PMID- 15262269
OWN - NLM
STAT- MEDLINE
DCOM- 20040924
LR  - 20131121
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 16
IP  - 3
DP  - 2004 Aug
TI  - Late onset loss of hippocampal 5-HT and NE is accompanied by increases in BDNF 
      protein expression in mice co-expressing mutant APP and PS1.
PG  - 572-80
AB  - Transgenic mice expressing both mutant amyloid precursor protein (APPswe) and 
      presenilin-1 (PS1DeltaE9) develop amyloid deposits as early as 4 months of age 
      and preliminary evidence suggests that this may be associated with degenerative 
      changes in serotonin axons innervating the dentate gyrus of the hippocampus. In 
      the present investigation, which focused on further delineating the effects of 
      amyloid deposition on hippocampal neurochemistry, decreases in serotonin 
      neurotransmitter levels (-25%) were discovered to be present at 18 months in 
      APP+/PS1+ mice, while norepinephrine was reduced in the hippocampus of 12- (-30%) 
      and 18-month-old (-45%) APP+/PS1+ double mutants. In addition, brain-derived 
      neurotrophic factor (BDNF) protein levels were investigated since changes in BDNF 
      are reported to occur in AD, and BDNF has been shown to have trophic effects on 
      serotonin and norepinephrine neurons. In doubly, but not singly mutant mice, 
      hippocampal BDNF levels were increased at 12 (+70%) and 18 months (+170%). 
      Furthermore, in a different model of serotonergic and noradrenergic degeneration, 
      BDNF protein levels were similarly increased in response to depletions in 
      hippocampal serotonin and norepinephrine caused by the chemical neurotoxin 
      1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP). These 
      findings show that early amyloid deposition in mice expressing mutant human APP 
      and PS-1 is associated with a progressive loss of serotonin and norepinephrine 
      neurotransmitter levels in the hippocampus later in life. Furthermore, BDNF 
      protein levels are increased in APP+/PS1+ and 2'-NH2-MPTP-treated mice, possibly 
      as a compensatory response to serotonergic and noradrenergic neurodegeneration in 
      a brain region important for learning and memory.
FAU - Szapacs, Matthew E
AU  - Szapacs ME
AD  - Department of Chemistry and the Huck Institute for Life Sciences, The 
      Pennsylvania State University, University Park, PA 16802-4615, USA.
FAU - Numis, Adam L
AU  - Numis AL
FAU - Andrews, Anne M
AU  - Andrews AM
LA  - eng
GR  - R03 MH067713-01/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
RN  - 108114-93-8 (1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine)
RN  - 333DO1RDJY (Serotonin)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*analogs & derivatives/pharmacology
MH  - Age Factors
MH  - Amyloid beta-Protein Precursor/*genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Corpus Striatum/metabolism
MH  - Dopamine/metabolism
MH  - Hippocampus/drug effects/*metabolism
MH  - Humans
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Transgenic
MH  - Norepinephrine/*metabolism
MH  - Presenilin-1
MH  - Serotonin/*metabolism
EDAT- 2004/07/21 05:00
MHDA- 2004/09/25 05:00
CRDT- 2004/07/21 05:00
PHST- 2003/09/10 00:00 [received]
PHST- 2004/02/11 00:00 [revised]
PHST- 2004/04/16 00:00 [accepted]
PHST- 2004/07/21 05:00 [pubmed]
PHST- 2004/09/25 05:00 [medline]
PHST- 2004/07/21 05:00 [entrez]
AID - S0969996104001020 [pii]
AID - 10.1016/j.nbd.2004.04.010 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2004 Aug;16(3):572-80. doi: 10.1016/j.nbd.2004.04.010.