Cannabinoid receptors involved in descending inhibition on spinal seizure-like activity in the phrenic output

Cannabinoid receptors involved in descending inhibition on spinal seizure-like activity in the phrenic output
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DOI:
10.2220/biomedres.44.41
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发表时间:
2023-01-01
影响因子:
1.2
通讯作者:
Izumizaki, Masahiko
Izumizaki, Masahiko
中科院分区:
医学4区
文献类型:
--
作者:
Lin, Shih Tien;Iizuka, Makito;Izumizaki, Masahiko

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在新生啮齿类动物的脑干-脊髓制备中,阻断GABAA和/或甘氨酸受体可诱导癫痫样爆发活动。我们发现这并不适用于膈神经,而一种新的抑制性下降通路可能抑制膈神经的癫痫样活动。实验采用新生大鼠(0-1日龄)的脑干-脊髓制备。同时记录左膈神经和右膈神经C4活动。当10 μ M双管碱和10 μ M士的宁(Bic+Str)阻断GABAA和甘氨酸受体时,第四颈腹根(C4)出现癫痫样爆发活动,膈神经未出现。在C1处作横切面后,C4和膈神经的吸气爆发活动均消失,而两种神经均出现癫痫样活动。我们假设除了通过GABAA和/或甘氨酸受体(从髓质到脊髓)的抑制性下降途径外,抑制性下降途径可以避免癫痫样活动对正常呼吸相关膈肌收缩的干扰。我们发现大麻素受体拮抗剂AM251对脑干-脊髓制备中膈神经Bic+Str诱导癫痫样活动有效。大麻素受体可能参与了这种下降抑制系统。
Seizure-like burst activities are induced by blockade of GABAA and/or glycine receptors in various spinal ventral roots of brainstem-spinal cord preparation from neonatal rodents. We found that this is not applicable to the phrenic nerve and that a new inhibitory descending pathway may suppress seizure-like activity in the phrenic nerve. Experiments were performed in brainstem-spinal cord preparation from newborn rats (age: 0-1 day). Left phrenic nerve and right C4 activities were recorded simultaneously. When GABAA and glycine receptors were blocked by 10 mu M bicuculline and 10 mu M strychnine (Bic+Str), seizure-like burst activities appeared in the fourth cervical ventral root (C4) but not the phrenic nerve. After making a transverse section at C1, the inspiratory burst activity disappeared from both C4 and the phrenic nerve, whereas seizure-like activity appeared in both nerves. We hypothesized that inhibitory descending pathways other than those via GABAA and/or glycine receptors (from the medulla to the spinal cord) work to avoid disturbance of regular respiratory-related diaphragm contraction by seizure-like activity. We found that cannabinoid receptor antagonist, AM251 was effective for the induction of seizure-like activity by Bic+Str in the phrenic nerve in brainstem-spinal cord preparation. Cannabinoid receptors may be involved in this descending inhibitory system.