PMID- 28386642
OWN - NLM
STAT- MEDLINE
DCOM- 20180306
LR  - 20181113
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 62
IP  - 1
DP  - 2017 May
TI  - Absence of Carboxypeptidase E/Neurotrophic Factor-Alpha1 in Knock-Out Mice Leads to 
      Dysfunction of BDNF-TRKB Signaling in Hippocampus.
PG  - 79-87
LID - 10.1007/s12031-017-0914-0 [doi]
AB  - Carboxypeptidase E (CPE), first discovered as a prohormone processing enzyme, has 
      also now been shown to be a secreted neurotrophic factor (neurotrophic factor-alpha1, 
      NF-alpha1) that acts extracellularly as a signaling molecule to mediate 
      neuroprotection, cortical stem cell differentiation, and antidepressive-like 
      behavior in mice. Since brain-derived neurotrophic factor (BDNF) has very similar 
      trophic functions, and its processing from pro-BDNF involves intracellular 
      sorting of pro-BDNF to the regulated secretory pathway by CPE acting as a sorting 
      receptor, we investigated whether the lack of CPE/NF-alpha1 would affect BDNF-TrkB 
      signaling in mice. Previous studies have shown that CPE/NF-alpha1 knock-out (KO) mice 
      exhibited severe neurodegeneration of the hippocampal CA3 region which raises the 
      question of why other neurotrophic factors such as BDNF could not compensate for 
      the deficiency of CPE. Here, we show that the expressions of pro-BDNF mRNA and 
      protein in hippocampus of CPE-KO mice were similar to WT mice, but mature BDNF 
      was  approximately 40% less in the CPE-KO mice, suggesting decreased intracellular processing 
      of pro-BDNF. Furthermore, TrkB receptor levels were similar in both genotypes, 
      but there was significantly decreased phosphorylation of TrkB receptor in the 
      CPE-KO mice. Electrophysiological studies showed lack of formation of long-term 
      potentiation in hippocampal slices of CPE-KO mice compared to WT mice, which was 
      not rescued by application of BDNF, indicating dysfunction of the BDNF-TrkB 
      signaling system. The CPE-KO mice showed normal postsynaptic AMPA response to 
      kainate application in hippocampal slices and dissociated neurons. Our findings 
      indicate that CPE/NF-alpha1 is essential for normal BDNF-TrkB signaling function in 
      mouse hippocampus.
FAU - Xiao, Lan
AU  - Xiao L
AD  - Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, 49, Convent 
      Drive, Bldg 49, Rm 6A-10, NICHD, NIH, Bethesda, MD, 20892, USA.
FAU - Chang, Su-Youne
AU  - Chang SY
AD  - Department of Neurologic Surgery and Physiology, Mayo Clinic, Rochester, MN, 
      55905, USA.
FAU - Xiong, Zhi-Gang
AU  - Xiong ZG
AD  - Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, 
      Atlanta, GA, 30310, USA.
FAU - Selveraj, Prabhuanand
AU  - Selveraj P
AD  - Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, 49, Convent 
      Drive, Bldg 49, Rm 6A-10, NICHD, NIH, Bethesda, MD, 20892, USA.
FAU - Peng Loh, Y
AU  - Peng Loh Y
AD  - Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, 49, Convent 
      Drive, Bldg 49, Rm 6A-10, NICHD, NIH, Bethesda, MD, 20892, USA. 
      lohp@mail.nih.gov.
LA  - eng
PT  - Journal Article
DEP - 20170406
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Receptors, AMPA)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.17.10 (Carboxypeptidase H)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism/pharmacology
MH  - CA3 Region, Hippocampal/cytology/*metabolism
MH  - Carboxypeptidase H/*genetics/metabolism
MH  - Cells, Cultured
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Kainic Acid/pharmacology
MH  - Long-Term Potentiation
MH  - Mice
MH  - Neurons/drug effects/metabolism/physiology
MH  - Receptor, trkB/*metabolism
MH  - Receptors, AMPA/agonists
MH  - *Signal Transduction
OTO - NOTNLM
OT  - Brain derived neurotrophic factor
OT  - Carboxypeptidase E
OT  - Long-term potentiation
OT  - Neurotrophic factor-alpha1
OT  - TrkB
EDAT- 2017/04/08 06:00
MHDA- 2018/03/07 06:00
CRDT- 2017/04/08 06:00
PHST- 2017/01/25 00:00 [received]
PHST- 2017/03/29 00:00 [accepted]
PHST- 2017/04/08 06:00 [pubmed]
PHST- 2018/03/07 06:00 [medline]
PHST- 2017/04/08 06:00 [entrez]
AID - 10.1007/s12031-017-0914-0 [pii]
AID - 10.1007/s12031-017-0914-0 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2017 May;62(1):79-87. doi: 10.1007/s12031-017-0914-0. Epub 2017 
      Apr 6.