Expression of neurotrophin and trk receptor genes in adult rats with fimbria transections: effect of intraventricular nerve growth factor and brain-derived neurotrophic factor administration.
The expression of the specific trk receptors for nerve growth factor and brain-derived neurotrophic factor (trkA and trkB) has been assayed by messenger RNA in situ hybridization in adult rats with partial fimbrial transections along with intraventricular treatment of nerve growth factor or brain-derived neurotrophic factor. In the forebrain, specific hybridization labeling for trkA messenger RNA showed an identical pattern to that of choline acetyltransferase messenger RNA, supporting the view that trkA expression is confined to the cholinergic population in the basal forebrain and the cholinergic interneurons in the striatum. After partial unilateral transections of the fimbria there was a progressive loss of choline acetyltransferase and trkA messenger RNA expression in the septal region ipsilateral to the lesion. Daily intraventricular administration of brain-derived neurotrophic factor or nerve growth factor partially prevented the lesion-induced decrease in the levels of both messengers, the latter being more effective than the former. Grain count analysis of individual cells was used to test whether the two factors upregulated choline acetyltransferase or trkA expression in individual cells surviving the lesion. Brain-derived neurotrophic factor treatment failed to induce any change in the levels of both messengers per neuron in the septal area. In contrast, daily intraventricular administration of nerve growth factor upregulated both choline acetyltransferase and trkA messenger RNA expression in individual neurons. This upregulation was evident on ipsilateral and contralateral sides, suggesting that nerve growth factor is able to upregulate these markers in intact and injured cholinergic cells in the basal forebrain. Similar to the situation in the septum, brain-derived neurotrophic factor did not upregulate choline acetyltransferase or trkA expression in the striatum. However, nerve growth factor administration strongly upregulated choline acetyltransferase messenger RNA expression by individual cholinergic neurons of the striatum. A medial to lateral gradient decrease in this upregulation was detected in the striatum ipsilateral to the side of administration, suggesting a limited diffusion of the nerve growth factor protein from the ventricle into brain parenchyma. In contrast to the strong effect on choline acetyltransferase expression, nerve growth factor treatment was ineffective in altering trkA messenger RNA in the striatum. The contrasting findings between septum and striatum suggest different regulatory mechanisms for trkA messenger RNA expression in the two cholinergic populations. Since nerve growth factor was found to upregulate the expression of its trkA receptor, we tested whether brain-derived neurotrophic factor administration had similar effects on the regulation of its trkB receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
Venero
J L
JL
Division of Neurogerontology, Ethel Percy Andrus Gerontology Center, University of Southern California, University Park, Los Angeles 90089-0191.
Knüsel
B
B
Beck
K D
KD
Hefti
F
F
D000818:Animals; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000293:injuries*; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D020917:Receptor, trkA; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012686:Septal Nuclei / Q000378:metabolism; D013377:Substantia Innominata / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D002795:Choline O-Acetyltransferase; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA