Parishin C's prevention of Aβ 1-42-induced inhibition of long-term potentiation is related to NMDA receptors

Abstract

The rhizome of Gastrodia elata (GE), a herb medicine, has been used for treatment of neuronal disorders in Eastern Asia for hundreds of years. Parishin C is a major ingredient of GE. In this study, the i.c.v. injection of soluble Aβ 1-42 oligomers model of LTP injury was used. We investigated the effects of parishin C on the improvement of LTP in soluble Aβ 1-42 oligomer-injected rats and the underlying electrophysiological mechanisms. Parishin C (i.p. or i.c.v.) significantly ameliorated LTP impairment induced by i.c.v. injection of soluble Aβ 1-42 oligomers. In cultured hippocampal neurons, soluble Aβ 1-42 oligomers significantly inhibited NMDAR currents while not affecting AMPAR currents and voltage-dependent currents. Pretreatment with parishin C protected NMDA receptor currents from the damage induced by Aβ. In summary, parishin C improved LTP deficits induced by soluble Aβ 1-42 oligomers. The protection by parishin C against Aβ-induced LTP damage might be related to NMDA receptors.

Keywords: Ion channels; Long-term potentiation; NMDA receptors; Neuroprotection; Parishin C.

Graphical abstract

Figure 1

Chemical structures of gastrodin and parishin C.

Figure 2

Memantine rescued inhibition of LTP induced by soluble Aβ_1–42 oligomers in rats. (A) and (B) showed original traces of PS before (1) and after (2) HFS. (C) 5 mg/kg MK-801 abolished HFS induced LTP (control group n=4; MK-801 group n=5). (D) 2 μmol/L soluble Aβ_1–42 oligomers significantly inhibited LTP (vs. control group, P< 0.05), and 10 mg/kg memantine administrated i.p. in advance rescued this inhibition (control group n=7, Aβ_1–42 group n=5, memantine group n=5). Data were shown as mean ± SEM, ^⁎P<0.05 vs. control group, ^#P< 0.05 vs. Aβ_1–42 group.

Figure 3

Effects of parishin C on inhibition of LTP induced by soluble Aβ_1–42 oligomers in rats. (A) showed original traces of PS before (1) and after (2) HFS in four groups. (B) Parishin C 20 mg/kg was given i.p. for two days before LTP recordings and was given i.p. 10 min before i.c.v. injection of 2 μmol/L soluble Aβ_1–42 oligomers. (C) Parishin C 10 μmol/L was given i.c.v. before 2 μmol/L soluble Aβ_1–42 oligomers injection. HFS was performed 60 min after injection of soluble Aβ_1–42 oligomers in all experiments. Parishin C improved LTP induction significantly after Aβ treatment (P < 0.05). Data were shown as mean ± SEM, control group n=7, Aβ_1–42 group n=5, pC (i.p.) group n=5, pC (i.c.v.) group n=5, ^⁎P < 0.05 vs. control group, ^#P<0.05 vs. Aβ_1–42 group.

Figure 4

Parishin C had no effects on normal LTP and ion channels. (A) Upper traces of PS before (1) and after (2) HFS in two groups. Parishin C 20 mg/kg given i.p. 30 min before HFS did not influence the baseline and LTP induction in normal rats (control group n=8, pC group n=7). (B) Perfusion of 10 μmol/L parishin C for 10 min had no effects on AMPAR currents in primary cultured hippocampal pyramidal neurons. The bars above current recordings show pressure injection of 1 s, 3 μmol/L AMPA (n=3). (C) Perfusion of 10 μmol/L parishin C for 10 min had no effects on NMDAR currents in primary cultured hippocampal pyramidal neurons. The bars above current recordings show pressure injection of 1 s, 100 μmol/L NMDA and 10 μmol/L glycine (n=5). Data were shown in mean±SEM. The amplitudes of all currents were normalized to the first evoked at –70 mV.

Figure 5

10 μmol/L parishin C had no effects on voltage-dependent currents in cultured hippocampal neurons of rats. (A) parishin C (10 μmol/L) had no effects on voltage-dependent total sodium currents (n = 5), holding potential =–80 mV. (B) parishin C (10 μmol/L) had no effects on voltage-dependent total outward potassium currents (n = 3), holding potential = –70 mV. (C) parishin C (10 μmol/L) had no effects on voltage-dependent total calcium currents (n = 3), holding potential =–90 mV. Data are shown in mean ± SEM.

Figure 6

Parishin C protected against inhibition of NMDAR currents by 2 μmol/L soluble Aβ_1–42 oligomers but not AMPAR currents in primary cultured hippocampal neurons. Holding potential was –70 mV and external solution was with 0.1 μmol/L TTX, and without Mg²⁺. (A) Bath perfusion of 2 μmol/L soluble Aβ_1–42 oligomers for 10 min had no effects on AMPAR currents. Short bar means pressure injection of 3 μmol/L AMPA. (B) Bath perfusion of 2 μmol/L soluble Aβ_1–42 oligomers for 10 min inhibited NMDAR currents, and the inhibition continued during wash. Parishin C (10 μmol/L) perfusion 10 min beforehand prevented Aβ’s inhibitory effects. Short bar meant pressure injection of 100 μmol/L NMDA and 10 μmol/L glycine. (C) The AMPAR currents were not changed during soluble Aβ_1–42 oligomers perfusion (n=3). (D) Soluble Aβ_1–42 oligomers significantly inhibited NMDAR currents but it was rescued by perfusion of parishin C (Aβ_1–42 group n=5, pC+ Aβ_1–42 group n=6). ^⁎P<0.05 vs. currents before perfusion, ^#P<0.05 vs. Aβ_1–42 group. Data are mean±SEM. The amplitudes of all currents were normalized to the first evoked at –70 mV.