Myelination in the hippocampus during development and following lesion |
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| Authors: | S?Meier A?U?Br?uer B?Heimrich R?Nitsch Email author" target="_blank">N?E?SavaskanEmail author |
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| Institution: | (1) Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité University Medical School Berlin, Philippstr. 12, 10115 Berlin, Germany;(2) Institute of Anatomy and Cell Biology I, Albert-Friedrichs University of Freiburg, Freiburg, Germany;(3) Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 OX Amsterdam, The Netherlands |
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| Abstract: | Myelin is crucial for the stabilization of axonal projections in the developing and adult mammalian brain. However, myelin
components also act as a non-permissive and repellent substrate for outgrowing axons. Therefore, one major factor which accounts
for the lack of axonal regeneration in the mature brain is myelin. Here we report on the appearance of mature, fully myelinated
axons during hippocampal development and following entorhinal lesion with the myelin-specific marker Black Gold. Although
entorhinal axons enter the hippocampal formation at embryonic day 17, light and ultrastructural analysis revealed that mature
myelinated fibers in the hippocampus occur in the second postnatal week. During postnatal development, increasing numbers
of myelinated fibers appear and the distribution of myelinated fibers at postnatal day 25 was similar to that found in the
adult. After entorhinal cortex lesion, a specific anterograde denervation in the hippocampus takes place, accompanied by a
long-lasting loss of myelin. Quantitative analysis of myelin and myelin breakdown products at different time points after
lesion revealed a temporally close correlation to the degeneration and reorganization pha-ses in the hippocampus. In contrast,
electroconvulsive seizures resulted in brief demyelination and a faster recovery time course. In conclusion, we could show
that the appearance of mature axons in the hippocampus is temporally regulated during development. In the adult hippocampus,
demyelination was found after anterograde degeneration and also following seizures, suggesting that independent types of insult
lead to demyelination. Reappearing mature axons were found in the hippocampus following axonal sprouting. Therefore, our quantitative
analysis of mature axons and myelination effectively reflects the readjusted axonal density and possible electrophysiological
balance following lesion.
Received 22 December 2003; received after revision 11 February 2004; accepted 17 February 2004 |
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| Keywords: | Myelin-associated axon growth inhibition Nogo gene seizure axonal guidance myelo-architecture myelin basic protein sprouting demyelination |
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