Dlugos C A, Pentney R J
Department of Anatomy and Cell Biology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo 14214-3000, USA.
Alcohol Alcohol. 1997 Mar-Apr;32(2):161-72. doi: 10.1093/oxfordjournals.alcalc.a008250.
Clinical symptoms of alcohol abuse may be confused with symptoms of age-related neuropathologies in human patients. It is important, therefore, to determine the relationships between alcohol abuse and changes in brain structures in well-controlled studies of ageing subjects. Currently there is little well-documented information of this type available. The purpose of this study was to determine whether long-term ethanol treatment during ageing would lead to reductions in synaptic input to cerebellar Purkinje neurons (PN) of old F344 rats that: (1) were more severe than those attributable to ageing alone; (2) might be responsible for an ethanol-related deletion of dendritic segments of PN in old F344 rats shown previously in this laboratory. The total number of synapses per PN dendritic arbor was determined after ethanol treatment of old F344 rats for 40 weeks between 12 and 22 months of age and in similarly treated rats given a subsequent 20-week period of recovery between 22 and 27 months of age. Groups of age-matched rats fed a chow diet and water and rats pair-fed an isocaloric liquid diet lacking ethanol served as controls. The volume of the molecular layer per PN arbor and the numerical density of synapses in the molecular layer was determined from light microscopic preparations of a fixed volume of the cerebellar cortex. Photographic montages of the ultrastructure of the molecular layer of the cerebellum were also prepared from each rat for measurements of synaptic numerical densities. From the volume of the molecular layer per PN arbor and the numerical density of synapses in the molecular layer, the total number of synapses per PN arbor was estimated for each rat. There was a significant reduction in synapses in the old ethanol-treated rats relative to age-matched chow-fed rats. There were also significant interactions between recovery and treatment prior to recovery. During recovery, synaptic numbers in the old, ethanol-treated rats were restored to pre-recovery control levels whereas synaptic numbers in the old, chow-fed rats were significantly reduced during the same period of time. There were no significant diet- or age-related changes in synaptic numbers in the pair-fed control rats during treatment or recovery. The pattern of reduction in synaptic numbers during ethanol treatment and restoration of synaptic numbers during recovery from treatment paralleled the pattern of ethanol-related segment loss and recovery-related segment regrowth noted earlier in PN arbors of old F344 rats, suggesting that reductions in the numbers of synapses and deletion of terminal dendritic segments were causally related in this strain.
酒精滥用的临床症状可能会与人类患者中与年龄相关的神经病理学症状相混淆。因此，在对老年受试者进行的严格对照研究中，确定酒精滥用与脑结构变化之间的关系非常重要。目前，这类有充分记录的信息很少。本研究的目的是确定在衰老过程中进行长期乙醇处理是否会导致老年F344大鼠小脑浦肯野神经元（PN）的突触输入减少，具体表现为：（1）比单纯衰老导致的减少更严重；（2）可能是本实验室先前所示老年F344大鼠中与乙醇相关的PN树突段缺失的原因。在12至22月龄的老年F344大鼠接受40周乙醇处理后，以及在22至27月龄的类似处理大鼠随后进行20周恢复期后，测定每个PN树突分支的突触总数。以喂食普通饲料和水的年龄匹配大鼠组以及成对喂食不含乙醇的等热量液体饲料的大鼠作为对照。从固定体积的小脑皮质的光学显微镜标本中测定每个PN树突分支的分子层体积和分子层中突触的数值密度。还从每只大鼠制备小脑分子层超微结构的摄影蒙片，用于测量突触数值密度。根据每个PN树突分支的分子层体积和分子层中突触的数值密度，估算每只大鼠每个PN树突分支的突触总数。与年龄匹配的喂食普通饲料的大鼠相比，老年乙醇处理大鼠的突触显著减少。在恢复之前，恢复与处理之间也存在显著的相互作用。在恢复期间，老年乙醇处理大鼠的突触数量恢复到恢复前的对照水平，而老年喂食普通饲料的大鼠的突触数量在同一时期显著减少。在处理或恢复期间，成对喂食的对照大鼠的突触数量没有与饮食或年龄相关的显著变化。乙醇处理期间突触数量减少的模式以及处理恢复期间突触数量恢复的模式与先前在老年F344大鼠PN树突分支中观察到的与乙醇相关的段丢失和与恢复相关的段再生模式相似，表明在该品系中突触数量减少和终末树突段缺失存在因果关系。
