Gu Z, Yu J, Perez-Polo J R
Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch at Galveston, 301 University Blvd. , Galveston, TX 77555-0652, USA.
Brain Res. 1998 Aug 10;801(1-2):190-7. doi: 10.1016/s0006-8993(98)00579-4.
There are deficits in cholinergic basal forebrain neurons (CBFNs) in the aged brain and patients suffering Alzheimer's disease associated with a partial loss of the CBFNs. To mimic this partial loss and assess its long term effects on residual cholinergic activity and resultant target-derived nerve growth factor (NGF) levels, we produced a partial immunolesion to CBFNs with 192 IgG-saporin, an immunotoxin selectively taken up by p75NTR-bearing neurons. We measured two cholinergic markers, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity, and NGF protein levels at 10 days, 1, 6 and 12 months postlesion. There were no significant changes in the cholinergic markers and the NGF protein levels in the sham-treated animal controls during the one year experiment. Ten days after 192 IgG-saporin treatment, ChAT activity decreased to 35-50% of controls in the olfactory bulb, hippocampus, and cortex. There was a minor but significant recovery of ChAT activity one year after the immunolesion in the hippocampus. Changes in AChE activity mirrored the ChAT changes but were less robust. There were transient increases in NGF protein levels in the hippocampus and cortex that returned to basal levels at 6 months and 12 months postlesion, respectively. In summary, partial immunolesions resulted in partial region-specific and time-dependent recoveries of cholinergic activity in the target areas of the basal forebrain after a partial elimination of CBFNs and a return to basal levels of NGF protein consistent with the hypothesis that the remaining CBFNs compensated for losses of ChAT and NGF due to changes in cholinergic innervation of basal forebrain target areas.
衰老大脑以及患有阿尔茨海默病的患者的胆碱能基底前脑神经元（CBFNs）存在缺陷，且与CBFNs的部分丧失有关。为了模拟这种部分丧失并评估其对残余胆碱能活性以及由此产生的靶源性神经生长因子（NGF）水平的长期影响，我们用192 IgG-皂草素对CBFNs进行了部分免疫损伤，192 IgG-皂草素是一种被携带p75NTR的神经元选择性摄取的免疫毒素。我们在损伤后10天、1个月、6个月和12个月测量了两种胆碱能标志物，即胆碱乙酰转移酶（ChAT）和乙酰胆碱酯酶（AChE）的活性，以及NGF蛋白水平。在为期一年的实验中，假手术处理的动物对照组的胆碱能标志物和NGF蛋白水平没有显著变化。192 IgG-皂草素处理10天后，嗅球、海马体和皮质中的ChAT活性降至对照组的35%-50%。免疫损伤一年后，海马体中的ChAT活性有轻微但显著的恢复。AChE活性的变化与ChAT的变化相似，但程度较弱。海马体和皮质中的NGF蛋白水平有短暂升高，分别在损伤后6个月和12个月恢复到基础水平。总之，部分免疫损伤导致在部分消除CBFNs后，基底前脑靶区域的胆碱能活性出现部分区域特异性和时间依赖性的恢复，并且NGF蛋白水平恢复到基础水平，这与以下假设一致，即剩余的CBFNs补偿了由于基底前脑靶区域胆碱能神经支配变化导致的ChAT和NGF的损失。
