PMID- 22491352
OWN - NLM
STAT- MEDLINE
DCOM- 20121113
LR  - 20211021
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 37
IP  - 8
DP  - 2012 Jul
TI  - Reduced tissue levels of noradrenaline are associated with behavioral phenotypes 
      of the TgCRND8 mouse model of Alzheimer's disease.
PG  - 1934-44
LID - 10.1038/npp.2012.40 [doi]
AB  - Noradrenergic cell loss is well documented in Alzheimer's disease (AD). We have 
      measured the tissue levels of catecholamines in an amyloid precursor 
      protein-transgenic 'TgCRND8' mouse model of AD and found reductions in 
      noradrenaline (NA) within hippocampus, temporoparietal and frontal cortices, and 
      cerebellum. An age-related increase in cortical NA levels was observed in non-Tg 
      controls, but not in TgCRND8 mice. In contrast, NA levels declined with aging in 
      the TgCRND8 hippocampus. Dopamine levels were unaffected. Reductions in the 
      tissue content of NA were found to coincide with altered expression of 
      brain-derived neurotrophic factor (BDNF) mRNA and to precede the onset of object 
      memory impairment and behavioral despair. To test whether these phenotypes might 
      be associated with diminished NA, we treated mice with dexefaroxan, an antagonist 
      of presynaptic inhibitory alpha(2)-adrenoceptors on noradrenergic and cholinergic 
      terminals. Mice 12 weeks of age were infused systemically for 28 days with 
      dexefaroxan or rivastigmine, a cholinesterase inhibitor. Both dexefaroxan and 
      rivastigmine improved TgCRND8 behavioral phenotypes and increased BDNF mRNA 
      expression without affecting amyloid-beta peptide levels. Our results highlight the 
      importance of noradrenergic depletion in AD-like phenotypes of TgCRND8 mice.
FAU - Francis, Beverly M
AU  - Francis BM
AD  - Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 
      Toronto, ON, Canada.
FAU - Yang, Jimao
AU  - Yang J
FAU - Hajderi, Enid
AU  - Hajderi E
FAU - Brown, Mary E
AU  - Brown ME
FAU - Michalski, Bernadeta
AU  - Michalski B
FAU - McLaurin, Joanne
AU  - McLaurin J
FAU - Fahnestock, Margaret
AU  - Fahnestock M
FAU - Mount, Howard T J
AU  - Mount HT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120411
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Adrenergic alpha-2 Receptor Antagonists)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Benzopyrans)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Catecholamines)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Phenylcarbamates)
RN  - F751MO69EV (dexefaroxan)
RN  - PKI06M3IW0 (Rivastigmine)
RN  - TG537D343B (Desipramine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Adrenergic alpha-2 Receptor Antagonists/pharmacology
MH  - Aging/genetics/metabolism/psychology
MH  - Alzheimer Disease/genetics/*metabolism/*psychology
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/*genetics
MH  - Animals
MH  - Benzopyrans/pharmacology
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/biosynthesis
MH  - Catecholamines/*metabolism
MH  - Cholinesterase Inhibitors/pharmacology
MH  - Desipramine/pharmacology
MH  - Disease Models, Animal
MH  - Imidazoles/pharmacology
MH  - Immobility Response, Tonic/drug effects/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Phenylcarbamates/pharmacology
MH  - Recognition, Psychology/*drug effects
MH  - Rivastigmine
PMC - PMC3376325
EDAT- 2012/04/12 06:00
MHDA- 2012/11/14 06:00
PMCR- 2013/07/01
CRDT- 2012/04/12 06:00
PHST- 2012/04/12 06:00 [entrez]
PHST- 2012/04/12 06:00 [pubmed]
PHST- 2012/11/14 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - npp201240 [pii]
AID - 10.1038/npp.2012.40 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2012 Jul;37(8):1934-44. doi: 10.1038/npp.2012.40. Epub 
      2012 Apr 11.