Whitehouse P J, Lynch D, Kuhar M J
J Neurochem. 1984 Aug;43(2):553-9. doi: 10.1111/j.1471-4159.1984.tb00934.x.
Studies of neurotransmitter and drug receptor alterations in neurodegenerative disorders have contributed to our understanding of the pathophysiology of these conditions. The effect of postmortem delay in freezing tissue after death and prolonged storage of tissue prior to analysis on receptor binding assays are potential artifacts that may limit interpretation of the effects of disease on receptor populations. We used a rat model of the human autopsy process to study the effects of increasing postmortem delay and storage time on N-methylscopolamine (NMS), p-aminoclonidine (PAC), flunitrazepam (FLU), and spiperone binding in a variety of rat brain regions. The rat brains were cooled using a temperature-controlled environment and thermistor probe to follow cooling curves obtained in human brain. Brains were cooled to either room temperature (22 degrees C) or refrigerator temperature (4 degrees C). For three of the four receptors, receptor binding decreased as postmortem delay before freezing increased, particularly in tissue cooled to room temperature. Unlike binding at other receptor sites, FLU binding increased with increasing postmortem delay to freezing. Different effects on KD and Bmax were noted for each ligand studied. No effects of the freezing process itself or storage at -80 degrees C were detectable.
对神经退行性疾病中神经递质和药物受体改变的研究有助于我们理解这些病症的病理生理学。死后冷冻组织的延迟时间以及分析前组织的长时间储存对受体结合测定的影响是潜在的假象，可能会限制对疾病对受体群体影响的解释。我们使用人类尸检过程的大鼠模型，研究死后延迟时间增加和储存时间对多种大鼠脑区中N - 甲基东莨菪碱（NMS）、对氨基可乐定（PAC）、氟硝西泮（FLU）和螺哌隆结合的影响。使用温度控制环境和热敏电阻探头冷却大鼠大脑，以跟踪在人类大脑中获得的冷却曲线。将大脑冷却至室温（22摄氏度）或冰箱温度（4摄氏度）。对于四种受体中的三种，冷冻前的死后延迟增加时，受体结合减少，特别是在冷却至室温的组织中。与其他受体位点的结合不同，FLU结合随着冷冻前死后延迟的增加而增加。对于所研究的每种配体，观察到对KD和Bmax的不同影响。未检测到冷冻过程本身或在 -80摄氏度储存的影响。
