Astrocyte-neuron lactate shuttle, the major effector of astrocytic PACAP signaling for CNS functions

  • Kambe Yuki
    Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University
  • Kurihara Takashi
    Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University
  • Miyata Atsuro
    Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University

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  • PACAPシグナリングによって駆動されるアストロサイト―ニューロン乳酸シャトルの中枢神経機能発現への寄与―
  • PACAP シグナリング ニ ヨッテ クドウ サレル アストロサイト : ニューロン ニュウサン シャトル ノ チュウスウ シンケイ キノウ ハツゲン エ ノ キヨ

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Abstract

<p>Transfer of lactate from astrocytes to neurons is activated when synaptic activity is increased, and this mechanism is now known as the astrocyte-neuron lactate shuttle (ANLS), that could account for the coupling between synaptic activity and energy delivery. Many lines of evidence suggested that ANLS contributes to neuronal activation or synaptic plasticity at the cellular level as well as learning/memory and cocaine addiction at the behavioral level. However, the candidate neurotransmitters which evoke ANLS activation are still under discussion. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neurotransmitter which distributed widely in central nervous system. Since PACAP might activate ANLS from very low concentration in cultured forebrain astrocytes, PACAP might be one of the candidates for the endogenous ANLS activator. In the present study, we investigated the potential relevance of PACAP/ANLS signaling in the learning/memory and spinal nociceptive transmission. In this study, we made the following findings: 1) PACAP could be an endogenous inducer for ANLS activation in central nervous system; 2) ANLS activation by PACAP/PAC1 receptor signaling contributed to learning/memory and induced long-lasting nociceptive behaviors; 3) PKC activation played an important role in the PACAP/PAC1 receptor-evoked ANLS.</p>

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