MUTATION OF THE TRKB GENE ENCODING THE HIGH-AFFINITY RECEPTOR FOR BRAIN-DERIVED NEUROTROPHIC FACTOR IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

Brain-derived neurotrophic factor and its receptor, trkB, are thought to play a crucial role for protection against neuronal death induced b y brain ischemia, such as in stroke. In the present study we found a m issense mutation in the trkB gene from all of the five substrains of s troke-prone spontaneously hypertensive rats (SHRSP) that were examined . This mutation was not found in six out of seven hypertensive but str oke-resistant ancestral strains (SHR) of SHRSP. nor in any of seven st rains of normotensive, non-stroke-prone strains. Hippocampal neurons, which are particularly vulnerable to damage in stroke, were shown to b e more susceptible to ischemic damage in SHRSP than in either SHR or n ormotensive stroke-resistant controls. The association of a mutated tr kB gene with the stroke-prone genotype found in this study suggests th at the trkB gene merits further study as a promising candidate gene fo r stroke. (C) 1996 Academic Press