Carboxypeptidase E knockout mice exhibit abnormal dendritic arborization and spine morphology in central nervous system neurons.
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.
Woronowicz
Alicja
A
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Cawley
Niamh X
NX
Chang
Su-Youne
SY
Koshimizu
Hisatsugu
H
Phillips
Andrè W
AW
Xiong
Zhi-Gang
ZG
Loh
Y Peng
YP
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000378:metabolism; D043423:Carboxypeptidase H / Q000235:genetics* / Q000378:metabolism; D048430:Cell Shape / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D003712:Dendrites / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016622:Silver Staining
D043423:Carboxypeptidase H