PMID- 17015468
OWN - NLM
STAT- MEDLINE
DCOM- 20061226
LR  - 20220129
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 26
IP  - 23
DP  - 2006 Dec
TI  - Ca2+/calmodulin kinase kinase alpha is dispensable for brain development but is 
      required for distinct memories in male, though not in female, mice.
PG  - 9094-104
AB  - In neurons, the Ca(2+)/calmodulin (CaM) kinase cascade transduces Ca(2+) 
      signaling into gene transcription. The CaM kinase cascade is known to be 
      important for brain development as well as memory formation in adult brain, 
      although the functions of some cascade members remain unknown. Here we have 
      generated null and hypomorphic mutants to study the physiological role of CaM 
      kinase kinase alpha (CaMKKalpha), which phosphorylates and activates both CaM 
      kinase I (CaMKI) and CaMKIV, the output kinases of the cascade. We show that 
      CaMKKalpha is dispensable for brain development and long-term potentiation in 
      adult hippocampal CA1 synapses. We find that CaMKKalpha is required for 
      hippocampus-dependent contextual fear memory, but not spatial memory, formation. 
      Surprisingly, CaMKKalpha is important for contextual fear memory formation in 
      males but not in females. We show that in male mice, contextual fear conditioning 
      induces up-regulation of hippocampal mRNA expression of brain-derived 
      neurotrophic factor (BDNF) in a way that requires CaMKKalpha, while in female 
      mice, contextual fear conditioning induces down-regulation of hippocampal BDNF 
      mRNA expression that does not require CaMKKalpha. Additionally, we demonstrate 
      sex-independent up-regulation in hippocampal nerve growth factor-inducible gene B 
      mRNA expression that does not require CaMKKalpha. Thus, we show that CaMKKalpha 
      has a specific complex role in memory formation in males.
FAU - Mizuno, Keiko
AU  - Mizuno K
AD  - Institute of Psychiatry, King's College London, London SE5 8AF, United Kingdom.
FAU - Ris, Laurence
AU  - Ris L
FAU - Sanchez-Capelo, Amelia
AU  - Sanchez-Capelo A
FAU - Godaux, Emile
AU  - Godaux E
FAU - Giese, K Peter
AU  - Giese KP
LA  - eng
GR  - G0400983/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061002
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
RN  - EC 2.7.11.17 (Camkk1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Brain/*embryology/enzymology
MH  - Brain-Derived Neurotrophic Factor/physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinase Kinase
MH  - Conditioning, Psychological/physiology
MH  - Fear
MH  - Female
MH  - Hippocampus/physiology
MH  - Male
MH  - Memory/*physiology
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Protein Serine-Threonine Kinases/deficiency/genetics/*physiology
MH  - RNA, Messenger/metabolism
MH  - Sex Factors
MH  - Up-Regulation
PMC - PMC1636825
EDAT- 2006/10/04 09:00
MHDA- 2006/12/27 09:00
PMCR- 2007/04/01
CRDT- 2006/10/04 09:00
PHST- 2006/10/04 09:00 [pubmed]
PHST- 2006/12/27 09:00 [medline]
PHST- 2006/10/04 09:00 [entrez]
PHST- 2007/04/01 00:00 [pmc-release]
AID - MCB.01221-06 [pii]
AID - 1221-06 [pii]
AID - 10.1128/MCB.01221-06 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2006 Dec;26(23):9094-104. doi: 10.1128/MCB.01221-06. Epub 2006 Oct 
      2.