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首页> 外文期刊>The European Journal of Neuroscience >Astrocyte-derived kynurenic acid modulates basal and evoked cortical acetylcholine release
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Astrocyte-derived kynurenic acid modulates basal and evoked cortical acetylcholine release

机译：星状细胞衍生的犬尿酸调节基础和诱发的皮质乙酰胆碱释放

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We tested the hypothesis that fluctuations in the levels of kynurenic acid (KYNA), an endogenous antagonist of the ? nicotinic acetylcholine (ACh) receptor, modulate extracellular ACh levels in the medial prefrontal cortex in rats. Decreases in cortical KYNA levels were achieved by local perfusion of S-ESBA, a selective inhibitor of the astrocytic enzyme kynurenine aminotransferase II (KAT II), which catalyses the formation of KYNA from its precursor L-kynurenine. At 5 itim, S-ESBA caused a 30% reduction in extracellular KYNA levels, which was accompanied by a two-threefold increase in basal cortical ACh levels. Co-perfusion of KYNA in the endogenous range (100 nwi), which by itself tended to reduce basal ACh levels, blocked the ability of S-ESBA to raise extracellular ACh levels. KYNA perfusion (100 nM) also prevented the evoked ACh release caused by D-amphetamine (2.0 mg/kg). This effect was duplicated by the systemic administration of kynurenine (50 mg/kg), which resulted in a significant increase in cortical KYNA formation. Jointly, these data indicate that astrocytes, by producing and releasing KYNA, have the ability to modulate cortical cholinergic neurotransmission under both basal and stimulated conditions. As cortical KYNA levels are elevated in individuals with schizophrenia, and in light of the established role of cortical ACh in executive functions, our findings suggest that drugs capable of attenuating the production of KYNA may be of benefit in the treatment of cognitive deficits in schizophrenia#1 Dollars 1001N200307785Dollars 1200
机译：我们检验了以下假设，即尿嘧啶β的内源性拮抗剂犬尿酸（KYNA）水平的波动。烟碱乙酰胆碱（ACh）受体调节大鼠前额叶内侧皮质中细胞外ACh的水平。皮质KYNA水平的降低是通过局部灌注S-ESBA（一种星形细胞酶犬尿氨酸氨基转移酶II（KAT II）的选择性抑制剂）来实现的，该酶催化KYNA从其前体L-犬尿氨酸的形成。在5 itim时，S-ESBA导致细胞外KYNA水平降低30％，同时伴随着基础皮层ACh水平升高三倍。内源性范围内（100 nwi）的KYNA共灌注本身倾向于降低基础ACh水平，却阻碍了S-ESBA提高细胞外ACh水平的能力。 KYNA灌注（100 nM）还可以防止D-苯异丙胺（2.0 mg / kg）引起的ACh释放。犬尿氨酸（50 mg / kg）的全身性给药可复制这种作用，从而导致皮质KYNA的形成显着增加。这些数据共同表明，星形胶质细胞通过产生和释放KYNA，在基础和刺激条件下均具有调节皮质胆碱能神经传递的能力。由于精神分裂症患者的皮质KYNA水平升高，并且鉴于皮质ACh在执行功能中已确立的作用，我们的发现表明，能够减弱KYNA产生的药物可能有助于治疗精神分裂症的认知功能障碍＃ 1 Dollars 1001N200307785美元1200

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