Accession Number : ADA462158


Title :   Mechanism for Prenatal LPS-Induced DA Neuron Loss


Descriptive Note : Final rept. 1 Mar 2004-31 Aug 2006


Corporate Author : RUSH UNIV MEDICAL CENTER CHICAGO IL


Personal Author(s) : Carvey, Paul M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a462158.pdf


Report Date : Sep 2006


Pagination or Media Count : 142


Abstract : In nonfamilial Parkinson's Disease (PD) the etiologies of the majority of patients are still unknown. However, recent advances by the authors suggest that prenatal exposure to the bacterial toxin lipopolysaccharide (LPS) could be an important etiology for some PD patients. A key finding is that animals exposed to LPS prenatally display fewer than the normal number of dopamine (DA) neurons in the midbrain, the hallmark of PD pathology in human patients. The mechanism for this DA neuron loss is unknown, but preliminary data suggest that prenatal LPS exposure may interfere with the migration of DA neuron precursor cells (progenitor cells) to the substantia nigra or with DA neuron process outgrowth, thereby reducing the number of DA neurons in the midbrain. The authors proposed to use both in vivo and in vitro approaches to investigate these possibilities. Significant progress has been made in the last 11 months. Implementation of this proposal has resulted in three major findings: (1) prenatal bacterial LPS exposure induces the loss of BrdU positive cells in the midbrain; (2) the toxicity of prenatal LPS exposure results in the removal of mitotic signal(s) to the dividing progenitor (stem) cells; and (3) prenatal LPS exposure reduces dopamine neuron process outgrowth, preventing dopamine neurons from reaching trophic-rich striatal tissues, a mechanism underlying the dopamine neuron loss in the prenatal LPS model.


Descriptors :   *ETIOLOGY , *NERVE CELLS , *EXPOSURE(PHYSIOLOGY) , *TERATOGENIC COMPOUNDS , *LIPOPOLYSACCHARIDES , *PARKINSONS DISEASE , *BACTERIAL TOXINS , TOXIC HAZARDS , RATS , IN VIVO ANALYSIS , CYTOKINES , STEM CELLS , MITOSIS , GROWTH(PHYSIOLOGY) , ENDOTOXINS , DOPAMINE , LOSSES , PATHOLOGY , MIGRATION , PHYSIOLOGICAL EFFECTS , IN VITRO ANALYSIS


Subject Categories : Biochemistry
      Medicine and Medical Research
      Toxicology
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE