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Factors affecting the extent of dopamine cell loss and behavioral sparing after partial unilateral lesions of the nigrostriatal dopamine pathway : the role of basic fibroblast growth factor

Title:

Factors affecting the extent of dopamine cell loss and behavioral sparing after partial unilateral lesions of the nigrostriatal dopamine pathway : the role of basic fibroblast growth factor

Moroz, Isabella Anna (2003) Factors affecting the extent of dopamine cell loss and behavioral sparing after partial unilateral lesions of the nigrostriatal dopamine pathway : the role of basic fibroblast growth factor. PhD thesis, Concordia University.

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Abstract

In this thesis, the hypothesis that endogenous expression of basic fibroblast growth factor (FGF-2), a neurotrophic and neuroprotective factor produced by astrocytes and shown to mediate behavioral sensitization to amphetamine, plays a role in behavioral recovery after 6-hydroxydopamine (6-OHDA) lesions of nigrostriatal dopamine neurons was studied. Initial findings revealed that, despite the increases in FGF-2 expression after lesions, there was a progressive loss of tyrosine hydroxylase immunoreactive (TH-IR) cells in the dopamine cell body regions and no behavioral recovery. Manipulations of gonadal hormones in the neonatal and adult life, known to enhance behavioral sensitization to amphetamine, reduced both the lesion-induced increases in astrocytic FGF-2 expression and losses in TH-IR cells in the dopamine cell body regions, but had no effect on behavioral recovery. Paradoxically, forced limb-use, shown previously and here to stimulate sparing after 6-OHDA lesions, did not further enhance lesion-induced increases in FGF-2, and did not protect against loss of TH-IR cells, but, in itself, increased FGF-2 expression. Finally, pre-lesion treatment with a sensitizing regimen of amphetamine, known to increase FGF-2 expression in the vicinity of dopamine neurons, led to remarkable sparing of function after subsequent lesions, but did not protect against loss of striatal tissue dopamine. It is proposed that the increases in endogenous expression of astrocytic FGF-2 seen here after extensive 6-OHDA lesions reflect a magnitude-dependent response of dopamine neurons to degeneration. These increases in FGF-2 may be effective in promoting recovery when combined with behavioral demands, such as forced use, or when induced before the injury

Divisions:Concordia University > Faculty of Arts and Science > Psychology
Item Type:Thesis (PhD)
Authors:Moroz, Isabella Anna
Pagination:xvii, 235 leaves : ill. ; 29 cm.
Institution:Concordia University
Degree Name:Theses (Ph.D.)
Program:Psychology
Date:2003
Thesis Supervisor(s):Stewart, Jane
ID Code:2139
Deposited By:Concordia University Libraries
Deposited On:27 Aug 2009 13:25
Last Modified:08 Dec 2010 10:24
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