Increased production of the TrkB protein tyrosine kinase receptor after brain insults.
The protein-tyrosine kinases Trk, TrkB, and TrkC are signal-transducing receptors for a family of neurotrophic factors known as the neurotrophins. Here we show that seizures induced by hippocampal kindling lead to a rapid, transient increase of trkB mRNA and protein in the hippocampus. TrkB is a component of a high affinity receptor for brain-derived neurotrophic factor (BDNF). No change was detected in mRNAs for Trk or TrkC, components of the high affinity nerve growth factor or neurotrophin-3 receptors, respectively. trkB mRNA was also transiently increased in the dentate gyrus following cerebral ischemia and hypoglycemic coma; these treatments had no effect on trk and trkC mRNAs. The increase in trkB mRNA and protein showed the same time course and distribution as the increase in BDNF mRNA. These data suggest that BDNF and its receptor may play a local role within the hippocampus in kindling-associated neural plasticity and in neuronal protection following epileptic, ischemic, and hypoglycemic insults.
Merlio
J P
JP
Department of Medical Chemistry, Karolinska Institute, Stockholm, Sweden.
Ernfors
P
P
Kokaia
Z
Z
Middlemas
D S
DS
Bengzon
J
J
Kokaia
M
M
Smith
M L
ML
Siesjö
B K
BK
Hunter
T
T
Lindvall
O
O
D000818:Animals; D001483:Base Sequence; D001927:Brain Diseases / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor; D003128:Coma / Q000209:etiology / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007003:Hypoglycemia / Q000150:complications; D007696:Kindling, Neurologic; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020801:Receptor, Ciliary Neurotrophic Factor; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D012640:Seizures / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases; D020812:Receptor, trkC