PMID- 9191090
OWN - NLM
STAT- MEDLINE
DCOM- 19970805
LR  - 20190826
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 46
IP  - 1-2
DP  - 1997 Jun
TI  - Pharmacological modulation of Alzheimer's beta-amyloid precursor protein levels 
      in the CSF of rats with forebrain cholinergic system lesions.
PG  - 161-8
AB  - Abnormal deposition and accumulation of Alzheimer's amyloid beta-protein (A beta) 
      and degeneration of forebrain cholinergic neurons are among the principal 
      features of Alzheimer's disease. Studies in rat model systems have shown that 
      forebrain cholinergic deficits are accompanied by induction of cortical 
      beta-amyloid precursor protein (beta-APP) mRNAs and increased levels of secreted 
      beta-APP in the CSF. The studies reported here determined whether the CSF levels 
      of secreted beta-APP could be altered pharmacologically. In different 
      experiments, rats with lesions of the forebrain cholinergic system received 
      injections of vehicle, a muscarinic receptor antagonist scopolamine, or one of 
      two cholinesterase inhibitors - diisopropyl phosphorofluoridate (DFP) or 
      phenserine. Scopolamine was administered to determine whether the levels of 
      beta-APP in the CSF could be increased by anticholinergic agents. The 
      cholinesterase inhibitors were administered to determine whether the forebrain 
      cholinergic system lesion-induced increases in CSF beta-APP could be reduced by 
      cholinergic augmentation. Scopolamine administration led to a significant 
      increase in the CSF levels of secreted beta-APP in sham-lesioned rats. 
      Phenserine, a novel, reversible acetyl-selective cholinesterase inhibitor, 
      significantly decreased the levels of secreted beta-APP in the CSF of forebrain 
      cholinergic system-lesioned rats whereas DFP, a relatively non-specific 
      cholinesterase inhibitor, failed to affect CSF levels of secreted beta-APP. These 
      results suggest that the levels of secreted beta-APP in the CSF can be 
      pharmacologically modulated but that this modulation is dependent upon the status 
      of the forebrain cholinergic system and the pharmacological properties of the 
      drugs used to influence it.
FAU - Haroutunian, V
AU  - Haroutunian V
AD  - Department of Psychiatry, Mount Sinai School of Medicine and Bronx VA Medical 
      Center, NY 10468, USA.
FAU - Greig, N
AU  - Greig N
FAU - Pei, X F
AU  - Pei XF
FAU - Utsuki, T
AU  - Utsuki T
FAU - Gluck, R
AU  - Gluck R
FAU - Acevedo, L D
AU  - Acevedo LD
FAU - Davis, K L
AU  - Davis KL
FAU - Wallace, W C
AU  - Wallace WC
LA  - eng
GR  - R01-AG10138/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Muscarinic Antagonists)
RN  - 12UHW9R67N (Isoflurophate)
RN  - 9U1VM840SP (Physostigmine)
RN  - DL48G20X8X (Scopolamine)
RN  - SUE285UG3S (phenserine)
SB  - IM
MH  - Alzheimer Disease/metabolism
MH  - Amyloid beta-Protein Precursor/*cerebrospinal fluid/*drug effects
MH  - Animals
MH  - Cholinesterase Inhibitors/*pharmacology
MH  - Isoflurophate/pharmacology
MH  - Male
MH  - Muscarinic Antagonists/pharmacology
MH  - Physostigmine/analogs & derivatives/pharmacology
MH  - Prosencephalon/*drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Scopolamine/pharmacology
EDAT- 1997/06/01 00:00
MHDA- 1997/06/01 00:01
CRDT- 1997/06/01 00:00
PHST- 1997/06/01 00:00 [pubmed]
PHST- 1997/06/01 00:01 [medline]
PHST- 1997/06/01 00:00 [entrez]
AID - S0169-328X(96)00297-5 [pii]
AID - 10.1016/s0169-328x(96)00297-5 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 1997 Jun;46(1-2):161-8. doi: 
      10.1016/s0169-328x(96)00297-5.