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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS019608-09
Application #
3099749
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1983-07-01
Project End
1996-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Arts and Sciences
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Jaumotte, Juliann D; Wyrostek, Stephanie L; Zigmond, Michael J (2016) Protection of cultured dopamine neurons from MPP(+) requires a combination of neurotrophic factors. Eur J Neurosci 44:1691-9
Ayadi, Amina El; Zigmond, Michael J; Smith, Amanda D (2016) IGF-1 protects dopamine neurons against oxidative stress: association with changes in phosphokinases. Exp Brain Res 234:1863-1873
Napier, T Celeste; Corvol, Jean-Christophe; Grace, Anthony A et al. (2015) Linking neuroscience with modern concepts of impulse control disorders in Parkinson's disease. Mov Disord 30:141-9
Zigmond, Michael J; Smeyne, Richard J (2014) Exercise: is it a neuroprotective and if so, how does it work? Parkinsonism Relat Disord 20 Suppl 1:S123-7
Jaumotte, Juliann D; Zigmond, Michael J (2014) Comparison of GDF5 and GDNF as neuroprotective factors for postnatal dopamine neurons in ventral mesencephalic cultures. J Neurosci Res 92:1425-33
Ahrens, Allison M; Nobile, Cameron W; Page, Lindsay E et al. (2013) Individual differences in the conditioned and unconditioned rat 50-kHz ultrasonic vocalizations elicited by repeated amphetamine exposure. Psychopharmacology (Berl) 229:687-700
Zigmond, Michael J; Cameron, Judy L; Hoffer, Barry J et al. (2012) Neurorestoration by physical exercise: moving forward. Parkinsonism Relat Disord 18 Suppl 1:S147-50
Cohen, Ann D; Zigmond, Michael J; Smith, Amanda D (2011) Effects of intrastriatal GDNF on the response of dopamine neurons to 6-hydroxydopamine: time course of protection and neurorestoration. Brain Res 1370:80-8
El Ayadi, Amina; Zigmond, Michael J (2011) Low concentrations of methamphetamine can protect dopaminergic cells against a larger oxidative stress injury: mechanistic study. PLoS One 6:e24722
Allen, Erika; Carlson, Kirsten M; Zigmond, Michael J et al. (2011) L-DOPA reverses motor deficits associated with normal aging in mice. Neurosci Lett 489:1-4

Showing the most recent 10 out of 16 publications