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Regulation of Trophic Factor Expression by Innervating Target Regions in Intraocular Double Transplants
L Willis1, E M Quintero1, M Nelson1
1Department of Physiology and Neuroscience and the Center on Aging, Medical University of South Carolina, Charleston, SC 29425.
Abstract:
Trophic factors have been found to play a significant role both in long-term survival processes and in more rapid and dynamic processes in the brain and spinal cord. However, little is known regarding the regulation of expression of growth factors, and how these proteins interact on a cell-to-cell basis. We have studied protein levels of one growth factor known to affect the noradrenergic innervation of the hippocampal formation, namely brain-derived neurotrophic factor (BDNF). The purpose of the present study was to determine if appropriate innervation or contact between the LC noradrenergic neurons and their target, the hippocampus, affects expression of this growth factor in either brain region. Fetal brain stem tissue, containing the LC, and hippocampal formation were dissected from embryonic day 17 rat fetuses and transplanted together or alone into the anterior chamber of the eye of adult Fisher 344 rats. The tissue was grown together for 6 weeks, after which the animals were sacrificed and ELISAs for BDNF were undertaken. Transplantation to the anterior chamber of the eye increased the expression of BDNF in the hippocampal but not the brain stem tissue, compared with levels observed in fetal and adult rats in vivo. In addition, double grafting with hippocampal tissue more than tripled BDNF levels in brain stem grafts and doubled BDNF levels in the hippocampal portion of double grafts compared with hippocampal single grafts. Triple grafts containing basal forebrain, hippocampus, and brain stem LC tissue increased brain stem and hippocampal BDNF levels even further. Colchicine treatment of LC-hippocampal double grafts gave rise to a significant decrease in hippocampal BDNF levels to levels seen in single hippocampal grafts, while only a partial reduction of BDNF levels was seen in the brain stem portion of the same double grafts treated with colchicine. The findings suggest that an appropriate hippocampal innervation or contact with its target tissues is essential for regulation of BDNF expression in the brain stem, and that retrograde transport of BDNF can occur between double grafted fetal tissues in oculo.
Insights
Brain-derived neurotrophic factor (BDNF) expression in the hippocampus and brain stem is regulated by neural connections. Contact between these tissues in vivo influences BDNF levels, suggesting retrograde transport mechanisms.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Trophic factors are crucial for neural survival and function.
- Regulation of growth factor expression and cell-cell interactions in the nervous system are not well understood.
- Brain-derived neurotrophic factor (BDNF) influences noradrenergic innervation of the hippocampus.
Purpose of the Study:
- To investigate if neural connections between locus coeruleus (LC) noradrenergic neurons and the hippocampus affect BDNF expression.
- To determine the role of innervation and target tissue contact in regulating BDNF levels.
Main Methods:
- Fetal rat brain stem (LC) and hippocampal tissues were co-transplanted or transplanted individually into the anterior chamber of the eye.
- Tissues were grown for 6 weeks.
- BDNF protein levels were quantified using ELISAs.
- Colchicine treatment was used to assess axonal transport.
Main Results:
- Ocular transplantation increased hippocampal BDNF levels compared to in vivo controls.
- Co-grafting (hippocampus and brain stem) significantly elevated BDNF levels in both tissues compared to single grafts.
- Triple grafts further increased BDNF levels.
- Colchicine treatment reduced hippocampal BDNF but only partially reduced brain stem BDNF, suggesting retrograde transport.
Conclusions:
- Appropriate hippocampal innervation or target tissue contact is essential for regulating BDNF expression in the brain stem.
- Retrograde transport of BDNF occurs between connected fetal tissues grafted in the eye.
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