海人酸处理大鼠海马中的急性树突毒性变化

Acute dendrotoxic changes in the hippocampus of kainate treated rats.

作者信息

Olney J W, Fuller T, de Gubareff T

出版信息

Brain Res. 1979 Oct 26;176(1):91-100. doi: 10.1016/0006-8993(79)90872-2.

Abstract

Kainic acid (KA), a potent neuroexcitatory and neurotoxic analog of glutamate (Glu), induces a widespread pattern of brain damage when administered subcutaneously to adult rats. The hippocampus is among the brain regions most consistently and severely damaged. Here we describe acute swelling of certain spines and branchlets of dendrites as the first detectable sign of KA neurotoxic changes in the hippocampus. These swellings conform to a laminar pattern suggesting selective toxic interaction of KA at specific levels of the dendritic trees of hippocampal pyramidal and dentate granule neurons. The frequency and severity of involvement of each type of hippocampal neuron at each level of its dendritic tree was roughly estimated and neuronal types were ranked from the most to least extensively involved (CA3 greater than CA4 greater than CA1 greater than CA2 greater than dentate granules). The same rank order has been described for the vulnerability of these neurons to acute destruction following intraventricular KA administration. Because the pattern of dendritic dilatations observed corresponds well with the pattern of termination of putative glutamergic inputs to the hippocampus, we interpret the findings as being consistent with the hypothesis that the toxic effects of KA are mediated through glutamergic excitatory receptors. We propose that the sensitivity of a given neuron to the neurodestructive action of KA may be determined by the percentage of its dendritic surface occupied by Glu receptors. We suspect that most, if not all, hippocampal neurons receive some glutamergic input and, therefore, are sensitive to KA. That CA3 pyramids are substantially more sensitive than dentate granules may signify that the former receive many more Glu terminals than the latter, an assumption quite consistent with our observation that focal dendritic swellings were both more densely and more widely distributed over the dendritic surfaces of the former than the latter.

摘要

kainic 酸（KA）是谷氨酸（Glu）的一种强效神经兴奋性和神经毒性类似物，当皮下注射给成年大鼠时，会引起广泛的脑损伤模式。海马体是最常受到严重损伤的脑区之一。在这里，我们描述了某些树突棘和小分支的急性肿胀，这是海马体中 KA 神经毒性变化的第一个可检测到的迹象。这些肿胀符合层状模式，表明 KA 在海马体锥体细胞和齿状颗粒神经元树突的特定水平上存在选择性毒性相互作用。大致估计了每种海马体神经元在其树突的每个水平上受累的频率和严重程度，并将神经元类型从受累程度最高到最低进行了排序（CA3＞CA4＞CA1＞CA2＞齿状颗粒）。对于这些神经元在脑室内注射 KA 后对急性破坏的易损性，也描述了相同的排序。由于观察到的树突扩张模式与海马体假定的谷氨酸能输入的终止模式非常吻合，我们将这些发现解释为与 KA 的毒性作用通过谷氨酸能兴奋性受体介导的假设一致。我们提出，给定神经元对 KA 神经破坏作用的敏感性可能由其树突表面被 Glu 受体占据的百分比决定。我们怀疑，即使不是全部，大多数海马体神经元都接受一些谷氨酸能输入，因此对 KA 敏感。CA3 锥体神经元比齿状颗粒神经元敏感得多，这可能意味着前者比后者接受更多的 Glu 终末，这一假设与我们的观察结果相当一致，即局灶性树突肿胀在前者的树突表面比后者分布更密集、更广泛。