Carboxypeptidase E knockout mice exhibit abnormal dendritic arborization and spine morphology in central nervous system neurons

J Neurosci Res. 2010 Jan;88(1):64-72. doi: 10.1002/jnr.22174.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / cytology*
  • CA1 Region, Hippocampal / metabolism
  • Carboxypeptidase H / genetics*
  • Carboxypeptidase H / metabolism
  • Cell Shape / genetics
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / metabolism
  • Dendrites / genetics*
  • Dendrites / metabolism
  • Mice
  • Mice, Knockout
  • Silver Staining

Substances

  • Carboxypeptidase H