期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 88, 期 1, 页码 64-72出版社
WILEY
DOI: 10.1002/jnr.22174
关键词
carboxypeptidase E; dendritic pruning; hippocampus; BDNF
资金
- NIH [RO1NS049470]
- Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS049470] Funding Source: NIH RePORTER
Carboxypeptidase E (CPE) is involved in maturation of neuropeptides and sorting of brain-derived neurotrophic factor (BDNF) to the regulated pathway for activity-dependent secretion from CNS neurons. CPE knockout (CPE-KO) mice have many neurological deficits, including deficits in learning and memory. Here, we analyzed the dendritic arborization and spine morphology of CPE-KO mice to determine a possible correlation of defects in such structures with the neurological deficits observed in these animals. Analysis of pyramidal neurons in layer V of cerebral cortex and in hippocampal CA1 region in 14-week-old CPE-KO mice showed more dendritic complexity compared with wild type (WT) mice. There were more dendritic intersections and more branch points in CPE-KO vs. WT neurons. Comparison of pyramidal cortical neurons in 6- vs. 14-week-old WT mice showed a decrease in dendritic arborization, reflecting the occurrence of normal dendritic pruning. However, this did not occur in CPE-KO neurons. Furthermore, analysis of spine morphology demonstrated a significant increase in the number of D-type spines regarded as nonfunctional in the cortical neurons of CPE-KO animals. Our findings suggest that CPE is an important, novel player in mediating appropriate dendritic patterning and spine formation in CNS neurons. (C) 2009 Wiley-Liss, Inc.
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