Neuronal Sodium Channels in Neurodegeneration and Neuroprotection
Abstract
The purpose of this research project is to study the role of neuronal sodium channels in mechanisms of neuronal injury neurodegeneration, and neuroprotection. The primary objective of this research project is to characterize the expression, and study the functional significance, of neuronal sodium channels (hiring the process of injury and recovery. Also, the effects of sodium channel blockade (using antisense and channel blockers) on gene expression and neurodegeneration will be studies. The progress during our 3rd year of this project was excellent. Several important and critical discoveries providing a greater understanding of the injury/neurodegeneration process and the role of brain NAChs in this process were elucidated. Our key observations were 1) using ASO for the Nal .1 NaCh it was demonstrated that functional blockade of this channel results in brain neuroprotection following injury; 2) our in situ hybridization experiments defined the regional anatomical distribution of Nav1. 1 sodium channel gene expression in normal and at various time-post MCAo and confirmed our QRT-PCR data showing the Nal - 1 expression to be down-regulated in subcortical and cortical regions of injured and, to some degree of contralateral hemispheres. In addition, these in situ hybridization studies revealed that the expression of other NaCh gene appears not to be of significance to the brain injury process; 3) our preliminary results show that treatment of neurons with RS-1000642 at least partially reverses the down-regulation of Nav1. 1 caused by MCAo injury. Importantly, evidence eindicates that this is an effect selective for the Nal.1 NaCh and not other NAChs; 4) Based upon our QRT-PCR results, it does not appear that sodium-calcium exhanger genes, namely NCXl, NCX2 and NCX3, re involved in the NaCh mechanisms of ischemia brain injury, at least not at early time-points post-MCAo injury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA406069
Entities
People
- Frank C. Tortella
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine