Stone D J, Rozovsky I, Morgan T E, Anderson C P, Lopez L M, Shick J, Finch C E
Department of Biological Sciences, Andrus Gerontology Center, Los Angeles, California 90089-0191, USA.
Exp Neurol. 2000 Sep;165(1):46-57. doi: 10.1006/exnr.2000.7455.
Age and estrogen treatment influenced fiber outgrowth and compensatory neuronal sprouting after unilateral entorhinal cortex lesions (ECL) which model Alzheimer disease-like deafferentation in the dentate gyrus of the hippocampus. In young F344 rats (3 months old), ovariectomy (OVX) decreased reactive fiber outgrowth by 60%. Sprouting in middle-aged rats (18 months old) was reduced in intact females; no further reduction was caused by OVX. Several astrocyte mRNAs were measured in the dentate gyrus of young and middle-aged female rats in three different estrogen states (sham OVX, OVX, or OVX + estradiol) 1 week after ECL. Glial fibrillary acidic protein (GFAP) mRNA was twofold greater in middle-aged rats than young, although both ages showed threefold increases in response to ECL. In prior studies GFAP was found to be decreased by estradiol treatment 3-4 days after ECL; in this study GFAP mRNA had returned to sham OVX levels in young rats by 7 days post-ECL. Surprisingly, estradiol treatment increased GFAP mRNA levels by 25% above OVX in middle-aged rats. Apolipoprotein E (apoE) mRNA was decreased 20% by age in the dentate, although both age groups showed a 25% increase in apoE mRNA in response to ECL. Apolipoprotein J (apoJ) mRNA was increased 20% in the dentate gyrus of middle-aged rats, and both age groups responded to ECL with a 65% increase in apoJ mRNA. The estrogen state did not alter levels of either apolipoprotein mRNA in the deafferented dentate. The data suggest that the estrogen-induced decrease of GFAP in response to lesions does not persist at 7 days post-ECL during sprouting. Overall effects of age on the dentate gyrus include elevated GFAP mRNA and decreased apoE mRNA. The cortical wound site showed consistent enhancement of GFAP mRNA in both age groups by estradiol above sham OVX and greater responses in middle-aged rats.
年龄和雌激素治疗会影响单侧内嗅皮质损伤（ECL）后的纤维生长和代偿性神经元发芽，ECL可模拟海马齿状回中类似阿尔茨海默病的传入神经阻滞。在年轻的F344大鼠（3个月大）中，卵巢切除术（OVX）使反应性纤维生长减少了60%。中年大鼠（18个月大）中，完整雌性大鼠的发芽减少；OVX并未导致进一步减少。在ECL后1周，对处于三种不同雌激素状态（假手术OVX、OVX或OVX + 雌二醇）的年轻和中年雌性大鼠的齿状回中几种星形胶质细胞mRNA进行了检测。中年大鼠的胶质纤维酸性蛋白（GFAP）mRNA比年轻大鼠高两倍，尽管两个年龄段在ECL后均显示出三倍的增加。在先前的研究中发现，ECL后3 - 4天，雌二醇治疗可使GFAP降低；在本研究中，年轻大鼠在ECL后7天，GFAP mRNA已恢复到假手术OVX水平。令人惊讶的是，雌二醇治疗使中年大鼠的GFAP mRNA水平比OVX组高出25%。载脂蛋白E（apoE）mRNA在齿状回中随年龄增长降低20%，尽管两个年龄组在ECL后apoE mRNA均增加25%。载脂蛋白J（apoJ）mRNA在中年大鼠的齿状回中增加20%，两个年龄组在ECL后apoJ mRNA均增加65%。雌激素状态并未改变去传入神经的齿状回中任何一种载脂蛋白mRNA的水平。数据表明，雌激素诱导的损伤后GFAP减少在发芽期ECL后7天并不持续。年龄对齿状回的总体影响包括GFAP mRNA升高和apoE mRNA降低。在两个年龄组中，皮质伤口部位经雌二醇处理后GFAP mRNA均比假手术OVX组持续增强，且中年大鼠的反应更大。
