Costenla A R, de Mendonça A, Ribeiro J A
Laboratory of Neurosciences, Faculty of Medicine of Lisbon, Portugal.
Brain Res. 1999 Dec 18;851(1-2):228-34. doi: 10.1016/s0006-8993(99)02194-0.
Adenosine is known to modulate synaptic plasticity in the hippocampus of young animals through activation of adenosine A1 receptors. The objective of the present study is to investigate whether the modulatory role of adenosine on phenomena of synaptic plasticity is maintained or modified in the hippocampus of aged animals. We compared the effects of the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50 nM), on paired-pulse facilitation (PPF), long-term depression (LTD), long-term potentiation (LTP) and depotentiation elicited in hippocampal slices taken from young adult (5-6 weeks) and old (2 years old) male Wistar rats. DPCPX attenuated PPF both in young (1.64 +/- 0.05 vs. 1.76 +/- 0.05%, n = 6) and in old rats (1.33 +/- 0.05 vs. 1.55 +/- 0.1%, n = 6). LTD was only observed in the presence of DPCPX in both young (21.3 +/- 0.6%, n = 4) and old rats (14.4 +/- 0.9%, n = 6). LTP induced by high-frequency stimulation (HFS) was not significantly different in young and old animals, in the presence or in the absence of DPCPX. A larger depotentiation was observed in the presence of DPCPX in young rats (27.6 +/- 4.4% vs. 16.8 +/- 4.7%, n = 7) as well as in old rats (41.3 +/- 5.1% vs. 16.1 +/- 2.7%, n = 6). LTP induced by theta-burst stimulation was observed only in the presence of DPCPX (53.9 +/- 4.9%, n = 5) in young rats, but could be obtained either in the control solution (81.8 +/- 17.9%, n = 7) or in the presence of DPCPX (98.5 +/- 24.2%, n = 7) in old rats. The modulatory role of endogenous adenosine on synaptic plasticity is generally maintained in aged animals. Drugs interfering with adenosine A1 receptor effects could then be used in old animals to modify synaptic plasticity with relevant behavioural consequences.
已知腺苷可通过激活腺苷A1受体来调节幼龄动物海马体中的突触可塑性。本研究的目的是调查在老龄动物的海马体中，腺苷对突触可塑性现象的调节作用是否得以维持或改变。我们比较了选择性腺苷A1受体拮抗剂1,3 - 二丙基 - 8 - 环戊基黄嘌呤（DPCPX，50 nM）对从年轻成年（5 - 6周）和老年（2岁）雄性Wistar大鼠获取的海马体切片中诱发的双脉冲易化（PPF）、长时程抑制（LTD）、长时程增强（LTP）和去增强作用的影响。DPCPX在年轻大鼠（1.64±0.05对1.76±0.05%，n = 6）和老年大鼠（1.33±0.05对1.55±0.1%，n = 6）中均减弱了PPF。仅在DPCPX存在的情况下，年轻大鼠（21.3±0.6%，n = 4）和老年大鼠（14.4±0.9%，n = 6）中均观察到了LTD。在有或没有DPCPX存在的情况下，高频刺激（HFS）诱导的LTP在年轻和老年动物中无显著差异。在DPCPX存在的情况下，年轻大鼠（27.6±4.4%对16.8±4.7%，n = 7）和老年大鼠（41.3±5.1%对16.1±2.7%，n = 6）中均观察到了更大程度的去增强作用。仅在DPCPX存在的情况下，年轻大鼠中观察到了theta爆发刺激诱导的LTP（53.9±4.9%，n = 5），但在老年大鼠中，在对照溶液（81.8±17.9%，n = 7）或DPCPX存在的情况下（98.5±24.2%，n = 7）均可获得。内源性腺苷对突触可塑性的调节作用在老龄动物中通常得以维持。干扰腺苷A受体效应的药物可用于老龄动物，以改变突触可塑性并产生相关行为后果。
