Mutation of the trkB gene encoding the high-affinity receptor for brain-derived neurotrophic factor in stroke-prone spontaneously hypertensive rats.

Abstract

Brain-derived neurotrophic factor and its receptor, trkB, are thought to play a crucial role for protection against neuronal death induced by brain ischemia, such as in stroke. In the present study we found a missense mutation in the trkB gene from all of the five substrains of stroke-prone spontaneously hypertensive rats (SHRSP) that were examined. This mutation was not found in six out of seven hypertensive but stroke-resistant ancestral strains (SHR) of SHRSP, nor in any of seven strains of normotensive, non-stroke-prone strains. Hippocampal neurons, which are particularly vulnerable to damage in stroke, were shown to be more susceptible to ischemic damage in SHRSP than in either SHR or normotensive, stroke-resistant controls. The association of a mutated trkB gene with the stroke-prone genotype found in this study suggests that the trkB gene merits further study as a promising candidate gene for stroke.

• Authors: H Kageyama, K Nemoto, F Nemoto, M Sekimoto, Y Nara, T Nabika, Y Iwayama, K Fukamachi, I Tomita, E Senba, C J Forehand, E D Hendley, T Ueyama
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 229 Issue 3 Pg. 713-8 (Dec 24 1996) ISSN: 0006-291X [Print] United States
• PMID: 8954962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptor, Ciliary Neurotrophic Factor
• Receptors, Nerve Growth Factor

Topics

• Animals
• Brain Chemistry
• Cerebrovascular Disorders (genetics)
• Mutation
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptor, Ciliary Neurotrophic Factor
• Receptors, Nerve Growth Factor (genetics)