• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Sensorimotor Learning/Plasticity

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Pregabalin decreased D-serine content and inhibited NMDA receptor-mediated synaptic transmission in the mouse spinal cord

  • P3-104
  • 浅川 徹也 / Tetsuya Asakawa:1 松澤 理恵 / Rie Matsuzawa:1 高薄 敏史 / Toshifumi Takasusuki:1 前川 正夫 / Masao Maekawa:1 山口 重樹 / Shigaki Yamaguchi:1 堀 雄一 / Yuuichi Hori:1 
  • 1:獨協医科大学・生理学(生体情報) / Dept. Physiol. & Biol. Inf., Dokkyo Med. Univ., Tochigi, Japan 

Pregabalin (PGB) is used to relieve neuropathic pain. We have previously reported that PGB not only acts on presynaptic calcium channels but also directly acts on exocytotic machinery, and thereby inhibits transmitter release (2013). In the present experiments, we have studied the effects of PGB on D-serine content and NMDA receptor-mediated synaptic transmission in the spinal cord dorsal horn. Under halothane anesthesia, ICR mice were subjected to partial sciatic nerve ligation according to Seltzer et al. (1990). We evaluated mechanical allodynia using von Frey filaments. PGB (30-50 mg/kg body weight) was intraperitonealy (IP) injected daily for 5-7 days. It was observed that IP injection of PGB decreased the paw withdrawal frequency to von Frey stimuli. For the measurement of D-serine concentration, the lumbar spinal cord was removed under halothane anesthesia, homogenized, and ultra-filtrated. D-serine concentration in the spinal cord was assessed by using liquid chromatography-mass spectrometry. For electrophysiological experiments, lumbar spinal slices were prepared and tight-seal whole-cell recordings were made from superficial dorsal horn neurons. Non-NMDA and NMDA receptor-mediated glutamatergic excitatory postsynaptic currents (EPSCs) were analyzed. Partial litation of the sciatic nerve increased the concentration of D-serine in the spinal cord significantly, increased the ratio of the amplitude of NMDA-EPSCs to that of non-NMDA-EPSCs (NMDA/non-NMDA ratio), and lengthened the decay time course of NMDA-EPSCs. IP injection of PGB in the nerve-ligated mice decreased the D-serine concentration in the spinal cord, decreased the NMDA/non-NMDA ratio, and shortened the decay phase of NMDA-EPSCs. These observations suggest that PGB decreases D-serine concentration in the spinal cord, mechanisms for which are presently known, and thereby affects NMDA receptor-mediated synaptic transmission in the superficial dorsal horn.

Copyright © Neuroscience2014. All Right Reserved.