Enhancement of LTP in Aged Rats is Dependent on Endogenous BDNF
Enhancement of LTP in Aged Rats is Dependent on Endogenous BDNF
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DOI：
10.1038/npp.2011.64
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发表时间：
2011-08-01
影响因子：
7.6
通讯作者：
Sebastiao, Ana M.
中科院分区：
文献类型：
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作者：
Diogenes, Maria J.;Costenla, Ana R.;Sebastiao, Ana M.
脑源性神经营养因子（BDNF）可促进长时程增强（LTP）的发生，它被认为是学习和记忆的神经生理学基础，当LTP被弱θ波刺激诱发时，这种作用更加明显，并依赖于腺苷A（2A）受体（A（2A）R）的共激活，而腺苷A（2A）受体在老年大鼠中表达更多。由于θ爆发刺激也有利于老年动物的LTP，我们假设，增强的LTP在老化可能与BDNF的神经调节的变化。在36 ~ 38周龄和70 ~ 80周龄大鼠海马脑片中，弱θ波刺激引起的CA 1 LTP幅度显著高于4周龄或10 ~ 15周龄大鼠脑片中的LTP幅度;这种增强不影响认知改善，因为老年大鼠显示出对大脑皮层依赖性学习和记忆表现的损害，如通过Morris水迷宫测试所评估的。BDNF的清除剂TrkB-Fc和Trk磷酸化的抑制剂K252 a减弱了70 - 80周龄大鼠脑片的LTP，但对10 - 15周龄大鼠没有影响。当外源性添加BDNF时，BDNF显著增加了4周龄和10至15周龄大鼠脑片的LTP，但没有进一步增加36至38周龄或70至80周龄大鼠的LTP。A（2A）R拮抗剂SCH 58261（7-（2-苯乙基）-5-氨基-2-（2-呋喃基）-吡唑并[4，3-e] 1，2，4-三唑并[1，5-c]嘧啶）可阻断外源性BDNF对LTP的影响。这些结果表明，在老化时观察到的更高的LTP幅度，这并不转化为改善的空间记忆性能，是内源性BDNF的紧张作用增加的结果。Neuropsychopharmacology（2011）36，1823-1836; doi：10.1038/npp.2011.64; 2011年4月27日在线发表
Long-term potentiation (LTP), considered the neurophysiological basis for learning and memory, is facilitated by brain-derived neurotrophic factor (BDNF), an action more evident when LTP is evoked by weak theta-burst stimuli and dependent on co-activation of adenosine A(2A) receptors (A(2A)R), which are more expressed in aged rats. As theta-burst stimuli also favor LTP in aged animals, we hypothesized that enhanced LTP in aging could be related to changes in neuromodulation by BDNF. The magnitude of CA1 LTP induced by a weak theta-burst stimuli delivered to the Schaffer collaterals was significantly higher in hippocampal slices taken from 36 to 38 and from 70 to 80-week-old rats, when compared with LTP magnitude in slices from 4 or 10 to 15-week-old rats; this enhancement does not impact in cognitive improvement as aged rats revealed an impairment on hippocampal-dependent learning and memory performance, as assessed by the Morris water maze tests. The scavenger for BDNF, TrkB-Fc, and the inhibitor of Trk phosphorylation, K252a, attenuated LTP in slices from 70 to 80-week-old rats, but not from 10 to 15-week-old rats. When exogenously added, BDNF significantly increased LTP in slices from 4 and 10 to 15-week-old rats, but did not further increased LTP in 36 to 38 or 70 to 80-week-old rats. The effects of exogenous BDNF on LTP were prevented by the A(2A)R antagonist, SCH58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine). These results indicate that the higher LTP magnitude observed upon aging, which does not translate into improved spatial memory performance, is a consequence of an increase in the tonic action of endogenous BDNF. Neuropsychopharmacology (2011) 36, 1823-1836; doi:10.1038/npp.2011.64; published online 27 April 2011