Izumi Y, Katsuki H, Benz A M, Zorumski C F
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Cereb Blood Flow Metab. 1998 Jan;18(1):97-108. doi: 10.1097/00004647-199801000-00010.
The acute and delayed effects of anoxia on synaptic transmission and long-term potentiation (LTP) were examined in the CA1 region of rat hippocampal slices. Oxygen deprivation for 20 minutes completely but reversibly depressed excitatory postsynaptic potentials mediated by both N-methyl-D-aspartate receptors (NMDAR) and non-NMDAR. Although LTP was reliably produced by a single tetanus delivered 30 minutes after reoxygenation, LTP could not be induced when a tetanus was delivered 70 to 100 minutes after reoxygenation. A tetanus delivered 100 minutes after reoxygenation produced lasting synaptic enhancement when 100 mumol/L D,L-amino-phosphonovaleric acid (APV), a competitive NMDAR antagonist, was administered during the period of oxygen deprivation. The delayed effects of oxygen deprivation were not blocked when APV was administered after oxygen deprivation. Similarly, the delayed effects on LTP induction were overcome by inhibitors of nitric oxide synthase when the nitric oxide synthase inhibitors were administered during anoxia, but not when administered after oxygen deprivation. These results suggest that untimely activation of NMDAR and nitric oxide release during anoxia produce delayed inhibition of LTP induction and may be involved in the memory defects that occur subsequent to cerebral hypoxia.
在大鼠海马切片的CA1区检测了缺氧对突触传递和长时程增强（LTP）的急性和延迟效应。缺氧20分钟可完全但可逆地抑制由N-甲基-D-天冬氨酸受体（NMDAR）和非NMDAR介导的兴奋性突触后电位。尽管复氧30分钟后单次强直刺激能可靠地诱导出LTP，但复氧70至100分钟后给予强直刺激则无法诱导出LTP。当在缺氧期间给予100μmol/L的竞争性NMDAR拮抗剂D，L-氨基膦酸戊酸（APV）时，复氧100分钟后给予的强直刺激可产生持久的突触增强。缺氧后给予APV并不能阻断缺氧的延迟效应。同样，当在缺氧期间给予一氧化氮合酶抑制剂时，可克服其对LTP诱导的延迟效应，但在缺氧后给予则无效。这些结果表明，缺氧期间NMDAR的过早激活和一氧化氮释放会延迟抑制LTP的诱导，并可能与脑缺氧后出现的记忆缺陷有关。
