PMID- 11191712
OWN - NLM
STAT- MEDLINE
DCOM- 20010308
LR  - 20190910
IS  - 0278-5846 (Print)
IS  - 0278-5846 (Linking)
VI  - 24
IP  - 5
DP  - 2000 Jul
TI  - Initiation and propagation of molecular cascades in human brain aging: insight 
      from the canine model to promote successful aging.
PG  - 777-86
AB  - 1. Normal aging is thought to proceed through two stages: initiation and 
      propagation. Each of these phases is associated with different neuroanatomical 
      events, vulnerabilities to injury and responsiveness to interventions. 2. The 
      role of beta-amyloid (Abeta) in neuron dysfunction in the initiation stage may be 
      mediated through alterations in signal transduction pathways involving cyclic AMP 
      response element binding protein (CREB). CREB phosphorylation is associated with 
      the expression of brain derived neurotrophic factor (BDNF), which promotes neuron 
      health and survival. In primary neuronal cultures, Abeta decreases the 
      phosphorylation of CREB, which results in up to a 31% decrease in BDNF levels. 3. 
      In vivo studies also support a role for Abeta in neuron dysfunction since soluble 
      Abeta levels correlate with the loss of synapses in brains of non-demented humans 
      with high pathology. 4. The authors hypothesize that interventions during the 
      initiation stage, when neuron dysfunction, but not overt pathology, is present, 
      have the most promise to promote successful aging. The dog can serve as a useful 
      model for interventions during the initiation stage since dogs develop 
      neuropathology that closely resembles that observed in high pathology human 
      brains.
FAU - Head, E
AU  - Head E
AD  - Institute for Brain Aging & Dementia, University of California-Irvine, 
      92697-4540, USA. ehead@uci.edu
FAU - Thornton, P L
AU  - Thornton PL
FAU - Tong, L
AU  - Tong L
FAU - Cotman, C W
AU  - Cotman CW
LA  - eng
GR  - AG12694/AG/NIA NIH HHS/United States
GR  - AG13411/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Amyloid beta-Peptides)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Aging/*pathology
MH  - Amyloid beta-Peptides/metabolism/*pharmacology
MH  - Animals
MH  - Brain/*pathology
MH  - Cyclic AMP/metabolism
MH  - Disease Models, Animal
MH  - Dogs
MH  - Humans
MH  - Neurons/pathology
MH  - Signal Transduction
RF  - 39
EDAT- 2001/02/24 12:00
MHDA- 2001/03/10 10:01
CRDT- 2001/02/24 12:00
PHST- 2001/02/24 12:00 [pubmed]
PHST- 2001/03/10 10:01 [medline]
PHST- 2001/02/24 12:00 [entrez]
AID - S0278584600001056 [pii]
AID - 10.1016/s0278-5846(00)00105-6 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2000 Jul;24(5):777-86. doi: 
      10.1016/s0278-5846(00)00105-6.