The substantia nigra, pars compacta (SNc) is a structure that modulates voluntary motor control, and the death of the dopaminergic neurons in the SNc leads to many of the classic motor deficits associated with the Parkinson's disease (PD). Most conventional treatments alleviate symptoms but do not prevent the eventual death of neurons in the SNc. While fetal tissue transplant and stem cell therapy serve to replace lost cells, incomplete knowledge on dopamine neuron development within the SNc has limited the effectiveness of these treatments as most cells in the transplant fail to survive. Elucidating the factors that modulate dopamine neural development could lead to novel treatment approaches or increase the effectiveness of these replacement therapies in PD. In the rat brain, progesterone receptors (PRs) are expressed transiently in the perinatal SNc, suggesting a role for this hormone in the development of this region. Dr. Mennella proposes to characterize the temporal expression pattern of progesterone receptors in the mouse substantia nigra and determine their roles in the morphological and phenotypic development of that region. She also proposes to use PR knock-out (PRKO) mice to determine if absence of PRs during development leads to greater dopaminergic cell loss in the adult SNc, and more immature projections into the straitum, the primary recipient of SNc dopamine projections and greater motor deficits in adulthood.

Public Health Relevance

Parkinson's disease (PD) is a devastating age-related movement disorder caused by the progressive death of brain cells. Identifying factors that contribute to the disease could aid in prevention and cessation of the disease. Developmental abnormalities in the brain may confer susceptibility to PD. Exposure to the hormone progesterone during development could protect the brain against the onset of PD.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103653-03
Application #
8731949
Study Section
Special Emphasis Panel (ZRR1-RI-4)
Project Start
Project End
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
3
Fiscal Year
2014
Total Cost
$1,090,270
Indirect Cost
$62,593
Name
Delaware State University
Department
Type
DUNS #
114337629
City
Dover
State
DE
Country
United States
Zip Code
19901
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