PMID- 11805198
DA - 20020125
IS - 0022-3565
VI - 300
IP - 2
DP - 2002 Feb
TI - Pharmacological protection of synaptic function, spatial learning, and memory from transient hypoxia in rats.
PG - 408-16 AB - Hypoxia significantly reduced cholinergic theta activity in rat CA1 field and intracellular theta in the CA1 pyramidal cells, recorded in hippocampal slices. The hypoxic responses of the hippocampal CA1 pyramidal cells to a brief hypoxia consisted of a short period of "synaptic arrest", observed as an elimination of excitatory postsynaptic current under voltage clamp and recovered immediately as oxygenation was reinitiated. The hypoxic synaptic arrest was not associated with reduced postsynaptic responses of the pyramidal cells to externally applied L-glutamate, suggesting that the synaptic arrest might result from a presynaptic mechanism. The hypoxic synaptic arrest was abolished in the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific adenosine A(1) receptor antagonist. Blocking adenosine A(1) receptors also eliminated effects of hypoxia on the hippocampal CA1 field theta activity and intracellular theta of the CA1 pyramidal cells. In behaving rats, brief hypoxia impaired their water maze performance in both the escape latency and probe tests. The impairment was prevented by intralateral cerebroventricular injections of DPCPX. These results suggest that hypoxia releases adenosine and produces an inhibition of synaptic transmission and intracellular signal cascade(s) involved in generation/maintenance of hippocampal CA1 theta activity. This protection of synaptic efficacy and spatial learning through adenosine A(1) receptor antagonism may represent an effective therapeutic strategy to eliminate functional interruption due to transient hypoxic episodes and/or chronic hypoxia secondary to compromise of respiratory function.
AD - Blanchette Rockefeller Neurosciences Institute, Rockville, Maryland; and
Laboratory of Adaptive Systems, National Institute of Neurological
Disorders and Stroke/National Institutes of Health, Bethesda, Maryland.
FAU - Sun, Miao-Kun
AU - Sun MK
FAU - Xu, Hui
AU - Xu H
FAU - Alkon, Daniel L
AU - Alkon DL
LA - eng
PT - Journal Article
CY - United States
TA - J Pharmacol Exp Ther
JID - 0376362
SB - IM
EDAT- 2002/01/24 10:00
MHDA- 2002/01/24 10:00
URLF- http://www.jpet.org/cgi/content/full/300/2/408
URLS- http://www.jpet.org/cgi/content/abstract/300/2/408
PST - ppublish
SO - J Pharmacol Exp Ther 2002 Feb;300(2):408-16.