Paper Information

Journal:   IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)   May 2004 , Volume 3 , Number Supplement 1; Page(s) 6 To 6.
 
Paper: 

GLOBAL GENE EXPRESSION ANALYSIS USING MICROARRAY TO STUDY DIFFERENTIAL VULNERABILITY TO NEURODEGENERATION

 
 
Author(s):  RAVINDRANATH V.*
 
* Manesar-122050, INDIA
 
Abstract: 

Neurodegenerative disorders such as Parkinson’s disease, motor neuron disease and Alzheimer’s disease is characterized by loss of specific cells within certain regions of the brain. One of the most compelling questions is to determine why specific cell populations are vulnerable to neurodegeneration. We addressed this question by studying global gene expression changes using an animal model of neurodegenerative disease. Human ingestion of “chickling peas” from the plant Lathyrus sativus containing an excitatory amino acid, L-b-N-oxalyl amino-L-alanine (L-BOAA) leads to a neurodegenerative disorder, neurolathyrism, a motor neuron disease characterized by spastic paraparesis that targets Betz cells in motor cortex (MC) and the anterior horn cells in the lumbosacral cord (LSC). Our laboratory has earlier shown that L-BOAA toxicity in mice is associated with mitochondrial dysfunction seen as loss of complex I activity in MC and LSC. While MC recovers after an initial insult, sustained injury is seen in LSC. We therefore, profiled global gene expression changes by microarray analyses in mice CNS regions during recovery from L-BOAA toxicity. Mouse cDNA arrays were hybridised with RNA from MC and LSC of control and L-BOAA treated mice. Data was analysed using Array vision and Spot-fire software. In concurrence with earlier results glutaredoxin, a thiol disulfide oxidoreductase was upregulated in both MC and LSC. Glutaredoxin is required for maintenance of complex I function. However, the up-regulation of NADH dehydrogenase (Complex I) was seen only in MC and not in LSC in agreement with the activity of complex I seen earlier. Upregulation of genes related to energy metabolism, antioxidant enzymes, MAP kinases and ubiquitin proteasomal pathways was seen in MC indicating their potential role in the recovery. In contrast in LSC, genes related to MAP kinases and anti-oxidant were not upregulated, instead programmed cell death gene was upregulated. These studies demonstrate the differential responses of CNS regions to a common excitotoxic insult and help identify factors responsible for differential vulnerability of CNS regions often seen in neurodegenerative diseases.

 
Keyword(s): 
 
References: 
  • ندارد
 
  Yearly Visit 29
 
Latest on Blog
Enter SID Blog