DOCSLIB.ORG

Tetrahydroisoquinoline Neurotoxins in Parkinson Disease Michael G

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 5-2010 Tetrahydroisoquinoline Neurotoxins in Parkinson Disease Michael G. DeCuypere University of Tennessee Health Science Center Follow this and additional works at: https://dc.uthsc.edu/dissertations Part of the Nervous System Diseases Commons, and the Neurosciences Commons Recommended Citation DeCuypere, Michael G. , "Tetrahydroisoquinoline Neurotoxins in Parkinson Disease" (2010). Theses and Dissertations (ETD). Paper 55. http://dx.doi.org/10.21007/etd.cghs.2010.0067. This Dissertation is brought to you for free and open access by the College of Graduate Health Sciences at UTHSC Digital Commons. It has been accepted for inclusion in Theses and Dissertations (ETD) by an authorized administrator of UTHSC Digital Commons. For more information, please contact [email protected]. Tetrahydroisoquinoline Neurotoxins in Parkinson Disease Document Type Dissertation Degree Name Doctor of Philosophy (PhD) Program Biomedical Sciences Track Neuroscience Research Advisor Mark S. LeDoux, M.D., Ph.D. Committee Joseph C. Callaway, Ph.D. Angela R. Cantrell, Ph.D. Duane D. Miller, Ph.D. Lawrence T. Reiter, Ph.D. DOI 10.21007/etd.cghs.2010.0067 This dissertation is available at UTHSC Digital Commons: https://dc.uthsc.edu/dissertations/55 TETRAHYDROISOQUINOLINE NEUROTOXINS AND PARKINSON DISEASE A Dissertation Presented for The Graduate Studies Council The University of Tennessee Health Science Center In Partial Fulfillment Of the Requirements for the Degree Doctor of Philosophy From The University of Tennessee By Michael G. DeCuypere May 2010 Chapter 2 © 2008 by Wiley-Liss, Inc. Chapter 3 © 2008 by International Society for Neurochemistry. All other material © 2010 by Michael G. DeCuypere. All rights reserved. ii DEDICATION To my loving wife, best friend and eternal companion Norma. With love and thanks for supporting me in all my endeavors into neuroscience and neurosurgery. You make my journey worthwhile. iii ACKNOWLEDGEMENTS First and foremost, I would like to thank my research advisor and mentor, Dr. Mark LeDoux, for the training I received in his laboratory. His encouragement, advice and supervision in my research and medical endeavors are much appreciated. Of utmost importance to my career, I appreciate his time, effort and motivation in my education on scientific writing. I would like to thank the members of my graduate committee, Drs. Angela Cantrell, Lawrence Reiter, Joseph Callaway and Duane Miller, for their valuable comments and advice on my qualifying exam, research proposal and dissertation formulation. I would also like to sincerely thank all the current and former members in Dr. LeDoux’s laboratory: Dr. Jianfeng Xiao, Dr. Suzhen Gong and Dr. Yu Zhao, for their technical assistance, suggestions and camaraderie. In particular, I would like to thank Dr. Yu Zhao for her extensive training and assistance in cell culture techniques and valuable input regarding my experiments. Her scientific knowledge and friendship were welcoming and valued in the often-times rough seas of graduate school. During my graduate school training I have had the privilege to learn from several faculty members in the Department of Anatomy and Neurobiology. My sincere thanks to: Drs. Robert Foehring, William Armstrong and Robert Waters for their instruction in neuronal physiology; to Dr. Matt Ennis for instruction in neuroanatomy; to Drs. Melburn Park and Lawrence Reiter for instruction on techniques in microscopy; to Drs. Angela Cantrell and Thomas Schikorski for their instruction on critical review of literature. I am especially grateful to Dr. Pat Ryan, IPBS program director, and Dr. Joseph Callaway, neuroscience graduate program director, who provided me with direction and support from the very beginning of my foray in neuroscience. Many thanks to the staff in the Departments of Neurology and Anatomy and Neurobiology, including Brenda Smith for her administrative help in graduate school and Mary Reed, Bobbie Scott, and Frances Grigsby for their help in reagent purchasing and administrative work. I would especially thank my wife and my extended family for their incredible love and support throughout my graduate training. Finally, I would like to thank the National Institute of Neurological Disorders and Stroke for financial support (R03-NS049123 to MSL). iv ABSTRACT The goal of this dissertation work was to (1) determine the distribution of several tetrahydroisoquinoline (TIQ) derivatives in rodent, normal human and Parkinson disease (PD) brain, (2) quantify the levels of these TIQ derivatives in common food sources in an effort to link specific food intake patterns with the development of PD and (3) examine the neurotoxicity of select TIQ derivatives in human dopaminergic cell culture. The TIQs are a family of monoamine alkaloids that share structural homology with 1-methyl-4- phenyl-1,2,3,6-tetrahyrdropyridine (MPTP), can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell death. In our studies, we utilize enantiomeric-selective high-performance liquid chromatography with electrochemical detection (HPLC-EC) and liquid chromatography with tandem mass spectroscopy (LC-MS/MS) to determine the concentrations of TIQ derivatives in brain, as well as in common dietary plants in the United States. The dopaminergic SH-SY5Y human neuroblastoma cell line was utilized to document the neurotoxicity of N-methylated salsolinol derivatives. Several TIQ derivatives were detected in all regions subjected to analysis. In general, salsolinols were present at higher concentrations than TIQ and its benzyl and methyl derivatives, especially in human brain. Moreover, salsolinols were concentrated in areas with increased dopamine synthesis and turnover such as the ventral midbrain and striatum, respectively. Significantly lower levels of (R)salsolinol, (S)salsolinol, N- methyl-(R)salsolinol and N-methyl-(S)salsolinol were found in the caudate nuclei of PD in comparison with normal human brain. N-methyl-norsalsolinol was detected in all regions of rodent and human brain subjected to analysis. In comparison to normal human controls, N-methyl-norsalsolinol levels were significantly lower in the substantia nigra and caudate nuclei from PD patients. N-methyl-norsalsolinol-immunoreactivity co- localized with a general neuronal marker and a monoaminergic cell marker. N-methyl- norsalsolinol-immunoreactivity was not observed in glia. Our analysis of common foods revealed high concentrations of TIQ derivatives in banana, cherry, peach, grapefruit, avocado, button mushroom, leaf lettuce and celery. Enantiomeric salsolinol derivatives were detected as racemic mixtures, without evidence of stereoselective synthesis. Utilizing a lifetime food-item intake questionnaire, we identified trends for increased intake of several plants products in PD patients. Members of the rue (Rutaceae), banana (Musaceae), gourd (Cucurbitaceae), carrot (Apiaceae) and nightshade (Solanaceae) families were found to be highly consumed in both normal human and PD groups, and to concentrate several potentially neurotoxic TIQ derivatives. We correlated indices of cellular energy production and cell viability in dopaminergic SH-SY5Y cells after exposure to N-methyl-norsalsolinol and N-methyl- (R/S)salsolinol. Both toxins induce dose-dependent decreases in cell survival with LC50 values of 0.305 mM and 0.377 mM after 24 hrs, respectively. These results suggest that cell death induced by these N-methylated salsolinols is due to impairment of cellular energy supply, caused in particular by inhibition of mitochondrial complex I. Their concentration in dopaminergic regions of human brain and relatively potent cytotoxicity among TIQs makes these compounds strong candidates for both an endogenous and exogenous link to cell death in PD. v TABLE OF CONTENTS CHAPTER 1. INTRODUCTION ........................................................................................ 1 1.1 PARKINSON DISEASE ................................................................................... 1 1.1.1 Clinical Features .................................................................................. 1 1.1.1.1 Tremor .................................................................................... 1 1.1.1.2 Rigidity .................................................................................... 2 1.1.1.3 Bradykinesia ........................................................................... 2 1.1.1.4 Parkinsonian Gait ................................................................... 3 1.1.1.5 Secondary Manifestations ...................................................... 3 1.1.2 Natural History ..................................................................................... 5 1.1.3 Epidemiology ....................................................................................... 7 1.1.3.1 Incidence ................................................................................ 7 1.1.3.2 Prevalence .............................................................................. 8 1.1.3.3 Geographic Environments ...................................................... 9 1.1.3.4 Genetic Risk Factors .............................................................. 9 1.1.4 Cellular and Molecular Pathology ...................................................... 10 1.2 THE TETRAHYDROISOQUINOLINES ........................................................
Recommended publications
  • Chiral CE Separation of Dopamine-Derived Neurotoxins

    Chiral CE Separation of Dopamine-Derived Neurotoxins

    ANALYTICAL SCIENCES FEBRUARY 2005, VOL. 21 115 2005 © The Japan Society for Analytical Chemistry Chiral CE Separation of Dopamine-Derived Neurotoxins Zhe QUAN,* Yaru SONG,* Gladys PETERS,* Ming SHENWU,* Yinghong SHENG,* Huey-Min HWANG,** and Yi-Ming LIU*† *Department of Chemistry, Jackson State University, 1400 Lynch St., Jackson, MS 39217, USA **Department of Biology, Jackson State University, 1400 Lynch St., Jackson, MS 39217, USA An enantiomeric separation of dopamine-derived neurotoxins by capillary electrophoresis has been developed. Tetrahydroisoquinoline (TIQ), dopamine (DA), (R/S)-1-benzyl-TIQ (BTIQ), (R/S)-6,7-dihydroxy-1-methyl-TIQ (salsolinol, Sal), and (R/S)-6,7-dihydroxy-1, 2-dimethyl-TIQ (N-methyl-salsolinol, NMSal) were studied as model compounds. The CE running buffer (50 mM phosphate buffer at pH 3.0) contained 1.5 M urea and 12 mM β-CD as a chiral selector. During separation, the (R)-enantiomers formed more stable inclusion complexes with β-CD, and thus had a longer migration time than their optical antipodes. It was noticed that the recovery rates of these TIQ derivatives were very poor (< 15%) during protein precipitation, a procedure widely used for cleaning up biological samples. The recovery was significantly improved by pre-mixing the sample with a surfactant (e.g., sodium hexanesulfonate or Triton X-100) to reduce the co-precipitation. The present method in combination with electrospray ionization tandem mass spectrometry (ESI-MS/MS) was applied to study samples obtained from in vitro incubation of two catecholamines, dopamine and epinine, with aldehydes forming neurotoxins including (S)- and (R)-NMSal enantiomers. The later is known to induce Parkinsonism in rats.
  • The Neurochemical Effects of Several Carboxylated Tetrahydroisoquinolines

    The Neurochemical Effects of Several Carboxylated Tetrahydroisoquinolines

    Loyola University Chicago Loyola eCommons Dissertations Theses and Dissertations 1983 The Neurochemical Effects of Several Carboxylated Tetrahydroisoquinolines Jerome James Hannigan Loyola University Chicago Follow this and additional works at: https://ecommons.luc.edu/luc_diss Part of the Medicine and Health Sciences Commons Recommended Citation Hannigan, Jerome James, "The Neurochemical Effects of Several Carboxylated Tetrahydroisoquinolines" (1983). Dissertations. 2225. https://ecommons.luc.edu/luc_diss/2225 This Dissertation is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Dissertations by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 1983 Jerome James Hannigan The Neurochemical Effects of Several Carboxylated Tetrahydroisoquinolines by Jerome James Hannigan A Dissertation Submitted to the Faculty of the Graduate School of Loyola University of Chicago. in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY June 1983 .,.. ·-. ~ 1983, Jerome James Hannigan ACKNOWLEDGEMENTS I would like to acknowledge Dr. Michael Collins for his role in training me to be a research scientist. His supervision has been helpful in pursuing the answers to the questions addressed by this dissertation. I wish to thank Dr. Byron Anderson for encouraging me to pursue a career in Biochemistry. I have come to share his love for science. I could not have survived graduate school without the help and guidance of the faculty of the Department of Biochemistry. To my fellow students I owe a debt of gratitude.
  • THE CLINICAL ASSESSMENT of the PATIENT with EARLY DEMENTIA S Cooper, J D W Greene V15

    THE CLINICAL ASSESSMENT of the PATIENT with EARLY DEMENTIA S Cooper, J D W Greene V15

    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2005.081133 on 16 November 2005. Downloaded from THE CLINICAL ASSESSMENT OF THE PATIENT WITH EARLY DEMENTIA S Cooper, J D W Greene v15 J Neurol Neurosurg Psychiatry 2005;76(Suppl V):v15–v24. doi: 10.1136/jnnp.2005.081133 ementia is a clinical state characterised by a loss of function in at least two cognitive domains. When making a diagnosis of dementia, features to look for include memory Dimpairment and at least one of the following: aphasia, apraxia, agnosia and/or disturbances in executive functioning. To be significant the impairments should be severe enough to cause problems with social and occupational functioning and the decline must have occurred from a previously higher level. It is important to exclude delirium when considering such a diagnosis. When approaching the patient with a possible dementia, taking a careful history is paramount. Clues to the nature and aetiology of the disorder are often found following careful consultation with the patient and carer. A focused cognitive and physical examination is useful and the presence of specific features may aid in diagnosis. Certain investigations are mandatory and additional tests are recommended if the history and examination indicate particular aetiologies. It is useful when assessing a patient with cognitive impairment in the clinic to consider the following straightforward questions: c Is the patient demented? c If so, does the loss of function conform to a characteristic pattern? c Does the pattern of dementia conform to a particular pattern? c What is the likely disease process responsible for the dementia? An understanding of cognitive function and its anatomical correlates is necessary in order to ascertain which brain areas are affected.
  • Relevance of the Anti-Inflammatory Properties of Curcumin in Neurodegenerative Diseases and Depression

    Relevance of the Anti-Inflammatory Properties of Curcumin in Neurodegenerative Diseases and Depression

    Molecules 2014, 19, 20864-20879; doi:10.3390/molecules191220864 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Relevance of the Anti-Inflammatory Properties of Curcumin in Neurodegenerative Diseases and Depression Yousef Tizabi *, Laura L. Hurley, Zakiya Qualls and Luli Akinfiresoye Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, USA; E-Mails: [email protected] (L.L.H.); [email protected] (Z.Q.); [email protected] (L.A.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-202-806-9719, Fax: +1-202-806-4453. External Editors: Sahdeo Prasad and Bharat B. Aggarwal Received: 21 October 2014; in revised form: 5 December 2014 / Accepted: 8 December 2014 / Published: 12 December 2014 Abstract: This review is an attempt to summarize our current understanding of curcumin’s potential as a neuroprotectant and an antidepressant. This dual property confers a unique advantage to this herbal medication, believed to be devoid of any major side effects, to combat commonly observed co-morbid conditions of a neurodegenerative and a neuropsychiatric disorder. Moreover, in line with the theme of this series, the role of inflammation and stress in these diseases and possible anti-inflammatory effects of curcumin, as well as its interaction with signal transduction proteins as a common denominator in its varied mechanisms of action, are also discussed. Thus, following a brief introduction of curcumin’s pharmacology, we present research suggesting how its anti-inflammatory properties have therapeutic potential in treating a devastating neurological disorder (Parkinson’s disease = PD) and a debilitating neuropsychiatric disorder (major depressive disorder = MDD).
  • Effects of Smoking and Gender on Tetrahydroisoquinolines and Beta-Carbolines in a Healthy Population and During Alcohol Detoxification

    Effects of Smoking and Gender on Tetrahydroisoquinolines and Beta-Carbolines in a Healthy Population and During Alcohol Detoxification

    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2008 Effects of Smoking and Gender on Tetrahydroisoquinolines and Beta-Carbolines in a Healthy Population and During Alcohol Detoxification Satjit Singh Brar Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/902 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. © Satjit Singh Brar 2008 All Rights Reserved EFFECTS OF SMOKING AND GENDER ON TETRAHYDROISOQUINOLINES AND β–CARBOLINES IN A HEALTHY POPULATION AND DURING ALCOHOL DETOXIFICATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by SATJIT SINGH BRAR B.S., University of California at Santa Barbara, 1998 Director: Jürgen Venitz, MD, Ph.D. Associate Professor, Department of Pharmaceutics Virginia Commonwealth University Richmond, Virginia May 2008 ii Acknowledgements Jürgen Venitz, first and foremost, for giving me the opportunity to pursue graduate studies under his guidance. His mentoring in academics and research has been truly motivating and inspirational. Members of my graduate committee, Drs. Jürgen Venitz, John Rosecrans, Patricia Slattum, Vijay Ramchandani, H. Thomas Karnes, and Hee-Yong Kim for their efforts, patience and time for serving on my committee. Patricia Slattum for her advice and encouragement. She has provided valuable aid over the years by giving guidance throughout my tenure in the Pharm.D./Ph.D.
  • On Dopamine Secretion and Its Intracellular Dynamics in Rat Pheochromocytoma PC 12 Cells

    On Dopamine Secretion and Its Intracellular Dynamics in Rat Pheochromocytoma PC 12 Cells

    Effects of an endogenous dopaminergic neurotoxin, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (norsalsolinol), on Title dopamine secretion and its intracellular dynamics in rat pheochromocytoma PC 12 cells Author(s) MARUYAMA, Yutaka Citation Japanese Journal of Veterinary Research, 49(1), 47-48 Issue Date 2001-05-31 Doc URL http://hdl.handle.net/2115/2878 Type bulletin (article) File Information KJ00002400340.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Jpn. J. Vet. Res. 49 ( 1 ), (2001) Information 47 Effects of an endogenous dopaminergic neurotoxin, 6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline (norsalsolinoO, on dopamine secretion and its intracellular dynamics in rat pheochromocytoma PC 12 cells Yutaka Maruyama Laboratory of Toxicology Department of Environmental Veterinary Sciences Graduate School of Veterinary Medicine Hokkaido University, Sapporo 060-0818, Japan Naturally occurring neurotoxins, 6, 7- (vmax) of 55. 6 ± 3. 5 pmollminJrng protein (n dihydroxy-1, 2, 3, 4 -tetrahydroisoquinolines = 4 ). The uptake of norsalsolinol was sensi­ (DHTIQs), have been thought to be the tive to two dopamine transporter (DAT) in­ causative agents of parkinsonism. DHTIQs, hibitors, GBR-12909 and reserpine, but was including norsalsolinol, have been found in less sensitive to desipramine, a noradrenaline the mammalian central nervous system. Nor­ transporter inhibitor. Dopamine, an endoge­ salsolinol can be formed in parkinsonian pa­ nous DAT substrate, inhibited norsalsolinol tients. However, the effects of DHTIQs on the uptake into PC 12 cells. The Km and Vmax secretion of dopamine, as well as other neuro­ values of the uptake of norsalsolinol in the transmitters, have not been elucidated. In presence of 100 11M dopamine were 241.
  • Inhibition of Rodent Brain Monoamine Oxidase and Tyrosine Hydroxylase by Endogenous Compounds – 1,2,3,4-Tetrahydroisoquinoline Alkaloids

    Inhibition of Rodent Brain Monoamine Oxidase and Tyrosine Hydroxylase by Endogenous Compounds – 1,2,3,4-Tetrahydroisoquinoline Alkaloids

    Copyright © 2004 by Institute of Pharmacology Polish Journal of Pharmacology Polish Academy of Sciences Pol. J. Pharmacol., 2004, 56, 727734 ISSN 1230-6002 INHIBITION OF RODENT BRAIN MONOAMINE OXIDASE AND TYROSINE HYDROXYLASE BY ENDOGENOUS COMPOUNDS – 1,2,3,4-TETRAHYDROISOQUINOLINE ALKALOIDS Antoni Patsenka, Lucyna Antkiewicz-Michaluk Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smêtna 12, PL 31-343 Kraków, Poland Inhibition of rodent brain monoamine oxidase and tyrosine hydroxylase by endogenous compounds – 1,2,3,4-tetrahydroisoquinoline alkaloids. A. PATSENKA, L. ANTKIEWICZ-MICHALUK. Pol. J. Pharmacol., 2004, 56, 727–734. Four different noncatecholic and one catecholic tetrahydroisoquinolines (TIQs), cyclic condensation derivatives of b-phenylethylamine and dopa- mine with aldehydes or keto acids, were examined for the inhibition of rat and mouse brain monoamine oxidase (MAO) and rat striatum tyrosine hy- droxylase (TH) activity. Simple noncatecholic TIQs were found to act as moderate (TIQ, N-methyl-TIQ, 1-methyl-TIQ) or weak (1-benzyl-TIQ), MAO B and MAO A inhibitors. 1-Methyl-TIQ inhibited more potently MAO-A than MAO-B; the similar but more modest effect was exerted by salsolinol. Only salsolinol markedly inhibited TH activity, being competitive with the enzyme biopterin cofactor. The inhibition of MAO and TH by TIQs is discussed in relation to their ability to regulate monoamine metabolism. Key words: monoamine oxidase, tyrosine hydroxylase, inhibition of en- zyme activity, tetrahydroisoquinoline derivatives correspondence; e-mail: [email protected] A. Patsenka, L. Antkiewicz-Michaluk Abbreviations: BBB – blood-brain barrier,BH" been found to be toxic to dopaminergic neurons – 5,6,7,8-tetrahydrobiopterin, CSF – cerebrospinal and their concentration has been shown to increase fluid, 5-HT – 5-hydroxytryptamine, MAO – mono- in parkinsonian brains or cerebrospinal fluid (CSF) amine oxidase, MPTP – 1-methyl-4-phenyl-1,2,3,6- [12].
  • HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits

    HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits

    cells Review HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits Kristen A. McLaurin †, Michael Harris †, Victor Madormo †, Steven B. Harrod, Charles F. Mactutus and Rosemarie M. Booze * Department of Psychology, University of South Carolina, Columbia, SC 29208, USA; [email protected] (K.A.M.); [email protected] (M.H.); [email protected] (V.M.); [email protected] (S.B.H.); [email protected] (C.F.M.) * Correspondence: [email protected] † These authors contributed equally. Abstract: Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 Citation: McLaurin, K.A.; Harris, M.; seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, Madormo, V.; Harrod, S.B.; Mactutus, C.F.; Booze, R.M. HIV-Associated the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit Apathy/Depression and observed following chronic HIV-1 viral protein exposure.
  • Glial Changes in Atypical Parkinsonian Syndromes

    Glial Changes in Atypical Parkinsonian Syndromes

    Glial changes in atypical parkinsonian syndromes Yun Ju Christine Song A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy August 2008 University of New South Wales Department of Anatomy Supervisors: Professor Glenda M Halliday Dr Yue Huang 1 Acknowledgements It feels surreal realising that I have come to the end of this unbelievably challenging but rewarding journey. I could not have come this far without the amazing help and guidance from so many important people and I am deeply grateful to everybody who has contributed to the steps I have taken in completing this journey. To my supervisor Glenda Halliday, thank you so much for all your encouragement and guidance. I have continuously learnt so much from you and there have been countless times where I have been in constant awe of your drive, passion and knowledge about these movement disorders. Thank you for all your teachings and enthusiasm for my work, and believing that I could achieve this. I could not have come this far without such a first-class supervisor. To my co-supervisor Yue Huang, your passion for MSA pushed me to search for more and you always helped me to think from a different perspective. I have learnt many things from you and I thank you for your support. My dearest friend and lab manager Heather, your meticulous training and perfectionism in the lab and has helped me to achieve this much. Thank you for your technical guidance, I have the deepest regard for you, both as a teacher and friend.
  • A Secret That Underlies Parkinson's Disease the Damaging Cycle

    A Secret That Underlies Parkinson's Disease the Damaging Cycle

    Neurochemistry International 129 (2019) 104484 Contents lists available at ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/neuint A secret that underlies Parkinson's disease: The damaging cycle T Feiyi Suna, Yulin Denga, Xiaowei Hanb,c, Qingqing Liua,1, Peng Zhanga, Robina Manzoora, ∗ Hong Maa, a School of Life Science, Beijing Institute of Technology, Beijing, 100081, China b Department of Radiology, Heping Hospital Affiliated with Changzhi Medical College, Changzhi, 046000, China cGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, 100730, China ARTICLE INFO ABSTRACT Keywords: Parkinson's disease (PD) is a movement disorder, and its common characteristics include the loss of dopami- Parkinson's disease nergic neurons and the accumulation of a special type of cytoplasmic inclusions called Lewy bodies in the Oxidative stress substantia nigra pars compacta, which are more prevalent in the elderly. However, the pathophysiology of PD is Endogenous neurotoxins still elusive. In this review, we summarized five common factors involved in PD, namely, (i) oxidative stress, (ii) Inflammation mitochondrial dysfunction, (iii) inflammation, (iv) abnormal α-synuclein, and (v) endogenous neurotoxins, and α-Synuclein aggregation proposed a hypothesis involving a damaging cycle. Oxidative stress-triggered aldehydes react with biogenic Damaging cycle amines to produce endogenous neurotoxins. They cause mitochondrial dysfunction and the formation of in- flammasomes, which induce the activation of neuroglial cells and the infiltration of T lymphocytes. Thesy- nergistic effect of these processes fosters chronic inflammation and α-synuclein aggregation and furtherex- acerbates the impact of oxidative stress to establish a damaging cycle that eventually results in the degeneration of dopaminergic neurons.
  • Recent Advances in Mass Spectrometry for the Identification of Neuro-Chemicals and Their Metabolites in Biofluids

    Recent Advances in Mass Spectrometry for the Identification of Neuro-Chemicals and Their Metabolites in Biofluids

    Send Orders for Reprints to [email protected] 436 Current Neuropharmacology, 2013, 11, 436-464 Recent Advances in Mass Spectrometry for the Identification of Neuro- chemicals and their Metabolites in Biofluids Suresh Kumar Kailasaa and Hui-Fen Wub,c,d,e,* aDepartment of Applied Chemistry, S. V. National Institute of Technology, Surat – 395007, India; bDepartment of Chemistry, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan; cSchool of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 800, Kaohsiung, Taiwan; dCenter for Nanoscience and Nanotechnology, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan; eDoctoral Degree Program in Marine Biotechnology, National Sun Yat- Sen University, Kaohsiung 80424, Taiwan Abstract: Recently, mass spectrometric related techniques have been widely applied for the identification and quantification of neurochemicals and their metabolites in biofluids. This article presents an overview of mass spectrometric techniques applied in the detection of neurological substances and their metabolites from biological samples. In addition, the advances of chromatographic methods (LC, GC and CE) coupled with mass spectrometric techniques for analysis of neurochemicals in pharmaceutical and biological samples are also discussed. Keywords: Neurochemicals, LC-MS, GC-MS, CE-MS, MALDI-MS. INTRODUCTION medical examinations. Few drugs (TCAs) inhibit the reuptake of norepinephrine (desipramine, nortriptyline, and Neuroscience is the subject to study the chemical protriptyline secondary amines) and serotonin (amitriptyline, composition and processes of the nervous system, which imipramine, clomipramine, and doxepine tertiary amines) in includes the brain, the spinal cord and the nerves and the the central nervous system [2-4]. In order to detect their effects of chemicals on them. As with all the senses, our concentration from human fluids, tandem mass spectrometry perception of outside world is processed by the peripheral has been widely used for sensitive identificaiton and and central nervous systems.
  • Salsolinol, a Derivate of Dopamine, Is a Possible Modulator of Catecholaminergic Transmission: a Review of Recent Developments

    Salsolinol, a Derivate of Dopamine, Is a Possible Modulator of Catecholaminergic Transmission: a Review of Recent Developments

    Physiol. Res. 55: 353-364, 2006 MINIREVIEW Salsolinol, a Derivate of Dopamine, is a Possible Modulator of Catecholaminergic Transmission: a Review of Recent Developments B. MRAVEC Institute of Experimental Endocrinology, Slovak Academy of Sciences and Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic Received May 31, 2005 Accepted August 17, 2005 On-line available October 17, 2005 Summary Catecholamine (dopamine, norepinephrine and epinephrine) synthesizing neurons are widely distributed in the brain, sympathetic ganglia and throughout peripheral organs. Results of several recent experiments clearly suggest that many of these neurons can also contain 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), a derivate of dopamine. However, direct proof of salsolinol synthesis in those neurons is still missing. The data obtained with administration of exogenous salsolinol strongly indicate that it may play an important role in catecholaminergic regulatory processes, such as the regulation of prolactin release and/or neuronal transmission in sympathetic ganglia. Several recent data have also indicated a relationship between salsolinol or its metabolites and the etiology of Parkinson's disease or neuropathology of chronic alcoholism. These seemingly different roles of salsolinol will be discussed separately, but some common features will also be highlighted. Based on all of the discussed data the existence of a “salsolinolergic” system using salsolinol as a neuromodulator, which may be present in catecholamine synthesizing neurons, is postulated. Key words Salsolinol • Dopamine • Prolactoliberin • Parkinson’s disease • 1MeDIQ Introduction Nobel Prize in 2000 (Carlsson 2001). The brain dopaminergic system is implicated in a variety of The neurotransmitters dopamine, norepinephrine physiological and pathophysiological processes.