25;275:61-73.
    PMID: 28734741 DOI: 10.1016/j.cbi.2017.07.014
    The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble β-amyloid (Aβ) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE). The TQRF and TQ conventional emulsions (CE), named as TQRFCE and TQCE, respectively were studied for comparison. Statin (simvastatin) and non-statin (probucol) cholesterol-lowering agents, and a mild-to-severe Alzheimer's disease drug (donepezil) were served as control drugs. The Sprague Dawley rats were fed with HFCD for 6 months, and treated with the intervention groups via oral gavage daily for the last 3 months. As a result, HFCD-fed rats exhibited hypercholesterolaemia, accompanied by memory deficit, increment of lipid peroxidation and soluble Aβ levels, decrement of total antioxidant status and down-regulation of antioxidants genes expression levels. TQRFNE demonstrated comparable effects to the other intervention groups and control drugs in serum biomarkers as well as in the learning and memory test. Somehow, TQRFNE was more prominent than those intervention groups and control drugs in brain biomarkers concomitant to gene and protein expression levels. Supplementation of TQRFNE into an HFCD thus could ameliorate memory deficit, lipid peroxidation and soluble Aβ levels as well as improving the total antioxidant status and antioxidants genes expression levels.
    Matched MeSH terms: Brain/metabolism
  3. Ilyas S, Tabasum R, Iftikhar A, Nazir M, Hussain A, Hussain A, et al.
    Sci Rep, 2021 01 18;11(1):1708.
    PMID: 33462261 DOI: 10.1038/s41598-020-80579-5
    Ifosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors. However, nephro, hepato, neuro cardio, and hematological toxicities associated with ifosfamide render its use limited. These side effects could range from organ failure to life-threatening situations. The present study aimed to evaluate the attenuating efficiency of Berberis vulgaris root extract (BvRE), a potent nephroprotective, hepatoprotective, and lipid-lowering agent, against ifosfamide-induced toxicities. The study design comprised eight groups of Swiss albino rats to assess different dose regimes of BvRE and ifosfamide. Biochemical analysis of serum (serum albumin, blood urea nitrogen, creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, and triglycerides) along with complete blood count was performed. Kidney, liver, brain, and heart tissue homogenates were used to find malondialdehyde, catalase, and glutathione S-transferase levels in addition to the acetylcholinesterase of brain tissue. The results were further validated with the help of the histopathology of the selected organs. HeLa cells were used to assess the effect of BvRE on ifosfamide cytotoxicity in MTT assay. The results revealed that pre- and post-treatment regimens of BvRE, as well as the combination therapy exhibited marked protective effects against ifosfamide-induced nephro, hepato, neuro, and cardiotoxicity. Moreover, ifosfamide depicted a synergistic in vitro cytotoxic effect on HeLa cells in the presence of BvRE. These results corroborate that the combination therapy of ifosfamide with BvRE in cancer treatment can potentiate the anticancer effects of ifosfamide along with the amelioration of its conspicuous side effects.
    Matched MeSH terms: Brain/metabolism
  4. Tamijani SM, Karimi B, Amini E, Golpich M, Dargahi L, Ali RA, et al.
    Seizure, 2015 Sep;31:155-64.
    PMID: 26362394 DOI: 10.1016/j.seizure.2015.07.021
    Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here.
    Matched MeSH terms: Brain/metabolism
  5. Raman S, Mahmood S, Hilles AR, Javed MN, Azmana M, Al-Japairai KAS
    Curr Drug Metab, 2020;21(9):649-660.
    PMID: 32384025 DOI: 10.2174/1389200221666200508074348
    BACKGROUND: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery.

    METHODS: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs.

    RESULTS: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain.

    CONCLUSION: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

    Matched MeSH terms: Brain/metabolism*
  6. Jafarieh O, Md S, Ali M, Baboota S, Sahni JK, Kumari B, et al.
    Drug Dev Ind Pharm, 2015;41(10):1674-81.
    PMID: 25496439 DOI: 10.3109/03639045.2014.991400
    Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra.
    Matched MeSH terms: Brain/metabolism
  7. Kumar MR, Yeap SK, Mohamad NE, Abdullah JO, Masarudin MJ, Khalid M, et al.
    BMC Complement Med Ther, 2021 Jul 01;21(1):183.
    PMID: 34210310 DOI: 10.1186/s12906-021-03358-3
    BACKGROUND: In recent years, researchers are interested in the discovery of active compounds from traditional remedies and natural sources, as they reveal higher therapeutic efficacies and improved toxicological profiles. Among the various traditional treatments that have been widely studied and explored for their potential therapeutic benefits, kefir, a fermented beverage, demonstrates a broad spectrum of pharmacological properties, including antioxidant, anti-inflammation, and healing activities. These health-promoting properties of kefir vary among the kefir cultures found at the different part of the world as different media and culture conditions are used for kefir maintenance and fermentation.

    METHODS: This study investigated the microbial composition and readily found bioactive compounds in water kefir fermented in Malaysia using 16S rRNA microbiome and UHPLC sequencing approaches. The toxicity effects of the kefir water administration in BALB/c mice were analysed based on the mice survival, body weight index, biochemistry profile, and histopathological changes. The antioxidant activities were evaluated using SOD, FRAP, and NO assays.

    RESULTS: The 16S rRNA amplicon sequencing revealed the most abundant species found in the water kefir was Lactobacillus hilgardii followed by Lactobacillus harbinensis, Acetobacter lovaniensis, Lactobacillus satsumensis, Acetobacter tropicalis, Lactobacillus zeae, and Oenococcus oeni. The UHPLC screening showed flavonoid and phenolic acid derivatives as the most important bioactive compounds present in kefir water which has been responsible for its antioxidant activities. Subchronic toxicity study showed no toxicological signs, behavioural changes, or adverse effects by administrating 10 mL/kg/day and 2.5 mL/kg/day kefir water to the mice. Antioxidants assays demonstrated enhanced SOD and FRAP activities and reduced NO level, especially in the brain and kidney samples.

    CONCLUSIONS: This study will help to intensify the knowledge on the water kefir microbial composition, available phytochemicals and its toxicological and antioxidant effects on BALB/c mice since there are very limited studies on the water kefir grain fermented in Malaysia.

    Matched MeSH terms: Brain/metabolism
  8. Au A
    Adv Clin Chem, 2018 03 08;85:31-69.
    PMID: 29655461 DOI: 10.1016/bs.acc.2018.02.002
    Ischemic stroke is a sudden loss of brain function due to the reduction of blood flow. Brain tissues cease to function with subsequent activation of the ischemic cascade. Metabolomics and lipidomics are modern disciplines that characterize the metabolites and lipid components of a biological system, respectively. Because the pathogenesis of ischemic stroke is heterogeneous and multifactorial, it is crucial to establish comprehensive metabolomic and lipidomic approaches to elucidate these alterations in this disease. Fortunately, metabolomic and lipidomic studies have the distinct advantages of identifying tissue/mechanism-specific biomarkers, predicting treatment and clinical outcome, and improving our understanding of the pathophysiologic basis of disease states. Therefore, recent applications of these analytical approaches in the early diagnosis of ischemic stroke were discussed. In addition, the emerging roles of metabolomics and lipidomics on ischemic stroke were summarized, in order to gain new insights into the mechanisms underlying ischemic stroke and in the search for novel metabolite biomarkers and their related pathways.
    Matched MeSH terms: Brain/metabolism*
  9. Zulkifli I, Akmal AF, Soleimani AF, Hossain MA, Awad EA
    Poult Sci, 2018 Apr 01;97(4):1306-1314.
    PMID: 29381776 DOI: 10.3382/ps/pex436
    A study with a 4 × 2 factorial arrangement was conducted to investigate the effects of 4 dietary protein levels and 2 environmental conditions on acute phase proteins (APP), brain heat shock protein (HSP) 70 density, and growth performance of broiler chickens. Day-old broiler chicks (Cobb 500) were fed isocaloric diets but with various levels of crude protein (CP), namely, (1) 21.0 and 19.0% CP in starter and finisher diets, respectively (control), (2) 19.5 and 17.5% CP in starter and finisher diets, respectively (Diet A), (3) 18.0 and 16.0% CP in starter and finisher diets, respectively (Diet B), and (4) 16.5 and 14.5% CP in starter and finisher diets, respectively (Diet C). Equal numbers of birds from each diet were subjected to either 23±1°C throughout or 33±1°C for 6 h per d from 22 to 35 d of age. From d 1 to 21, feed intake (FI) and weight gain (WG) decreased linearly (P = 0.021 and P = 0.009, respectively), as CP level was reduced. During the heat treatment period (d 22 to 35), there were significant (P = 0.04) diet × heat treatment interactions for FCR. Diet had no effect on FCR among the unheated birds, but the ratio increased linearly (P = 0.007) as dietary CP level decreased. Irrespective of ambient temperature, there was a significant linear decrease in FI (P = 0.032) and WG (P < 0.001) as dietary CP level decreased. Low-CP diets improved the survivability of heat-stressed broilers when compared to those fed control diets. Low-CP diets linearly decreased (P < 0.01) APP (ovotransferrin and alpha-acid glycoprotein) responses. Both APP and HSP 70 reactions were elevated following heat treatment. In conclusion, feeding broilers with low-CP diets adversely affect the growth performance of broilers under heat stress condition. However, low-CP diets were beneficial in improving the survivability. Because APP are involved in the restoration of homeostasis, the adverse effect of low-CP diet on the synthesis of these proteins could be of concern.
    Matched MeSH terms: Brain/metabolism
  10. Safdar A, Zakaria R, Aziz CBA, Rashid U, Azman KF
    Biogerontology, 2020 04;21(2):203-216.
    PMID: 31792648 DOI: 10.1007/s10522-019-09854-x
    One of the most significant hallmarks of aging is cognitive decline. D-galactose administration may impair memory and mimic the effects of natural aging. In this study, the efficiency of goat milk to protect against memory decline was tested. Fifty-two male Sprague-Dawley rats were randomly divided into four groups: (i) control group, (ii) goat milk treated group, (iii) D-galactose treated group, and (iv) goat milk plus D-galactose treated group. Subcutaneous injections of D-galactose at 120 mg/kg and oral administrations of goat milk at 1 g/kg were chosen for the study. Goat milk and D-galactose were administered concomitantly for 6 weeks, while the control group received saline. After 6 weeks, novel object recognition and T-maze tests were performed to evaluate memory of rats. Following behavioral tests, the animals were sacrificed, and right brain homogenates were analyzed for levels of lipid peroxidation, antioxidant enzymes and neurotrophic factors. The left brain hemisphere was used for histological study of prefrontal cortex and hippocampus. There was a significant memory impairment, an increase in oxidative stress and neurodegeneration and a reduction in antioxidant enzymes and neurotrophic factors levels in the brain of D-galactose treated rats compared to controls. Goat milk treatment attenuated memory impairment induced by D-galactose via suppressing oxidative stress and neuronal damage and increasing neurotrophic factors levels, thereby suggesting its potential role as a geroprotective food.
    Matched MeSH terms: Brain/metabolism*
  11. Suliman NA, Taib CNM, Moklas MAM, Basir R
    Neurotox Res, 2018 02;33(2):402-411.
    PMID: 28933048 DOI: 10.1007/s12640-017-9806-x
    Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory. This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆9-THC) in cognitive performance that influenced by the neurogenesis. Different doses of ∆9-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured. Throughout this study, ∆9-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective. Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.
    Matched MeSH terms: Brain/metabolism
  12. Tan SL, Stanslas J, Basri M, Abedi Karjiban RA, Kirby BP, Sani D, et al.
    Curr Drug Deliv, 2015;12(6):795-804.
    PMID: 26324229
    Carbamzepine (CBZ) was encapsulated in a parenteral oil-in-water nanoemulsion, in an attempt to improve its bioavailability. The particle size, polydispersity index and zeta potential were measured using dynamic light scattering. Other parameters such as pH, osmolality, viscosity, drug loading efficiency and entrapment efficiency were also recorded. Transmission electron microscopy revealed that emulsion droplets were almost spherical in shape and in the nano-range. The in vitro release profile was best characterized by Higuchi's equation. The parenteral nanoemulsion of CBZ showed significantly higher AUC0→5, AUC0→∞, AUMC0→5, AUMC0→∞, Cmax and lower clearance than that of CBZ solution in plasma. Additionally, parenteral nanoemulsion of CBZ showed significantly higher AUC0→∞, AUMC0→∞ and Cmaxthan that of CBZ solution in brain. The parenteral nanoemulsion of CBZ could therefore use as a carrier, worth exploring further for brain targeting.
    Matched MeSH terms: Brain/metabolism
  13. Perumal R, Bhattathiry EP
    Med J Malaya, 1970 Mar;24(3):208-11.
    PMID: 4246803
    Matched MeSH terms: Brain/metabolism
  14. Tee HK, Tan CW, Yogarajah T, Lee MHP, Chai HJ, Hanapi NA, et al.
    PLoS Pathog, 2019 11;15(11):e1007863.
    PMID: 31730673 DOI: 10.1371/journal.ppat.1007863
    Enterovirus A71 (EV-A71) causes hand, foot and mouth disease epidemics with neurological complications and fatalities. However, the neuropathogenesis of EV-A71 remains poorly understood. In mice, adaptation and virulence determinants have been mapped to mutations at VP2-149, VP1-145 and VP1-244. We investigate how these amino acids alter heparin-binding phenotype and shapes EV-A71 virulence in one-day old mice. We constructed six viruses with varying residues at VP1-98, VP1-145 (which are both heparin-binding determinants) and VP2-149 (based on the wild type 149K/98E/145Q, termed KEQ) to generate KKQ, KKE, KEE, IEE and IEQ variants. We demonstrated that the weak heparin-binder IEE was highly lethal in mice. The initially strong heparin-binding IEQ variant acquired an additional mutation VP1-K244E, which confers weak heparin-binding phenotype resulting in elevated viremia and increased virus antigens in mice brain, with subsequent high virulence. IEE and IEQ-244E variants inoculated into mice disseminated efficiently and displayed high viremia. Increasing polymerase fidelity and impairing recombination of IEQ attenuated the virulence, suggesting the importance of population diversity in EV-A71 pathogenesis in vivo. Combining in silico docking and deep sequencing approaches, we inferred that virus population diversity is shaped by electrostatic interactions at the five-fold axis of the virus surface. Electrostatic surface charges facilitate virus adaptation by generating poor heparin-binding variants for better in vivo dissemination in mice, likely due to reduced adsorption to heparin-rich peripheral tissues, which ultimately results in increased neurovirulence. The dynamic switching between heparin-binding and weak heparin-binding phenotype in vivo explained the neurovirulence of EV-A71.
    Matched MeSH terms: Brain/metabolism
  15. 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: Brain/metabolism
  16. Dutta S, Rahman S, Ahmad R, Kumar T, Dutta G, Banerjee S, et al.
    Expert Rev Neurother, 2021 12;21(12):1455-1472.
    PMID: 34756134 DOI: 10.1080/14737175.2021.2003705
    INTRODUCTION: Dementia is a progressive neurodegenerative disorder impairing memory and cognition. Alzheimer's Disease, followed by vascular dementia - the most typical form. Risk factors for vascular dementia include diabetes, cardiovascular disease, hyperlipidemia. Lipids' levels are significantly associated with vascular changes in the brain.

    AREAS COVERED: The present article reviews the cholesterol metabolism in the brain, which includes: the synthesis, transport, storage, and elimination process. Additionally, it reviews the role of cholesterol in the pathogenesis of dementia and statin as a therapeutic intervention in dementia. In addition to the above, it further reviews evidence in support of as well as against statin therapy in dementia, recent updates of statin pharmacology, and demerits of use of statin pharmacotherapy.

    EXPERT OPINION: Amyloid-β peptides and intraneuronal neurofibrillary tangles are markers of Alzheimer's disease. Evidence shows cholesterol modulates the functioning of enzymes associated with Amyloid-β peptide processing and synthesis. Lowering cholesterol using statin may help prevent or delay the progression of dementia. This paper reviews the role of statin in dementia and recommends extensive future studies, including genetic research, to obtain a precise medication approach for patients with dementia.

    Matched MeSH terms: Brain/metabolism
  17. Seth EA, Lee HC, Yusof HHBM, Nordin N, Cheah YK, Ho ETW, et al.
    PLoS One, 2020;15(7):e0236826.
    PMID: 32730314 DOI: 10.1371/journal.pone.0236826
    Down syndrome (DS), is the most common cause of intellectual disability, and is characterized by defective neurogenesis during perinatal development. To identify metabolic aberrations in early neurogenesis, we profiled neurospheres derived from the embryonic brain of Ts1Cje, a mouse model of Down syndrome. High-throughput phenotypic microarray revealed a significant decrease in utilisation of 17 out of 367 substrates and significantly higher utilisation of 6 substrates in the Ts1Cje neurospheres compared to controls. Specifically, Ts1Cje neurospheres were less efficient in the utilisation of glucose-6-phosphate suggesting a dysregulation in the energy-producing pathway. T Cje neurospheres were significantly smaller in diameter than the controls. Subsequent preliminary study on supplementation with 6-phosphogluconic acid, an intermediate of glucose-6-phosphate metabolism, was able to rescue the Ts1Cje neurosphere size. This study confirmed the perturbed pentose phosphate pathway, contributing to defects observed in Ts1Cje neurospheres. We show for the first time that this comprehensive energetic assay platform facilitates the metabolic characterisation of Ts1Cje cells and confirmed their distinguishable metabolic profiles compared to the controls.
    Matched MeSH terms: Brain/metabolism
  18. Ip YK, Leong MW, Sim MY, Goh GS, Wong WP, Chew SF
    J Exp Biol, 2005 May;208(Pt 10):1993-2004.
    PMID: 15879078
    The objective of this study was to elucidate if chronic and acute ammonia intoxication in mudskippers, Periophthalmodon schlosseri and Boleophthalmus boddaerti, were associated with high levels of ammonia and/or glutamine in their brains, and if acute ammonia intoxication could be prevented by the administration of methionine sulfoximine [MSO; an inhibitor of glutamine synthetase (GS)] or MK801 [an antagonist of N-methyl D-aspartate type glutamate (NMDA) receptors]. For P. schlosseri and B. boddaerti exposed to sublethal concentrations (100 and 8 mmol l(-1) NH4Cl, respectively, at pH 7.0) of environmental ammonia for 4 days, brain ammonia contents increased drastically during the first 24 h, and they reached 18 and 14.5 micromol g(-1), respectively, at hour 96. Simultaneously, there were increases in brain glutamine contents, but brain glutamate contents were unchanged. Because glutamine accumulated to exceptionally high levels in brains of P. schlosseri (29.8 micromol g(-1)) and B. boddaerti (12.1 micromol g(-1)) without causing death, it can be concluded that these two mudskippers could ameliorate those problems associated with glutamine synthesis and accumulation as observed in patients suffering from hyperammonemia. P. schlosseri and B. boddaerti could tolerate high doses of ammonium acetate (CH3COONH4) injected into their peritoneal cavities, with 24 h LC50 of 15.6 and 12.3 micromol g(-1) fish, respectively. After the injection with a sublethal dose of CH3COONH4 (8 micromol g(-1) fish), there were significant increases in ammonia (5.11 and 8.36 micromol g(-1), respectively) and glutamine (4.22 and 3.54 micromol g(-1), respectively) levels in their brains at hour 0.5, but these levels returned to normal at hour 24. By contrast, for P. schlosseri and B. boddaerti that succumbed within 15-50 min to a dose of CH3COONH4 (15 and 12 micromol g(-1) fish, respectively) close to the LC50 values, the ammonia contents in the brains reached much higher levels (12.8 and 14.9 micromol g(-1), respectively), while the glutamine level remained relatively low (3.93 and 2.67 micromol g(-1), respectively). Thus, glutamine synthesis and accumulation in the brain was not the major cause of death in these two mudskippers confronted with acute ammonia toxicity. Indeed, MSO, at a dosage (100 microg g(-1) fish) protective for rats, did not protect B. boddaerti against acute ammonia toxicity, although it was an inhibitor of GS activities from the brains of both mudskippers. In the case of P. schlosseri, MSO only prolonged the time to death but did not reduce the mortality rate (100%). In addition, MK801 (2 microg g(-1) fish) had no protective effect on P. schlosseri and B. boddaerti injected with a lethal dose of CH3COONH4, indicating that activation of NMDA receptors was not the major cause of death during acute ammonia intoxication. Thus, it can be concluded that there are major differences in mechanisms of chronic and acute ammonia toxicity between brains of these two mudskippers and mammalian brains.
    Matched MeSH terms: Brain/metabolism*
  19. Ip YK, Lim CK, Lee SL, Wong WP, Chew SF
    J Exp Biol, 2004 Aug;207(Pt 17):3015-23.
    PMID: 15277556
    The objective of this study was to determine the effects of feeding on the excretory nitrogen (N) metabolism of the giant mudskipper, Periophthalmodon schlosseri, with special emphasis on the role of urea synthesis in ammonia detoxification. The ammonia and urea excretion rates of P. schlosseri increased 1.70- and 1.92-fold, respectively, within the first 3 h after feeding on guppies. Simultaneously, there were significant decreases in ammonia levels in the plasma and the brain, and in urea contents in the muscle and liver, of P. schlosseri at 3 h post-feeding. Thus, it can be concluded that P. schlosseri was capable of unloading ammonia originally present in some of its tissues in anticipation of ammonia released from the catabolism of excess amino acids after feeding. Subsequently, there were significant increases in urea content in the muscle, liver and plasma (1.39-, 2.17- and 1.62-fold, respectively) at 6 h post-feeding, and the rate of urea synthesis apparently increased 5.8-fold between 3 h and 6 h. Increased urea synthesis might have occurred in the liver of P. schlosseri because the greatest increase in urea content was observed therein. The excess urea accumulated in the body at 6 h was completely excreted between 6 and 12 h, and the percentage of waste-N excreted as urea-N increased significantly to 26% during this period, but never exceeded 50%, the criterion for ureotely, meaning that P. schlosseri remained ammonotelic after feeding. By 24 h, 62.7% of the N ingested by P. schlosseri was excreted, out of which 22.6% was excreted as urea-N. This is the first report on the involvement of increased urea synthesis and excretion in defense against ammonia toxicity in the giant mudskipper, and our results suggest that an ample supply of energy resources, e.g. after feeding, is a prerequisite for the induction of urea synthesis. Together, increases in nitrogenous excretion and urea synthesis after feeding effectively prevented a postprandial surge of ammonia in the plasma of P. schlosseri as reported previously for other fish species. Consequently, contrary to previous reports, there were significant decreases in the ammonia content of the brain of P. schlosseri throughout the 24 h period post-feeding, accompanied by a significant decrease in brain glutamine content between 12 h and 24 h.
    Matched MeSH terms: Brain/metabolism
  20. Sakharkar MK, Kashmir Singh SK, Rajamanickam K, Mohamed Essa M, Yang J, Chidambaram SB
    PLoS One, 2019;14(9):e0220995.
    PMID: 31487305 DOI: 10.1371/journal.pone.0220995
    Parkinson's disease (PD) is an irreversible and incurable multigenic neurodegenerative disorder. It involves progressive loss of mid brain dopaminergic neurons in the substantia nigra pars compacta (SN). We compared brain gene expression profiles with those from the peripheral blood cells of a separate sample of PD patients to identify disease-associated genes. Here, we demonstrate the use of gene expression profiling of brain and blood for detecting valid targets and identifying early PD biomarkers. Implementing this systematic approach, we discovered putative PD risk genes in brain, delineated biological processes and molecular functions that may be particularly disrupted in PD and also identified several putative PD biomarkers in blood. 20 of the differentially expressed genes in SN were also found to be differentially expressed in the blood. Further application of this methodology to other brain regions and neurological disorders should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for PD. The identification of valid peripheral biomarkers for PD may ultimately facilitate early identification, intervention, and prevention efforts as well.
    Matched MeSH terms: Brain/metabolism
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