GORDON CONFERENCE--CATECHOLAMINES
Michael J Zigmond, Professor
Gordon Research Conferences
west Kingston, Ri 02892
Grant 1R13NS031629-01 from National Institute Of Neurological Disorders And Stroke IRG: NSPB
Abstract: Funds are requested to provide partial support for a conference to be entitled. "Catecholamines From Molecule to Mind" and to be held in July, 1993. The conference will be organized with the assistance of the Gordon Research Conferences organization. The 5-day meeting will involve 100-125 people and will focus on a wide variety of topics relevant to our understanding of catecholamines, dealing with issues at the molecular, cellular, and organismal level. It will include information from both basic and clinical science. Among the unique features of the conference will be (1) the interdisciplinary nature of each session, (2) the large amount of time set aside for informal discussion, (3) the commitment of each participant to active participation in all aspects of the entire conference, and (4) the emphasis placed on obtaining a diverse group of participants, from the standpoint of institution, geographical location, level of achievement, gender, and minority status
Keywords: catecholamine, meeting /conference /symposium, neurotransmitter travel
Project start date: 1993-04-01
Project end date: 1994-03-31
1R13NS031629-01 (1993): $38000
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Michael J Zigmond
Training In The Neurobiology Of Neurodegenerative Dise
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5T32NS007391-10 from National Institute Of Neurological Disorders And Stroke IRG: NST
Abstract: We request continuing support for this postdoctoral training program in basic neuroscience as it relates to neurodegenerative disease and stroke. The program is closely integrated with several key research programs related to Parkinson s disease, Alzheimer s disease, ALS, and stroke. Additional programs in psychiatric disorders and in neuroAIDS further enhance the environment. The grant will permit us to maintain the critical mass needed to recruit the best possible postdoctoral trainees, including under represented minority trainees, and to offer a training program of the highest quality. Our training program focuses primarily on basic and translational laboratory research that can readily be related to neurodegenerative disease and stroke. The major research advisor and an individualized research advisory committee, a professional development committee, and the training grant steering committee share the task of guiding and monitoring each trainee. All trainees participate in three activities which supplement their research experience (1) Two seminars on the neurobiology of clinical disorders, (2) a monthly research discussion, and (3) a series of professional development workshops. Issues of responsible conduct are integrated into the entire program. Trainees also participate in courses as needed and have opportunities to teach and to observe clinical practice. The 39 members of the training faculty are members of the university-wide program in neuroscience with a particular interest in neurodegenerative disorders and stroke. Most of the faculty members have extensive experience in training and in research and have significant grant support. In addition, we have included a small group of junior faculty who have outstanding promise and will be available to serve as co-mentors in conjunction with a more senior faculty member. At present our training faculty supervise more than 90 postdoctoral trainees (in addition to a large number of predoctoral students), of whom about 20 are eligible for NRSA support. We are requesting stipends to support an initial complement of 4 postdoctoral trainees, increasing gradually to 8 over a 5-year period. We believe that our training program provides an opportunity for outstanding postdoctoral trainees to prepare for a career of direct relevance to issues of neurodegenerative disease and stroke.
Project start date: 1997-07-01
Project end date: 2008-06-30
5T32NS007391-10 (2006): $179457
5T32NS007391-09 (2005): $211384
5T32NS007391-08 (2004): $11384
2T32NS007391-06 (2002): $184997
Training In The Neurobiology Of Psychiatric Disorders
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5T32MH018273-22 from National Institute Of Mental Health IRG: ZMH1
Abstract: We request continuing support for postdoctoral training in basic neuroscience related to psychiatric disorders. Our program is closely integrated with several key research programs related to cognition and schizophrenia, developmental disorders, mood and depression, and the dementia associated with Alzheimer s disease, and AIDS. Additional programs in neurodegenerative disease, stroke, and basic neuroscience further enhance the environment. In our program, the major research advisor, an individualized advisory committee, and the training grant steering committee share the task of guiding and monitoring each trainee. The training program (1) focuses on mentored research, but includes (2) a seminar on the neurobiology of psychiatric and neurological disorders, (3) a monthly research discussion, (4) an annual trainee retreat, and (5) a professional development program. In addition, (6) discussion of issues of the responsible conduct of research occurs throughout the program. Moreover, (7) trainees also participate in courses as needed and have opportunities to (8) teach and (9) observe clinical practice. The 31 members of the training faculty are members of the university-wide program in neuroscience with a particular interest in the neurobiology of psychiatric disorders and affiliated with several academic departments and programs. All 20 full members of the faculty have active, funded research programs and training experience research. In addition, we have included 8 more junior faculty with outstanding promise who will be available to serve as co-mentors in conjunction with a more senior faculty member. We are requesting stipends to support an initial complement of 4 postdoctoral trainees, increasing to 6 after 2 years. These stipends will be used to support trainees for up to two years, although all trainees will be required to apply for their own fellowships within 6 mo of beginning our program and this should make available funds for other individuals. We believe that our program will increase the capacity for translational research of relevance to the NIMH mission.
Project start date: 1985-07-01
Project end date: 2011-06-30
5T32MH018273-22 (2007): $120932
2T32MH018273-21A1 (2006): $139930
5T32MH018273-25 (2010): $130771
5T32MH018273-24 (2009): $150553
5T32MH018273-23 (2008): $145971
TRAINING IN THE NEUROBIOLOGY OF NEURODEGENERATIVE DISEASE
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh, Office Of Research, Pittsburgh, Pa 15213
Grant 5T32NS007391-13 from National Institute Of Neurological Disorders And Stroke
Abstract: We request continuing support for our postdoctoral training program in basic neuroscience as it relates to neurodegenerative disease and stroke. The program is closely integrated with several key research programs related to Parkinson´s disease, Alzheimer´s disease, ALS, and stroke, and to the Pittsburgh Institute for Neurodegenerative Diseases, now housed in contiguous space within a newly constructed state-of-the-art facility. Additional programs in psychiatric disorders and in neuro-AIDS further enhance the environment. The grant will permit us to maintain the critical mass needed to recruit the best possible postdoctoral trainees, including underrepresented minority trainees, and to offer a training program of the highest quality. Our training program focuses primarily on basic and translational laboratory research that can readily be related to neurodegenerative disease and stroke. The major research advisor and an individualized research advisory committee and the training grant steering committee share the task of guiding and monitoring each trainee. All trainees participate in four activities that supplement their research experience 1) A seminars on the neurobiology of clinical disorders, 2) a monthly research discussion, 3) a series of professional development workshops, and 4) at least one outreach activity. Issues of responsible conduct are integrated into the entire program. Trainees also participate in courses as needed and have opportunities to teach and to observe clinical practice. The 33 members of the training faculty are members of the university-wide program in neuroscience with a particular interest in neurodegenerative disorders and stroke. Most of the faculty members have extensive experience in training and in research and have significant grant support. In addition, we have included a group of 9 junior faculty who have outstanding promise and will be available to serve as co-mentors in conjunction with a more senior faculty member. At present our training faculty supervise more than 90 postdoctoral trainees (in addition to a large number of pre-doctoral students), of whom about 20 are eligible for NRSA support. We are requesting stipends to support an initial complement of 4 postdoctoral trainees, increasing gradually to 6 over a 5-year period. We believe that our training program provides an opportunity for outstanding postdoctoral trainees to prepare for a career of direct relevance to issues of neurodegenerative disease and stroke
Keywords: Degenerative Diseases, Nervous System; Degenerative Neurologic Disorders; Neurobiology; Neurodegenerative Diseases; Neurodegenerative Disorders; Neurologic Degenerative Conditions; Neurologic Diseases, Degenerative; Training; neurobiological; neurodegenerative illness
Project start date: 1997-07-01
Project end date: 2013-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-06-468
5T32NS007391-13 (2010): $203463
Sponsored Links Excellgen http://Excellgen.com
3T32NS007391-13S1 (2010): $58655
5T32NS007391-12 (2009): $300555
2T32NS007391-11A1 (2008): $259138
STRESS & MONOAMINES--NEUROPHYSIOLOGY & NEUROCHEMISTRY
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5R01MH043947-05 from National Institute Of Mental Health IRG: SRCM
Abstract: We propose to examine the impact of acute and chronic stress on the functional capacity of central noradrenergic neurons. Our studies may be divided into three groups. (1) We wish to determine whether changes in tyrosine hydroxylase (TH) activity within locus coeruleus (LC) neurons during chronic cold stress are indicative of alterations in norepinephrine (NE) efflux. Release will be monitored using in vitro slices, in vivo voltammetry, and local perfusion in situ via dialysis tubing. The LC and two of its terminal fields will be examined, cerebellum and hippocampus will be examined. Among the questions to be studied are the following Does acute, severe stress lead to an initial depletion of releasable NE? Does the activation of TH, which occurs within a few minutes of stimulation, increase the capacity for subsequent release? Does TH induction lead to a still greater capacity for release? (2) We wish to determine the extent to which increases in NE release during stress are due to alterations in the firing rate of LC neurons. We will record from LC neurons and determine the impact of stress on the firing rate of these cells. In addition, we will measure the amount of transmitter released from slices per impulse. (3) We wish to determine the degree to which adaptive changes occurring in central NE neurons in response to chronic stress affect the functioning of post-synaptic cells. We will record from single hippocampal granule cells and cerebellar Purkinje neurons during electrical stimulation of the LC to determine if exposure to chronic stress alters the inhibitory effect of release of endogenous NE on the spontaneous firing rates of these target neurons. In addition, electrical stimulation of glutaminergic, perforant path input to granule cells during electrical stimulation of the LC will be used to determine if exposure to chronic stress alters the modulatory effect of NE on other, non-NE inputs to target neurons. This work will be related to the basic neurobiology of monoaminergic neurons and their targets and to the relation between stress and depression.
Keywords: locus coeruleus, neurochemistry, neurophysiology, stress, adrenergic receptor, cerebellar Purkinje s cell, cerebellum, cold temperature, environmental stressor, enzyme mechanism, hippocampus, neurotransmitter metabolism, norepinephrine, tyrosine 3 monooxygenase, electrophysiology, electrostimulus, laboratory rat
Project start date: 1988-06-01
Project end date: 1993-05-31
5R01MH043947-05 (1992): $173087
TRAINING IN NEUROBIOLOGY OF NEURODEGENERATIVE DISEASE
Michael J Zigmond, Professor
Neurologyuniversity Of Pittsburgh At Pittsburgh
350 Thackeray Hall
pittsburgh, Pa 15260
Grant 5T32NS007391-05 from National Institute Of Neurological Disorders And Stroke IRG: NST
Abstract: This revised application requests funds to initiate a new predoctoral and postdoctoral training program in basic neuroscience as it relates to neurodegenerative disease. The program will build on existing training programs, an NINDS-funded Program Project on basal ganglia and parkinsonism headed by the program Director of this application. These training and research programs have already helped to develop and integrate diverse elements of the basic neuroscience community at the University of Pittsburgh and to strengthen its ties to clinical neuroscience. If funded, the addition of pre- and postdoctoral positions provided by NINDS would provide the critical mass needed to recruit the best possible pre- and postdoctoral students (including underrepresented minority students) and to offer a training program of the highest quality. Our proposed program focusses primarily on research training. However, predoctoral students will take a series of core courses in neuroscience and other areas of basic biological science, a course in clinical neuroscience, and advanced seminars, and pass through a series of "milestones," including a comprehensive exam. Postdoctoral trainees will attend courses and seminars as needed. In addition, both groups will participate actively in a series of professional development workshops. These workshops provide explicit training in such "survival skills" as written and oral communication, obtaining jobs and grants, teaching and managing a research lab. Training in responsible conduct is an integral part of both the survival skill workshops and the core curriculum itself. Students are encouraged to consider a wide range of employment opportunities within which to exercise their skills in research and seminars are held to permit them to become familiar with employment both within and outside of traditional academic research universities. Members of the training faculty come primarily from the Department of Neuroscience. Other participating departments and centers include the Departments of Neurobiology, Neurology, Pathology, and Pharmacology, Psychiatry, and the Center for Neuroscience. Two groups of faculty are described a core group of full faculty , consisting of individuals with extensive experience in training and in research, and a small group of "pro- faculty" who have outstanding promise and will be available to serve as co-mentors in conjunction with a more senior faculty member. Data are provided to support our belief that we will be able to obtain outstanding trainees for the proposed program
Project start date: 1997-07-01
Project end date: 2002-06-30
5T32NS007391-05 (2001): $162355
5T32NS007391-04 (2000): $150902
5T32NS007391-03 (1999): $147624
1T32NS007391-01A2 (1997): $227845
NEUROBIOLOGY OF THE INTACT AND DAMAGED BASAL GANGLIA
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5P01NS019608-10 from National Institute Of Neurological Disorders And Stroke IRG: NSPA
Abstract: This Program Project will explore the neurochemistry, electrophysiology, and anatomy of the basal ganglia after damage to the dopamine (DA) containing neurons of the nigrostriatal bundle (NSB). The neurotoxin 6-hydroxydopamine will be administered intracerebrally to adult rats to produce an animal model of Parkinson s disease. Among the issues to be examined are the neurobiological basis of the extensive pre-clinical phase of this disorder and of the impact of stress on parkinsonian symptoms. Possible modes of therapy in the treatment of the disease also will be studied. As part of this endeavor, a multi-disciplinary characterization of many aspects of the normal basal ganglia will be required. Included in this characterization will be an examination of the interactions among dopaminergic, cholinergic, glutamatergic, and GABAergic neurons and an in-depth study of the molecular biology of the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH). It is expected that these studies will provide insights into the relation between neuropathology and symptomatology in a variety of neurodegenerative disorders, be of value in developing new modes of therapy for these conditions, and add important new information concerning the neurobiology of the basal ganglia.
Keywords: basal ganglia, dopamine, neural plasticity
Project start date: 1983-07-01
Project end date: 1996-06-30
5P01NS019608-10 (1992): $981643
5P01NS019608-11 (1993): $975480
Sponsored Links Excellgen http://Excellgen.com
5P01NS019608-18 (2001): $1011699
5P01NS019608-17 (2000): $964629
3P01NS019608-17S1 (2000): $100000
3P01NS019608-16S1 (1999): $75650
5P01NS019608-16 (1999): $852747
2P01NS019608-14A1 (1997): $630821
NEUROBIOLOGY OF ADAPTATION TO STRESS AND INJURY
Michael J Zigmond, Professor
Neurologyuniversity Of Pittsburgh At Pittsburgh
350 Thackeray Hall
pittsburgh, Pa 15260
Grant 5K05MH000058-25 from National Institute Of Mental Health IRG: NPNC
Abstract: This is a renewal application for a Research Scientist Award to permit me to continue my research program with its associated training ofjunior investigators, and to coordinate a large multi-lab research endeavor. Research Program My group is interested in the pre- and post-synaptic biochemical events associated with adaptation to altered neuronal activity, as well as the functional significance of this neuroplasticity. The work focuses on systems that utilize catecholamines. The work can be divided into three interrelated programs the biological bases of degeneration and compensation in an animal model of parkinsonism; the consequences of chronic stress on transmitter synthesis and release; and regulation of dopaminergic activity in subcortical regions by cortical input. In this application, I focus on the first of these programs, which has long been the central theme of our research and the focus of my previous applications providing a Research Scientist Award. I emphasize five specific aims designed to determine (l) the extent to which function is preserved after damage to the dopaminergic input to neostriatum, (2) the generality of our model for compensations after partial lesions, looking at other conditions of hypoinnervation including aging, (3) the neurobiological bases for the discrepancies between terminal loss and functional deficits, (4) the neurotoxic consequences of increased dopaminergic activity, and (5) the extent to which tyrosine hydroxylase can be transferred into non-dopaminergic cells to effectively restore dopaminergic activity after extensive neurodegeneration. I believe these studies will provide basic information on the neurobiology of neuronal interactions as well as insights into aspects of several neurological and psychiatric disorders. Research Administration My lab is composed of about a dozen individuals, including pre- and post-doctoral trainees, senior research associates, and staff. The work is coordinated through weekly "working group" meetings, biweekly lab-wide meeting, and meetings of the administrative and research staff. I also direct two inter-lab research projects involving eight other faculty members and members of their groups. Mentoring A considerable amount of time is devoted to mentoring members of the lab group. This occurs through regular group meetings as well as individual meetings. Much of the day-to-day supervision of the graduate students occurs through the more senior members of the group. Training I direct an NIMH-funded training program in basic neuroscience. As part of this effort I run a series of monthly, day-long workshops in areas of professional development and ethics, and participate in a summer training program at the Marine Biological Lab (Woods Hole, MA) for minority students in neuroscience
Keywords: dopamine, neural degeneration, neural plasticity, neurochemistry Parkinson`s disease, acetylcholine, aging, corpus striatum, cyclic AMP, developmental neurobiology, disease /disorder model, dopamine receptor, gamma aminobutyrate, gene expression, genetic transduction, glutamate, neural transmission, neurotoxicology, neurotransmitter metabolism, neurotransmitter transport, tyrosine 3 monooxygenase 6 hydroxydopamine, experimental brain lesion, in situ hybridization, laboratory rat
Project start date: 1991-04-01
Project end date: 2001-03-31
5K05MH000058-25 (2000): $101007
5K05MH000058-24 (1999): $101007
5K05MH000058-22 (1997): $109350
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 2P01NS019608-159004 from National Institute Of Neurological Disorders And Stroke
Abstract: This Core provides neurochemical analyses for members of the Program Project. In particular it analyzes the dopamine (DA) content of tissue taken from 6-OHDA-treated animals as a means of quantifying the impact of the lesion. Other assays available include that for serotonin, tyrosine hydroxylase activity, and protein. Additional analytical procedures will be developed as necessary.
Keywords: analytical chemistry, biomedical facility, dopamine, neurochemistry, aromatic L aminoacid decarboxylase, enzyme activity, serotonin, tyrosine 3 monooxygenase, aminoacid analyzer, high performance liquid chromatography, tissue /organ preservation
Sponsored Links Excellgen http://Excellgen.com
PREDOCTORAL TRAINING IN BASIC NEUROSCIENCE
Michael J Zigmond, Professor
Neurologyuniversity Of Pittsburgh At Pittsburgh
350 Thackeray Hall
pittsburgh, Pa 15260
Grant 5T32NS007433-04 from National Institute Of Neurological Disorders And Stroke IRG: ZNS1
Abstract: This application requests funds to initiate a new highly integrated predoctoral training program in basic neuroscience. The training grant will build on two existing training grants, "Training in the neurobiology of psychiatric disorders" (MH18273) and "Training in the neurobiology of neurological disorders" (NS07391). In addition, the training grant program will help to consolidate three neuroscience training programs within our community, those in the Department of Neuroscience, the Program in Neurobiology, and the Center for the Neural Bases of Cognition, programs that cut across two universities, the University of Pittsburgh and Carnegie Mellon University. Funds requested will be used to support students in their first and second years, with support being provided to the top one-third of our trainees. The program described within this proposal focuses primarily on research training. However, students will take a series of core courses in neuroscience and other areas of basic biological science, a course in clinical neuroscience, and several advanced elective courses and seminars, and will pass through a series of "milestones," including a comprehensive exam. In addition, trainees will participate actively in a series of professional development workshops. These workshops provide explicit training in such "survival skills" as written and oral communication, obtaining jobs and grants, teaching, and managing a research lab. Training in responsible conduct is an integral part of both the survival skill workshops and the core curriculum itself. Students are encouraged to consider a wide range of employment opportunities within which to exercise their skills in research, and seminars are held to permit them to become familiar with employment both within and outside of traditional academic research universities. Two groups of faculty are described a core group of full faculty, consisting of individuals with extensive experience in training and in research, and a small group of junior "pro-faculty" who have outstanding promise and will be available to serve as co-mentors in conjunction with a more senior faculty member. Data are provided to support our belief that we will be able to obtain outstanding trainees for the proposed program
Project start date: 1998-07-01
Project end date: 2003-06-30
5T32NS007433-04 (2001): $298064
5T32NS007433-03 (2000): $285811
TRAINING IN THE NEUROBIOLOGY OF PSYCHIATRIC DISORDERS
Michael J Zigmond, Professor
Neurologyuniversity Of Pittsburgh At Pittsburgh
350 Thackeray Hall
pittsburgh, Pa 15260
Grant 2T32MH018273-16 from National Institute Of Mental Health IRG: ZMH1
Abstract: This application requests funds to continue a training grant focusing on basic neurobiological studies of relevance to mental health, with a particular focus on issues of cell-cell communication. This program will build on a larger training program in neuroscience and on three major groups (1) stress and monoamines (supported by MH29670), (2) the Center for Neuroscience of Mental Disorders (supported by MH45156), and the neuroendocrine interest group with its affiliated Center for Research in Reproductive Physiology and Primate Center and a grant to support the Primate Center (supported by HD08610 and several R0-1 grants). These training and research programs have helped to develop and integrate diverse elements of the basic neuroscience community at the University of Pittsburgh and to strengthen its ties to clinical neuroscience. We wish to further develop our training in neuroscience by building on these accomplishments while adapting to the current needs of our community. In particular we wish to develop a training program that consolidates several groups of faculty with a primary interest in neurodegenerative disease. Predoctoral students take a series of core courses in neuroscience and other areas of basic biological science, a seminar on professional skills, and other advanced seminars. Postdoctoral trainees attend the professional skills seminar and other courses and seminars as needed. The majority of faculty mentors will be in the Department of Neuroscience in the Faculty of Arts and Sciences. Other participating departments and centers include the Center of Neuroscience, the Alzheimer´s Disease Research Center, and the Departments of Biological Sciences, Neurobiology, Cell Science and Physiology, Neurology, and Pathology
Project start date: 1985-07-01
Project end date: 2005-06-30
2T32MH018273-16 (2000): $205656
DEVELOPMENT STRESS, EXERCISE, AND VULNERABILITY TO NEURONAL INJURY
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh, Office Of Research, Pittsburgh, Pa 15213
Grant 5R01TW008040-04 from Fogarty International Center
Abstract: Researchers representing the University of Pittsburgh and two institutions in South Africa, the University of Cape Town and the University of Stellenbosch are seeking funds as part of an overall effort between our institutions to examine a specific hypothesis pertaining to the impact of environment on brain and behavior and also to help create within the academic community in Cape Town a regional center of excellence in neuroscience and in professional skill training. Their hypothesis is that exposure of developing animals to severe stress will have a significant detrimental effect on brain and increase its vulnerability to neuronal death, but that this can be offset through an exercise intervention program. There are five specific aims four are research aims and one is a set of capacity building objectives. Research objectives Aim 1 - To examine the impact of a developmental stressor (maternal separation) on several variables related to the vulnerability of the brain, including (a) the hypothalamic-pituitary-adrenal (HPA) axis, (b) mitochondrial function, and (c) alterations in a specific class of proteins (neurotrophic factors) by using a proteomic screen. Aim 2 - In addition, the state of central dopamine neurons will be carefully examined. Aim 3 - To examine the effects of exercise (voluntary running) on these same variables, and then to determine whether the effect of maternal separation can be offset by later exposure to exercise. Aim 4 -To examine the effects of maternal separation on the vulnerability of dopaminergic neurons to oxidative stress using 6- hydroxydopamine as the stressor, then determine whether any increase in vulnerability caused by the maternal separation can be offset by exercise. Aim 5 - Capacity building objectives To further develop the research capacity of the Universities of Cape Town and Stellenbosch as well as other institutions in the Western Cape through attendance by faculty and trainees at international meetings, participation in specific courses on research methodology, and provision of instruction in other professional skills, such as oral and written communication, applying for research funds, and responsible conduct of research. The research team believes that their research project will provide important insights into epigenetic influences on behavior and brain function more generally, and also serve as a context for promoting the research capacity of two key institutions in southern Africa
Keywords: 21+ years old; 5-(2-Aminoethyl)-1, 2, 4-benzenetriol; 6-Hydroxydopamine; 6-OHDA; ADRGND; Adrenal Glands; Adrenals; Adult; Africa, Southern; Animals; Behavior; Brain; Cessation of life; Communication; Communities; DA Neuron; Death; Development; Dopamine neuron; Dressing; Encephalon; Encephalons; Environment; Epigenetic; Epigenetic Change; Epigenetic Mechanism; Epigenetic Process; Equipment; Exercise; Exercise, Physical; Exposure to; Faculty; Funding; HPA; Human, Adult; Hypophysis; Hypophysis Cerebri; Hypothalamic structure; Hypothalamus; Institution; Instruction; International; Investigation; Investigators; Methodology, Research; Mitochondria; Nerve Cells; Nerve Unit; Nervous System, Brain; Nervous System, Pituitary; Neural Cell; Neurocyte; Neuronal Injury; Neurons; Neurosciences; Oral; Oxidative Stress; Oxidopamine; Perinatal; Pituitary; Pituitary Gland; Programs (PT); Programs [Publication Type]; Proteins; Proteomics; R01 Mechanism; R01 Program; RPG; Republic of South Africa; Research; Research Grants; Research Methodology; Research Methods; Research Personnel; Research Project Grants; Research Projects; Research Projects, R-Series; Researchers; Running; South Africa; Southern Africa; Sterile coverings; Stress; Testing; Toxic effect; Toxicities; Training; Union of South Africa; Universities; Writing; adult human (21+); brain behavior; design; designing; dopaminergic neuron; gene product; hypothalamic; hypothalamic-pituitary-adrenal (HPA) axis; hypothalamic-pituitary-adrenal axis; hypothalmus-pituitary-adrenal axis; insight; intervention program; maternal separation; meetings; mitochondrial; neuron injury; neuronal; neurotrophic factor; neurotrophin; neutrophin; programs; responsible research conduct; skills; skills training; stressor; suprarenal gland
Project start date: 2007-04-01
Project end date: 2011-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
PFA/PA: PAR-05-100
5R01TW008040-04 (2010): $200000
1R01TW008040-01A1 (2007): $200000
BIOCHEMISTRY OF BEHAVIORAL RECOVERY AFTER CNS DAMAGE
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5K05MH000058-19 from National Institute Of Mental Health IRG: MHK
Abstract: Parkinson s disease is associated with degeneration of the dopamine (DA)- containing neurons of the nigrostriatal bundle (NSB). However, the neurological symptoms that accompany this disease do not emerge until the degenerative process is almost complete. This phenomenon can be observed in a rat animal model of the disorder that is produced by the intracerebral administration of the selective neurotoxin 6-hydroxydopamine (6-HDA). Studies utilizing this model suggest that the capacity to withstand NSB injury is a consequence of increased synthesis and release of DA from those NSB neurons that remain together with a decrease in the rate at which that DA is inactivated. The experiments proposed in this application are designed to examine several aspects of this hypothesis, including the mechanism by which the hyperactivity might occur. Also to be examined are several aspects of the basic neurobiology of monoaminergic systems, including the interactions among neurotransmitters within striatum and the role of extracellular DA in these interactions. Findings from these studies may have important implications for the treatment of a, variety of neurological and psychiatric diseases, as well as our understanding of neuroplasticity in monoaminergic systems.
Keywords: brain injury, neurochemistry, Parkinson s disease, acetylcholine, corpus striatum, disease model, dopamine, dopamine receptor, extracellular, gamma aminobutyrate, glutamate, neural transmission, physiologic stressor, secretion, 6 hydroxydopamine, electrophysiology, histology, laboratory rat
Project start date: 1991-04-01
Project end date: 1996-03-31
5K05MH000058-19 (1994): $105174
5K05MH000058-17 (1992): $105174
Sponsored Links Excellgen http://Excellgen.com
Neuroprotection And Early Detection In PD
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5P50NS019608-23 from National Institute Of Neurological Disorders And Stroke IRG: NSD
Abstract: Parkinson s disease (PD) poses a serious threat to the health of a large segment of our society. This is an extensively revised renewal application for a Program Project Grant now in its 18th year. During much of the history of the PPG, we have focused on the compensatory changes that underlie the preclinical phase of PD. That line of investigation will continue, while at the same time we will also add two new foci first, the development of neuroprotective strategies and, second, the detection of PD it its preclinical phase. Neuroprotection This will now provide the principal long-term focus of the entire PPG. Our approach derives from recent evidence from our labs indicating that the contralateral motor neglect and loss of DA normally following unilateral damage to the nigrostriatal DA projection can be ameliorated by forced use of the contralateral limb. We hypothesize that forced execution of a motor act that is otherwise compromised by PD is neuroprotective, and that this results from an interaction between the motor act, injury, and concomitant increase in the availability of one or more trophic. We will explore this hypothesis using our 6-hydroxydopamine (6-OHDA) rat model. Our work will involve studies of the role of trophic factors (e.g., GDNF, BDNF, and FGF2), estrogen, and aging, as well as anatomical studies to differentiate between protection, rescue and sprouting (Project 1 M. Zigmond, PI). We also use multineuron recording in awake animals to examine the effect of forced use on the functioning of the basal ganglia more broadly (Project 2, D. Woodward, PI). Compensation In the past, our studies of compensation have focused our studies on adaptations within the nigrostriatal dopamine (DA) system. Our multineuron recordings will now allow us to explore adjustments within other components of the basal ganglia (Project 2 D. Woodward, PI). Early detection For neuroprotective strategies to be most effective, it is likely that they must be applied as early in the course of the disease as possible. In this respect, the compensatory changes noted above represent a problem to be overcome through the development of diagnostic tests that can detect PD before the emergence of gross neurological deficits. To do so we will develop a multi-dimensional clinical test battery, using PET imaging as the ultimate criteria for nigrostriatal damage (Project 3, N. Bohnen, PI). We believe that by combining a variety of basic, translational, and clinical approaches we will make significant progress toward the development of a therapeutic approach to PD.
Keywords: Parkinson s disease, biomarker, early diagnosis, neuroprotectant, clinical research
Project start date: 1983-08-01
Project end date: 2008-04-30
5P50NS019608-23 (2007): $1233642
5P50NS019608-22 (2006): $1254574
5P50NS019608-21 (2005): $1263361
5P50NS019608-20 (2004): $1248017
2P50NS019608-19A1 (2003): $1144290
USE AND DRUG DEPENDENT NEUROPROTECTION--TROPIC FACTORS
Michael J Zigmond, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5P50NS019608-230012 from National Institute Of Neurological Disorders And Stroke IRG: NSD
Abstract: Parkinson s disease (PD) poses a serious threat to the health of a large segment of our society. Having focused on the compensatory changes that underlie the preclinical phase of PD, we are now concentrating our efforts on the issue of neuroprotection. The present project is one component of this effort and focuses on strategies for inducing endogenous neuroprotective mechanisms in animal models of PD. The work derives from recent evidence from our labs indicating that the contralateral motor neglect normally following unilateral damage to the nigrostriatal dopamine (DA) projection can be ameliorated by forced use of the contralateral limb. Moreover, we find that this behavioral sparing is accompanied by a dramatic reduction in the loss of DA. We hypothesize that forced execution of a motor act that is otherwise compromised by PD is neuroprotective, and that this results from an interaction between the motor act, injury, and concomitant increase in the availability of one or more trophic factors (e.g., GDNF) and hormones (e.g. estrogen). Our project utilizes 6-hydroxydopamine (6-OHDA)-treated rodent models of PD and has five specific aims (1) We will determine the impact of forced use/disuse on the anatomical and functional state of DA neurons, including the use of microdialysis to measure in vivo DA efflux. (2) We will determine the relationship between use-dependent neuroprotection and increased trophic factor expression by using antisense oligonucleotides to reduce expression, fusion proteins to serve as decoys for the factors, and animals deficient in a protein key to trophic factor signaling. (3) We will examine the ability of estrogen to exert a neuroprotective influence and the possible role of that influence on the impact of exercise. (4) We will use microarrays together with more classical techniques to examine changes in other trophic factors and their receptors in striatum of animals subjected to lesions and/or casting. Later we will also look at substantia nigra and at regions where no neuroprotection is seen. (5) Finally, we will examine the impact of age on neuroprotection induced by trophic factors by first determining whether neuroprotection induced in young adult rats continues to be effective as animals reach old age, and then ask whether neuroprotective strategies that work in young adults can also be used to reduce the impact of 6-OHDA in aged rats.
Keywords: Parkinson s disease, dopamine, hormone regulation /control mechanism, limb movement, muscle function, neuroprotectant, neurotransmitter transport, neurotrophic factor, age difference, antisense nucleic acid, biological signal transduction, exercise, gender difference, gene expression, neuroanatomy, neurochemistry, neuromuscular system, neuron, behavior test, enzyme linked immunosorbent assay, in situ hybridization, laboratory mouse, laboratory rat, microarray technology, microdialysis, polymerase chain reaction
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