CORRELATED LONG-TERM INCREASE OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND TRK-B PROTEINS IN ENLARGED GRANULE CELLS OF MOUSE HIPPOCAMPUS AFTER KAINIC ACID INJECTION

Our previous studies have shown that a single injection of kainic acid into the dorsal hippocampus of adult mice resulted in hypertrophy of the dentate gyrus granule cells. This hypertrophy was correlated with a long-lasting increase of brain-derived neurotrophic factor messenger RNA, and prevented by anti-sense brain-derived neurotrophic factor ol igonucleotide treatment. These results suggest that an increase of bra in-derived neurotrophic factor messenger RNA may be a major trigger of granule cells enlargement. However, the level of messenger RNA of Trk B, the high-affinity receptor of brain-derived neurotrophic factor, w as not increased significantly, raising the question of whether increa sed brain-derived neurotrophic factor messenger RNA level leads actual ly to an increased protein production. The objective of the present st udy was to examine this; changes in contents of brain-derived neurotro phic factor and TrkB protein were monitored by immunohistochemistry du ring kainic acid-induced hypertrophy. Results show that immunoreactivi ties of brain-derived neurotrophic factor and Trk B were present in en larged granule cells. These immunoreactivities increased from two to 1 6 weeks after kainic acid injection and were maintained up to 12 month s. Simultaneous increases of brain-derived neurotrophic Factor messeng er RNA and protein, and of TrkB protein were coupled tightly to the ch ronology of granule cell enlargement, suggesting that the action of br ain-derived neurotrophic factor in the induction and maintenance of ka inic acid-induced granule cells enlargement is likely to be mediated b y TrkB. The discrepancy between the previously described lack of incre ase of TrkB messenger RNA and the herein observed increase of the prot ein further reveals the existence of translational regulations of the receptor messenger RNA. (C) 1998 IBRO. Published by Elsevier Science L td.