PMID- 9928439
OWN - NLM
STAT- MEDLINE
DCOM- 19990224
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 854
DP  - 1998 Nov 20
TI  - Age-associated memory impairment. Assessing the role of nitric oxide.
PG  - 307-17
AB  - Several neurotransmitter systems have been investigated to assess hypothesized 
      mechanisms underlying the decline in recent memory abilities in normal aging and 
      in Alzheimer's disease. Examining the performance of F344 rats in a 14-unit 
      T-maze (Stone maze), we have focused on the muscarinic cholinergic (mACh) and the 
      N-methyl-D-aspartate (NMDA) glutamate (Glu) systems and their interactions. Maze 
      learning is impaired by antagonists to mACh or NMDA receptors. We have also shown 
      that stimulation of mACh receptors can overcome a maze learning deficit induced 
      by NMDA blockade, and stimulation of the NMDA receptor can overcome a similar 
      blockade of mACh receptors. No consistent evidence in rats has been produced from 
      our laboratory to reveal significant age-related declines in mACh or NMDA 
      receptor binding in the hippocampus (HC), a brain region that is greatly involved 
      in processing of recent memory. Thus, we have directed attention to the 
      possibility of a common signal transduction pathway, the nitric oxide (NO) 
      system. Activated by calcium influx through the NMDA receptor, NO is hypothesized 
      to be a retrograde messenger that enhances presynaptic Glu release. Maze learning 
      can be impaired by inhibiting the synthetic enzyme for NO, nitric oxide synthase 
      (NOS), or enhanced by stimulating NO release. However, we have found no 
      age-related loss of NOS-containing HC neurons or fibers in rats. Additionally, 
      other laboratories have reported no evidence of an age-related loss of HC NOS 
      activity. In a microdialysis study we have found preliminary evidence of reduced 
      NO production following NMDA stimulation. We are currently working to identify 
      the parameters of this phenomenon as well as testing various strategies for 
      safely stimulating the NO system to improve memory function in aged rats.
FAU - Meyer, R C
AU  - Meyer RC
AD  - Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of 
      Health, Baltimore, Maryland 21224, USA.
FAU - Spangler, E L
AU  - Spangler EL
FAU - Kametani, H
AU  - Kametani H
FAU - Ingram, D K
AU  - Ingram DK
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Aging/*physiology/*psychology
MH  - Animals
MH  - Hippocampus/growth & development/*physiology
MH  - *Maze Learning
MH  - Memory/*physiology
MH  - *Memory Disorders
MH  - Models, Neurological
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Synthase/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, Muscarinic/physiology
MH  - Receptors, N-Methyl-D-Aspartate/physiology
MH  - Signal Transduction
RF  - 62
EDAT- 1999/02/03 00:00
MHDA- 1999/02/03 00:01
CRDT- 1999/02/03 00:00
PHST- 1999/02/03 00:00 [pubmed]
PHST- 1999/02/03 00:01 [medline]
PHST- 1999/02/03 00:00 [entrez]
AID - 10.1111/j.1749-6632.1998.tb09911.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 1998 Nov 20;854:307-17. doi: 
      10.1111/j.1749-6632.1998.tb09911.x.