Edagawa Yoshikuni, Sato Fumiyuki, Saito Hiroshi, Takeda Tadahiro, Shimizu Noriko, Narui Takao, Shibata Shoji, Ito Yoshihisa
Department of Pharmacology, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
Brain Res. 2005 Jan 25;1032(1-2):183-92. doi: 10.1016/j.brainres.2004.11.012.
We have previously found that oral or intravenous (i.v.) administration of the polysaccharide fraction PB-2, extracted from the lichen Flavoparmelia baltimorensis, facilitated the induction of long-term potentiation (LTP) in the dentate gyrus (DG) in vivo. In this study, the mechanism underlying the effect of PB-2 on the induction of LTP was investigated in the DG of anesthetized rat focusing on the contribution of the interleukin-1 (IL-1) receptor and the adrenaline beta-receptor. An i.v. injection of IL-1ra (10(-9) g/kg), an antagonist of the IL-1 receptor, had no effect on the basal response in the DG; however, this treatment augmented the enhancement of LTP induced by a single i.v. injection of PB-2 (10(-3) g/kg). This potentiating effect was also observed following intracerebroventricular (i.c.v.) injection of IL-1ra (10(-15)-10(-11) g). An i.v. injection of IL-1beta (3.5 x 10(-15)-3.5 x 10(-9) g/kg) inhibited the induction of LTP, which was diminished by the previous application of IL-1ra. These results suggest that the activation of the IL-1 receptor induces the suppression of LTP in PB-2-treated rats, and that endogenous IL-1beta contributes to the IL-1 receptor activation. An i.c.v. infusion of metoprolol (7.5 x 10(-6) g), an antagonist of the adrenaline beta(1)-receptor, attenuated the enhancement of LTP induced by an i.v. injection of PB-2. These results suggest that PB-2 has two different effects on the LTP, an enhancing effect and an inhibiting one, and that it exhibited the significant enhancing effect on the LTP as a total balance of these effects.
我们之前发现,口服或静脉注射从地衣巴尔的摩黄髓盘衣中提取的多糖组分PB-2,可促进体内齿状回(DG)中长时程增强(LTP)的诱导。在本研究中,以白细胞介素-1(IL-1)受体和肾上腺素β受体的作用为重点,在麻醉大鼠的DG中研究了PB-2诱导LTP的作用机制。静脉注射IL-1受体拮抗剂IL-1ra(10(-9) g/kg)对DG中的基础反应无影响;然而,该处理增强了单次静脉注射PB-2(10(-3) g/kg)诱导的LTP增强。脑室内注射IL-1ra(10(-15)-10(-11) g)后也观察到这种增强作用。静脉注射IL-1β(3.5×10(-15)-3.5×10(-9) g/kg)抑制LTP的诱导,而先前应用IL-1ra可减弱这种抑制作用。这些结果表明,IL-1受体的激活在PB-2处理的大鼠中诱导LTP的抑制,内源性IL-1β参与IL-1受体的激活。脑室内注入肾上腺素β(1)受体拮抗剂美托洛尔(7.5×10(-6) g)减弱了静脉注射PB-2诱导的LTP增强。这些结果表明,PB-2对LTP有两种不同的作用,一种增强作用和一种抑制作用,并且它作为这些作用的总体平衡对LTP表现出显著的增强作用。