Ayala-Grosso C A, Urbina-Paez R
Laboratory of Biochemistry, School of Pharmacy, Universidad Central de Venezuela, Caracas.
J Neurosci Res. 1999 Jan 15;55(2):178-86. doi: 10.1002/(SICI)1097-4547(19990115)55:2<178::AID-JNR5>3.0.CO;2-U.
A cholinergically disrupted laboratory animal has been produced by administration of the cholinotoxin ethylcholine aziridinium mustard (AF64A), which produced a dysfunction in the cholinergic forebrain system. After AF64A treatment, a reduction of choline acetyl transferase (ChAT) activity was measured in the hippocampal regions. ChAT activity was preferentially reduced in tissue samples of the dorsal with respect to the ventral hippocampus, and concomitantly with this reduction, a compensatory increase in ChAT activity in the medial septum was found. Tissue gamma-aminobutyric acid (GABA) content in the hippocampal and septal brain areas was not affected by AF64A, indicating a specific effect on the cholinergic septohippocampal projection. The rate of GABA accumulation induced by aminooxyacetic acid administration was higher in the dorsal hippocampus and medial septum of AF64A-treated animals, but not in their ventral hippocampus and lateral septum, where significant changes occurred in ChAT activity. Concomitantly with the changes in GABA metabolism, a significant Bmax increase and Kd reduction of 3H-flunitrazepam binding in the hippocampus of AF64A-treated animals were associated with changes in the ChAT activity. This finding suggests an increase of GABA input on the cholinergic somas of the medial septum and an uncompensated GABAergic interneuron activity in the hippocampus. In this study, we present an adaptive mechanism of homotypic compensatory metabolism by cholinergic somas, and a heterotypic response of the GABAergic septohippocampal projection system, which was elicited by AF64A administration.
通过给予胆碱毒素氮丙啶基芥子酰基乙基胆碱（AF64A）制备了一种胆碱能功能紊乱的实验动物，该毒素导致胆碱能前脑系统功能障碍。AF64A处理后，测量了海马区域胆碱乙酰转移酶（ChAT）的活性降低。相对于腹侧海马，背侧组织样本中的ChAT活性优先降低，并且伴随着这种降低，在内侧隔区发现ChAT活性有代偿性增加。海马和隔区脑区的组织γ-氨基丁酸（GABA）含量不受AF64A影响，表明对胆碱能隔海马投射有特异性作用。在AF64A处理的动物的背侧海马和内侧隔区，由氨基氧乙酸给药诱导的GABA积累速率较高，但在其腹侧海马和外侧隔区则不然，在这些区域ChAT活性发生了显著变化。伴随着GABA代谢的变化，AF64A处理的动物海马中3H-氟硝西泮结合量的显著Bmax增加和Kd降低与ChAT活性的变化相关。这一发现表明内侧隔区胆碱能神经元体上的GABA输入增加，而海马中GABA能中间神经元活性未得到代偿。在本研究中，我们展示了胆碱能神经元体的同型代偿性代谢的适应性机制，以及由AF64A给药引发的GABA能隔海马投射系统的异型反应。
