Accession Number : ADA434851


Title :   Mechanism for Prenatal LPS-Induced DA Neuron Loss


Descriptive Note : Annual rept. 1 Mar 2004-28 Feb 2005


Corporate Author : RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER CHICAGO IL


Personal Author(s) : Carvey, Paul M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a434851.pdf


Report Date : Mar 2005


Pagination or Media Count : 46


Abstract : A small percentage of patients with Parkinson's disease (PD) are caused by genetic defects (familial Parkinson's disease). The etiologies of the majority of patients are still unknown. Recent advance in our laboratories suggests that prenatal exposure to 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 normal number of dopamine (DA) neuron in the midbrain, a hall marker pathology in human patients. The mechanism for such DA neuron loss is not known. The preliminary data suggested that prenatal LPS may interfere DA neuron precursor cells (progenitor cells) migration to substantia nigra or DA neuron process outgrowth and therefore reduce the number of DA neurons in the midbrain. We proposed to use both in vivo and in vitro approaches to investigate these possibilities. A significant progress has been made in the last eleven months. Implementation of this proposal has resulted in three major findings: 1. Prenatal bacterial LPS induce loss of BrdU positive cells in the midbrain. 2. The toxicity of prenatal LPS requires removal of mitotic signal(s) to the dividing progenitor (stem) cells. 3. Prenatal LPS reduced dopamine neuron process total length that prevents dopamine neurones to reach trophic-rich striatal target tissue, a positive mechanism underlying the dopamine neuron loss in the prenatal LPS model.


Descriptors :   *BRAIN , *MOLECULES , *PRECURSORS , *BACTERIAL TOXINS , *DOPAMINE , *ETIOLOGY , *STEM CELLS , *PRENATAL DIAGNOSIS , *PARKINSONS DISEASE , IN VITRO ANALYSIS , MARKERS , IN VIVO ANALYSIS , CYTOKINES , CELLS(BIOLOGY) , GENETICS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE