Displaying publications 1 - 20 of 64 in total

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  1. High Melatonin Conditions by Constant Darkness and High Temperature Differently Affect Melatonin Receptor mt1 and TREK Channel trek2a in the Brain of Zebrafish
    Loganathan K, Moriya S, Parhar IS
    Zebrafish, 2018 10;15(5):473-483.
    PMID: 30102584 DOI: 10.1089/zeb.2018.1594
    Ambient light and temperature affect reproductive function by regulating kisspeptin and gonadotrophin-releasing hormone (GnRH) in vertebrates. Melatonin and melatonin receptors, as well as the two-pore domain K+ channel-related K+ (TREK) channels, are affected by light and/or temperature; therefore, these molecules could modulate kisspeptin and GnRH against ambient light and temperature. In this study, we investigated the effect of light and temperature, which affect melatonin levels in gene expression levels of TREK channels, kisspeptin, and GnRH. We first investigated the effects of different light and temperature conditions on brain melatonin concentrations by ELISA. Fish were exposed to either constant darkness, constant light, high temperature (35°C), or low temperature (20°C) for 72 h. Brain melatonin levels were significantly high under constant darkness and high temperature. We further investigated the effects of high brain melatonin levels by constant darkness and high temperature on gene expression levels of melatonin receptors (mt1, mt2, and mel1c), TREK channels (trek1b, trek2a, and trek2b), gnrh3, and kiss2 in the adult zebrafish brain by real-time polymerase chain reaction. Fish were exposed to constant darkness or elevated temperatures (35°C) for 72 h. trek2a, kiss2, and gnrh3 levels were increased under constant darkness. High temperature decreased gene expression levels of mt1, mt2, mel1c, and gnrh3 in the preoptic area, whereas other genes remained unchanged. Melatonin receptors, TREK channels, gnrh3, and kiss2 responded differently under high melatonin conditions. The melatonin receptors and the TREK channels could play roles in the regulation of reproduction by environmental cues, especially ambient light and temperature.
    Matched MeSH terms: Brain/drug effects
  2. Caffeic acid protects tissue antioxidants and DNA content in methamphetamine induced tissue toxicity in Sprague Dawley rats
    Koriem KM, Abdelhamid AZ, Younes HF
    Toxicol. Mech. Methods, 2013 Feb;23(2):134-43.
    PMID: 22992185 DOI: 10.3109/15376516.2012.730561
    Caffeic acid (CA) (3,4-dihydroxycinnamic acid) is among the major hydroxycinnamic acids. Hydroxycinnamic acid is the major subgroup of phenolic compounds. Methamphetamine (METH) is a potent addictive psychostimulant. Chronic use and acute METH intoxication can cause substantial medical consequences, including spleen, kidney, liver and heart. The objective of the present study was to evaluate the antioxidant activity of CA to protect against oxidative stress and DNA damage to various organs in METH toxicity. Thirty-two male Sprague Dawley (SD) rats were divided into four equal groups: group 1 was injected (i.p) with saline (1 mL/kg) while groups 2,3 and 4 were injected (i.p) with METH (10 mg/kg) twice a day over five days period. Where 100 & 200 mg/kg of CA were injected (i.p) into groups 3 and 4, respectively one day before exposure to METH injections. Tissue antioxidants and DNA content were evaluated in different tissues. METH decreased glutathione (GSH) and glutathione peroxidase (GPx) levels while increased malondialdehyde (MDA), catalase (CAT) and protein carbonyl levels in brain (hypothalamus), liver, and kidney tissues of rats. METH increased hyperdiploidy in these tissues and DNA damage results. Prior treatment of CA to animals exposed to METH restores the above parameters to the normal levels and preserves the DNA content of these tissues. These results were supported by histopathological investigations. In conclusion, METH induced oxidative stress and DNA damage and pretreatment of CA before METH injections prevented tissue oxidative stress and DNA damage in METH-treated animals.
    Matched MeSH terms: Brain/drug effects
  3. Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats
    Hazim AI, Ramanathan S, Parthasarathy S, Muzaimi M, Mansor SM
    J Physiol Sci, 2014 May;64(3):161-9.
    PMID: 24464759 DOI: 10.1007/s12576-014-0304-0
    The effects of mitragynine on anxiety-related behaviours in the open-field and elevated plus-maze tests were evaluated. Male Sprague-Dawley rats were orally treated with mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) 60 min before behavioural testing. Mitragynine doses used in this study were selected on the basis of approximately human equivalent doses with reference to our previous literature reports. Acute administration of mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) increased central zone and open arms exploration in the open-field and elevated plus-maze tests respectively. These anxiolytic-like effects of mitragynine were effectively antagonized by intraperitoneal administration of naloxone (2 mg/kg), flumazenil (10 mg/kg), sulpiride (0.5 mg/kg) or SCH 23390 (0.02 mg/kg) 15 min before mitragynine treatments. These findings reveal that the acute administration of mitragynine produces anxiolytic-like effects and this could be possibly attributed to the interactions among opioidergic, GABAergic and dopaminergic systems in brain regions involved in anxiety.
    Matched MeSH terms: Brain/drug effects
  4. Protective antioxidant effect of Centella asiatica bioflavonoids on lead acetate induced neurotoxicity
    Ponnusamy K, Mohan M, Nagaraja HS
    Med J Malaysia, 2008 Jul;63 Suppl A:102.
    PMID: 19025005
    Lead (Pb) is a neurotoxic heavy metal and children in the developmental stage are particularly susceptible to toxic effects of lead exposure. The brain is the key organ involved in interpreting and responding to potential stressors. Epidemiological investigations have established the relationship between chronic lead exposure and cognitive impairments in young children. Excessive production of radical species plays an important role in neuronal pathology resulting from excitotoxic insults, therefore one plausible neuroprotective mechanism of bioflavonoids is partly relevant to their metal chelating and antioxidant properties. Centella asiatica (CA) is a tropical medicinal plant enriched with bioflavonoids and triterpenes and selenium, reported to rejuvenate the cells and promote physical and mental health. Bioflavonoids are claimed to be exert antimutagenic, neurotrophic and xenobiotics ameliorating and membrane molecular stabilizing effects. The objective of the present work is to study the protective antioxidant effect of pretreatment of CA extract (CAE) on lead acetate induced changes in oxidative biomarkers in the central nervous system (CNS) of mice.
    Matched MeSH terms: Brain/drug effects*
  5. Xanthone-enriched fraction of Garcinia mangostana and α-mangostin improve the spatial learning and memory of chronic cerebral hypoperfusion rats
    Tiang N, Ahad MA, Murugaiyah V, Hassan Z
    J Pharm Pharmacol, 2020 Nov;72(11):1629-1644.
    PMID: 32743849 DOI: 10.1111/jphp.13345
    OBJECTIVES: Xanthones isolated from the pericarp of Garcinia mangostana has been reported to exhibit neuroprotective effect.

    METHODS: In this study, the effect of xanthone-enriched fraction of Garcinia mangostana (XEFGM) and α-mangostin (α-MG) were investigated on cognitive functions of the chronic cerebral hypoperfusion (CCH) rats.

    KEY FINDINGS: HPLC analysis revealed that XEFGM contained 55.84% of α-MG. Acute oral administration of XEFGM (25, 50 and 100 mg/kg) and α-MG (25 and 50 mg/kg) before locomotor activity and Morris water maze (MWM) tests showed no significant difference between the groups for locomotor activity.

    CONCLUSIONS: However, α-MG (50 mg/kg) and XEFGM (100 mg/kg) reversed the cognitive impairment induced by CCH in MWM test. α-MG (50 mg/kg) was further tested upon sub-acute 14-day treatment in CCH rats. Cognitive improvement was shown in MWM test but not in long-term potentiation (LTP). BDNF but not CaMKII was found to be down-regulated in CCH rats; however, both parameters were not affected by α-MG. In conclusion, α-MG ameliorated learning and memory deficits in both acute and sub-acute treatments in CCH rats by improving the spatial learning but not hippocampal LTP. Hence, α-MG may be a promising lead compound for CCH-associated neurodegenerative diseases, including vascular dementia and Alzheimer's disease.

    Matched MeSH terms: Brain/drug effects*
  6. Chronic and acute ammonia toxicity in mudskippers, Periophthalmodon schlosseri and Boleophthalmus boddaerti: brain ammonia and glutamine contents, and effects of methionine sulfoximine and MK801
    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/drug effects
  7. Fulltext Habenula kisspeptin retrieves morphine impaired fear memory in zebrafish
    Sivalingam M, Ogawa S, Parhar IS
    Sci Rep, 2020 11 11;10(1):19569.
    PMID: 33177592 DOI: 10.1038/s41598-020-76287-9
    The habenula is an evolutionarily conserved brain structure, which has recently been implicated in fear memory. In the zebrafish, kisspeptin (Kiss1) is predominantly expressed in the habenula, which has been implicated as a modulator of fear response. Hence, in the present study, we questioned whether Kiss1 has a role in fear memory and morphine-induced fear memory impairment using an odorant cue (alarm substances, AS)-induced fear avoidance paradigm in adult zebrafish, whereby the fear-conditioned memory can be assessed by a change of basal place preference (= avoidance) of fish due to AS-induced fear experience. Subsequently, to examine the possible role of Kiss1 neurons-serotonergic pathway, kiss1 mRNA and serotonin levels were measured. AS exposure triggered fear episodes and fear-conditioned place avoidance. Morphine treatment followed by AS exposure, significantly impaired fear memory with increased time-spent in AS-paired compartment. However, fish administered with Kiss1 (10-21 mol/fish) after morphine treatment had significantly lower kiss1 mRNA levels but retained fear memory. In addition, the total brain serotonin levels were significantly increased in AS- and Kiss1-treated groups as compared to control and morphine treated group. These results suggest that habenular Kiss1 might be involved in consolidation or retrieval of fear memory through the serotonin system.
    Matched MeSH terms: Brain/drug effects
  8. Fulltext Effect of Berberis vulgaris L. root extract on ifosfamide-induced in vivo toxicity and in vitro cytotoxicity
    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/drug effects*
  9. Acute effects of methadone on EEG power spectrum and event-related potentials among heroin dependents
    Motlagh F, Ibrahim F, Rashid R, Shafiabady N, Seghatoleslam T, Habil H
    Psychopharmacology (Berl), 2018 Nov;235(11):3273-3288.
    PMID: 30310960 DOI: 10.1007/s00213-018-5035-0
    Methadone as the most prevalent opioid substitution medication has been shown to influence the neurophysiological functions among heroin addicts. However, there is no firm conclusion on acute neuroelectrophysiological changes among methadone-treated subjects as well as the effectiveness of methadone in restoring brain electrical abnormalities among heroin addicts. This study aims to investigate the acute and short-term effects of methadone administration on the brain's electrophysiological properties before and after daily methadone intake over 10 weeks of treatment among heroin addicts. EEG spectral analysis and single-trial event-related potential (ERP) measurements were used to investigate possible alterations in the brain's electrical activities, as well as the cognitive attributes associated with MMN and P3. The results confirmed abnormal brain activities predominantly in the beta band and diminished information processing ability including lower amplitude and prolonged latency of cognitive responses among heroin addicts compared to healthy controls. In addition, the alteration of EEG activities in the frontal and central regions was found to be associated with the withdrawal symptoms of drug users. Certain brain regions were found to be influenced significantly by methadone intake; acute effects of methadone induction appeared to be associative to its dosage. The findings suggest that methadone administration affects cognitive performance and activates the cortical neuronal networks, resulting in cognitive responses enhancement which may be influential in reorganizing cognitive dysfunctions among heroin addicts. This study also supports the notion that the brain's oscillation powers and ERPs can be utilized as neurophysiological indices for assessing the addiction treatment traits.
    Matched MeSH terms: Brain/drug effects
  10. Fulltext The anti-neuroinflammatory effects of Clinacanthus nutans leaf extract on metabolism elucidated through 1H NMR in correlation with cytokines microarray
    Ahmad Azam A, Ismail IS, Kumari Y, Shaikh MF, Abas F, Shaari K
    PLoS One, 2020;15(9):e0238503.
    PMID: 32925968 DOI: 10.1371/journal.pone.0238503
    Clinacanthus nutans (CN) (Acanthaceae) is well-known for its anti-inflammatory properties among Asian communities; however, there are currently no data specifically focused on the anti-inflammatory effects of CN on the brain tissue. Neuroinflammation is a common consequence of toxin intrusion to any part of the central nervous system (CNS). As an innate immune response, the CNS may react through both protective and/or toxic actions due to the activation of neuron cells producing pro- and/or anti-inflammatory cytokines in the brain. The unresolved activation of the inflammatory cytokines' response is associated with the pathogenesis of neurological disorders. The present study aimed to decipher the metabolic mechanism on the effects of 14 days oral treatment with CN aqueous extract in induced-lipopolysaccharides (LPS) rats through 1H NMR spectroscopic biomarker profiling of the brain tissue and the related cytokines. Based on the principal component analysis (PCA) of the nuclear magnetic resonance (NMR) spectral data, twenty-one metabolites in the brain tissue were profiled as biomarkers for the LPS (10 μL)-induced neuroinflammation following intracerebroventricular injection. Among the twenty-one biomarkers in the neuroinflammed rats, CN treatment of 1000 and 500 mg/kg BW successfully altered lactate, pyruvate, phosphorylcholine, glutamine, and α-ketoglutarate when compared to the negative control. Likewise, statistical isolinear multiple component analysis (SIMCA) showed that treatments by CN and the positive control drug, dextromethorphan (DXM, 5 mg/kg BW), have anti-neuroinflammatory potential. A moderate correlation, in the orthogonal partial least squares (OPLS) regression model, was found between the spectral metabolite profile and the cytokine levels. The current study revealed the existence of high levels of pro-inflammatory cytokines, namely IL-1α, IL-1β, and TNF-α in LPS-induced rats. Both CN dose treatments lowered IL-1β significantly better than DXM Interestingly, DXM and CN treatments both exhibited the upregulation of the anti-inflammatory cytokines IL-2 and 4. However, DXM has an advantage over CN in that the former also increased the expression of IL-10 of anti-inflammatory cytokines. In this study, a metabolomics approach was successfully applied to discover the mechanistic role of CN in controlling the neuroinflammatory conditions through the modulation of complex metabolite interactions in the rat brain.
    Matched MeSH terms: Brain/drug effects*
  11. Fulltext A systems biology approach towards the identification of candidate therapeutic genes and potential biomarkers for Parkinson's disease
    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/drug effects
  12. Modulation of LOX and COX pathways via inhibition of amyloidogenesis contributes to mitoprotection against β-amyloid oligomer-induced toxicity in an animal model of Alzheimer's disease in rats
    Kalra J, Kumar P, Majeed AB, Prakash A
    Pharmacol. Biochem. Behav., 2016 Jul-Aug;146-147:1-12.
    PMID: 27106205 DOI: 10.1016/j.pbb.2016.04.002
    Several lines of evidence indicate that beta amyloid (β-A) production, neurofibrillary tangles and neuroinflammation are interrelated in the pathogenesis of Alzheimer's disease (AD). AD is associated with enhanced β-A production and accumulation resulting in neuroinflammation probably via activation of lipoxygenase (LOX) and cyclooxygenase (COX) pathways. Therefore, the present study was designed to investigate the role of LOX and COX inhibitors (zafirlukast and valdecoxib) in amyloidogenesis in β-A1-42 oligomer induced experimental AD in rats. The behavioral activities were assessed using actophotometer, novel object recognition test (ORT), Morris water maze (MWM) followed by biochemical assessments, determination of proinflammatory cytokines and mediators (TNF-α, IL-1β and PGE2), β-A1-42 levels and histopathological analysis. ICV administration of β-A1-42 oligomer produced significant impairment in memory consolidation. In addition to this significant increase in mito-oxidative stress, neuroinflammatory markers, acetylcholinesterase (AChE) toxicity, β-A1-42 level, neuronal cell death and neuroinflammation are more profound in β-A1-42 oligomer treated AD rats. Administration of zafirlukast (15 and 30mg/kg), and valdecoxib (5 and 10mg/kg) significantly improved the behavioral performances and showed significant reversal of mito-oxidative damage declining the neuroinflammation in β-A1-42 oligomer treated rats. Furthermore, more profound effects were observed at the sub-therapeutic dose combination of zafirlukast (15mg/kg) and valdecoxib (5mg/kg). The results of the present study indicate that protective effects of zafirlukast and valdecoxib are achieved through the blockade of release of LOX and COX metabolites therefore, representing a new therapeutic target for treating AD and other neurodegenerative disorders.
    Matched MeSH terms: Brain/drug effects
  13. Chronotherapeutic effect of fisetin on expression of urea cycle enzymes and inflammatory markers in hyperammonaemic rats
    Subramanian P, Jayakumar M, Jayapalan JJ, Hashim OH
    Pharmacol Rep, 2014 Dec;66(6):1037-42.
    PMID: 25443732 DOI: 10.1016/j.pharep.2014.06.018
    BACKGROUND: Elevated blood ammonia leads to hyperammonaemia that affects vital central nervous system (CNS) functions. Fisetin, a naturally occurring flavonoid, exhibits therapeutic benefits, such as anti-cancer, anti-diabetic, anti-oxidant, anti-angiogenic, neuroprotective and neurotrophic effects.

    METHODS: In this study, the chronotherapeutic effect of fisetin on ammonium chloride (AC)-induced hyperammonaemic rats was investigated, to ascertain the time point at which the maximum drug effect is achieved. The anti-hyperammonaemic potential of fisetin (50mg/kg b.w. oral) was analysed when administered to AC treated (100mg/kg b.w. i.p.) rats at 06:00, 12:00, 18:00 and 00:00h. Amelioration of pathophysiological conditions by fisetin at different time points was measured by analysing the levels of expression of liver urea cycle enzymes (carbamoyl phosphate synthetase-I (CPS-I), ornithine transcarbamoylase (OTC) and argininosuccinate synthetase (ASS)), nuclear transcription factor kappaB (NF-κB p65), brain glutamine synthetase (GS) and inducible nitric oxide synthase (iNOS) by Western blot analysis.

    RESULTS: Fisetin increased the expression of CPS-I, OTC, ASS and GS and decreased iNOS and NF-κB p65 in hyperammonaemic rats. Fisetin administration at 00:00h showed more significant effects on the expression of liver and brain markers, compared with other time points.

    CONCLUSIONS: Fisetin could exhibit anti-hyperammonaemic effect owing to its anti-oxidant and cytoprotective influences. The temporal variation in the effect of fisetin could be due to the (i) chronopharmacological, chronopharmacokinetic properties of fisetin and (ii) modulations in the endogenous circadian rhythms of urea cycle enzymes, brain markers, redox enzymes and renal clearance during hyperammonaemia by fisetin. However, future studies in these lines are necessitated.

    Matched MeSH terms: Brain/drug effects
  14. Type 3 diabetes (Alzheimer's disease): new insight for promising therapeutic avenues
    Candasamy M, Mohamed Elhassan SA, Kumar Bhattamisra S, Hua WY, Sern LM, Binti Busthamin NA, et al.
    Panminerva Med, 2020 Sep;62(3):155-163.
    PMID: 32208408 DOI: 10.23736/S0031-0808.20.03879-3
    Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D) are two of the most commonly occurring diseases worldwide, especially among the elderly population. In particular, the increased prevalence of AD has imposed tremendous psychological and financial burdens on society. Growing evidence suggests both AD and T2D share many similar pathological traits. AD is characterized as a metabolic disorder whereby the glucose metabolism in the brain is impaired. This closely resembles the state of insulin resistance in T2D. Insulin resistance of the brain has been heavily implicated two prominent pathological features of AD, Aβ plaques and neurofibrillary tangles. Brain insulin resistance is known to elicit a positive feed-forward loop towards the formation of AD pathology in which they affect each other in a synergistic manner. Other physiological traits shared between the two diseases include inflammation, oxidative stress and autophagic dysfunction, which are also closely associated with brain insulin resistance. In this review and depending on these underlying pathways that link these two diseases, we have discussed the potential therapeutic implications of AD. By expanding our knowledge of the overlapping pathophysiology involved, we hope to provide scientific basis to the discovery of novel therapeutic strategies to improve the clinical outcomes of AD in terms of diagnosis and treatment.
    Matched MeSH terms: Brain/drug effects
  15. Fulltext Effects of Aging and Tocotrienol-Rich Fraction Supplementation on Brain Arginine Metabolism in Rats
    Mazlan M, Hamezah HS, Taridi NM, Jing Y, Liu P, Zhang H, et al.
    Oxid Med Cell Longev, 2017;2017:6019796.
    PMID: 29348790 DOI: 10.1155/2017/6019796
    Accumulating evidence suggests that altered arginine metabolism is involved in the aging and neurodegenerative processes. This study sought to determine the effects of age and vitamin E supplementation in the form of tocotrienol-rich fraction (TRF) on brain arginine metabolism. Male Wistar rats at ages of 3 and 21 months were supplemented with TRF orally for 3 months prior to the dissection of tissue from five brain regions. The tissue concentrations of L-arginine and its nine downstream metabolites were quantified using high-performance liquid chromatography and liquid chromatography tandem mass spectrometry. We found age-related alterations in L-arginine metabolites in the chemical- and region-specific manners. Moreover, TRF supplementation reversed age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum. Multiple regression analysis revealed a number of significant neurochemical-behavioral correlations, indicating the beneficial effects of TRF supplementation on memory and motor function.
    Matched MeSH terms: Brain/drug effects
  16. Neurophysiological symptoms and aspartame: What is the connection?
    Choudhary AK, Lee YY
    Nutr Neurosci, 2018 Jun;21(5):306-316.
    PMID: 28198207 DOI: 10.1080/1028415X.2017.1288340
    Aspartame (α-aspartyl-l-phenylalanine-o-methyl ester), an artificial sweetener, has been linked to behavioral and cognitive problems. Possible neurophysiological symptoms include learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia. The consumption of aspartame, unlike dietary protein, can elevate the levels of phenylalanine and aspartic acid in the brain. These compounds can inhibit the synthesis and release of neurotransmitters, dopamine, norepinephrine, and serotonin, which are known regulators of neurophysiological activity. Aspartame acts as a chemical stressor by elevating plasma cortisol levels and causing the production of excess free radicals. High cortisol levels and excess free radicals may increase the brains vulnerability to oxidative stress which may have adverse effects on neurobehavioral health. We reviewed studies linking neurophysiological symptoms to aspartame usage and conclude that aspartame may be responsible for adverse neurobehavioral health outcomes. Aspartame consumption needs to be approached with caution due to the possible effects on neurobehavioral health. Whether aspartame and its metabolites are safe for general consumption is still debatable due to a lack of consistent data. More research evaluating the neurobehavioral effects of aspartame are required.
    Matched MeSH terms: Brain/drug effects
  17. 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: Brain/drug effects*
  18. Fulltext Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats
    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/drug effects
  19. Effects of acute ammonia toxicity on nitric oxide (NO), citrulline-NO cycle enzymes, arginase and related metabolites in different regions of rat brain
    Swamy M, Zakaria AZ, Govindasamy C, Sirajudeen KN, Nadiger HA
    Neurosci Res, 2005 Oct;53(2):116-22.
    PMID: 16009439
    Nitric oxide (NO) is involved in many pathophysiological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS) enzymes. Citrulline formed as a by-product of the NOS reaction, can be recycled to arginine by successive actions of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) via the citrulline-NO cycle. Hyperammonemia is known to cause poorly understood perturbations of the citrulline-NO cycle. To understand the role of citrulline-NO cycle in hyperammonemia, NOS, ASS, ASL and arginase activities, as well as nitrate/nitrite (NOx), arginine, ornithine, citrulline, glutamine, glutamate and GABA were estimated in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats subjected to acute ammonia toxicity. NOx concentration and NOS activity were found to increase in all the regions of brain in acute ammonia toxicity. The activities of ASS and ASL showed an increasing trend whereas the arginase was not changed. The results of this study clearly demonstrated the increased formation of NO, suggesting the involvement of NO in the pathophysiology of acute ammonia toxicity. The increased activities of ASS and ASL suggest the increased and effective recycling of citrulline to arginine in acute ammonia toxicity, making NO production more effective and contributing to its toxic effects.
    Matched MeSH terms: Brain/drug effects*
  20. Citalopram (antidepressant) administration causes sexual dysfunction in male mice through RF-amide related peptide in the dorsomedial hypothalamus
    Soga T, Wong DW, Clarke IJ, Parhar IS
    Neuropharmacology, 2010 Jul-Aug;59(1-2):77-85.
    PMID: 20381503 DOI: 10.1016/j.neuropharm.2010.03.018
    Citalopram is the most potent selective serotonin reuptake inhibitor (SSRI) which is used as an antidepressant but causes sexual dysfunction. Whether citalopram induced sexual dysfunction is a result of gonadotropin-releasing hormone (GnRH), kisspeptin or RF-amide related peptide (RFRP) alteration is unknown. In this study, we tested mice for sexual behavior after vehicle (0.9% NaCl) and citalopram treatment (5 mg/kg) daily for 1 day (acute) and 21 or 28 days (chronic). Effects of acute and chronic treatments on neuronal numbers and mRNA expression of GnRH, kisspeptin and RFRP were measured. In addition, RFRP fiber projections to preoptic (POA)-GnRH neurons were analyzed using double-label immunohistochemistry. The expression of 14 different serotonin receptor types mRNA was examined in immunostained laser dissected single RFRP neurons in the dorsomedial hypothalamus (DMH), however only 11 receptors types were identified. Acute citalopram treatment did not affect sexual behavior, whereas, the total duration of intromission was reduced with chronic treatment. There was no effect in the expression of kisspeptin (neuronal numbers and mRNA) in the anteroventral periventricular nucleus and the arcuate nucleus and expression of GnRH (neuronal numbers and mRNA) in the POA after citalopram treatment. However, RFRP neuronal numbers in the DMH and fiber projections to the POA were significantly increased after chronic citalopram treatment, which suggests citalopram induced inhibition of sexual behavior involves the modulation of RFRP through serotonin receptors in the DMH.
    Matched MeSH terms: Brain/drug effects
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