PMID- 24081304
OWN - NLM
STAT- MEDLINE
DCOM- 20140910
LR  - 20211021
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 39
IP  - 3
DP  - 2014 Feb
TI  - STAT1 negatively regulates spatial memory formation and mediates the 
      memory-impairing effect of Abeta.
PG  - 746-58
LID - 10.1038/npp.2013.263 [doi]
AB  - Signal transducer and activator of transcription-1 (STAT1) has an important role 
      in inflammation and the innate immune response, but its role in the central 
      nervous system is less well understood. Here, we examined the role of STAT1 in 
      spatial learning and memory, and assessed the involvement of STAT1 in mediating 
      the memory-impairing effect of amyloid-beta (Abeta). We found that water maze 
      training downregulated STAT1 expression in the rat hippocampal CA1 area, and 
      spatial learning and memory function was enhanced in Stat1-knockout mice. 
      Conversely, overexpression of STAT1 impaired water maze performance. STAT1 
      strongly upregulated the expression of the extracellular matrix protein laminin 
      beta1 (LB1), which also impaired water maze performance in rats. Furthermore, Abeta 
      impaired spatial learning and memory in association with a dose-dependent 
      increase in STAT1 and LB1 expression, but knockdown of STAT1 and LB1 both 
      reversed this effect of Abeta. This Abeta-induced increase in STAT1 and LB1 expression 
      was also associated with a decrease in the expression of the N-methyl-D-aspartate 
      receptor (NMDAR) subunits, NR1, and NR2B. Overexpression of NR1 or NR2B or 
      exogenous application of NMDA reversed Abeta-induced learning and memory deficits as 
      well as Abeta-induced STAT1 and LB1 expression. Our results demonstrate that STAT1 
      negatively regulates spatial learning and memory through transcriptional 
      regulation of LB1 expression. We also identified a novel mechanism for Abeta 
      pathogenesis through STAT1 induction. Notably, impairment of spatial learning and 
      memory by this STAT1-mediated mechanism is independent of cAMP responsive 
      element-binding protein signaling.
FAU - Hsu, Wei-Lun
AU  - Hsu WL
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
FAU - Ma, Yun-Li
AU  - Ma YL
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
FAU - Hsieh, Ding-You
AU  - Hsieh DY
AD  - 1] Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan [2] 
      Institute of Neuroscience, National Cheng-chi University, Taipei, Taiwan.
FAU - Liu, Yen-Chen
AU  - Liu YC
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
FAU - Lee, Eminy Hy
AU  - Lee EH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130930
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Lamb1 protein, mouse)
RN  - 0 (Laminin)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
SB  - IM
MH  - Amyloid beta-Peptides/*pharmacology
MH  - Animals
MH  - CREB-Binding Protein/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/*drug effects/genetics
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - Laminin/metabolism
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Memory Disorders/*chemically induced/genetics/*metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - RNA, Small Interfering/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - STAT1 Transcription Factor/*deficiency/genetics
MH  - Space Perception/*drug effects/physiology
PMC - PMC3895253
EDAT- 2013/10/02 06:00
MHDA- 2014/09/11 06:00
PMCR- 2014/02/01
CRDT- 2013/10/02 06:00
PHST- 2013/04/30 00:00 [received]
PHST- 2013/08/29 00:00 [revised]
PHST- 2013/09/16 00:00 [accepted]
PHST- 2013/10/02 06:00 [entrez]
PHST- 2013/10/02 06:00 [pubmed]
PHST- 2014/09/11 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - npp2013263 [pii]
AID - 10.1038/npp.2013.263 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2014 Feb;39(3):746-58. doi: 10.1038/npp.2013.263. Epub 
      2013 Sep 30.