Wagner A P, Schmoll H, Badan I, Platt D, Kessler C
Department of Neurology, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
Exp Gerontol. 2000 Dec;35(9-10):1211-27. doi: 10.1016/s0531-5565(00)00154-6.
The ability of the rodent brain to support plasticity-related phenomena declines with increasing age. A decreased coordination of genes implicated in brain plasticity may be one factor contributing to this decline. Synaptic rearrangement that occurs after seizure activity is regarded as a model of brain plasticity. In a rat model of seizure-related brain plasticity, we found that the induction of immediate-early genes, as exemplified by c-fos and tissue plasminogen activator (TPA) is not impaired in the aged rat brain. However, the aged rat brain responded more slowly to chemically induced seizure and the levels of c-fos and TPA mRNAs induction are decreased in the cortex and in the hippocampus of 30-month-old rats, as compared to the levels expressed by 3-month-old rats. In addition, at the peak induction the TPA transcripts were restricted to certain cortical layers of the older rats. Surprisingly, in applying the same experimental paradigm to late genes we found that there was a shift toward earlier times in the maximum expression of growth-related molecule, the microtubule-associated protein 1B (MAP1B) mRNA, which was very evident in 18-month-old rats. Aberrant immunolabeling of MAP1B occurred in cortical layer VI of the aged rats where, unlike in young rats, there was heavy staining of neuronal somata. These results suggest that (i) one consequence of aging, besides decreases in the levels of mRNA, is a progressive loss of coordination in gene activity following the administration of a stimulus; (ii) since c-fos, TPA and MAP1B have been implicated in neuronal plasticity, these findings could explain, in part, the limited plasticity of the aging brain.
啮齿动物大脑支持可塑性相关现象的能力会随着年龄的增长而下降。参与大脑可塑性的基因协调性降低可能是导致这种下降的一个因素。癫痫发作活动后发生的突触重排被视为大脑可塑性的一种模型。在一个与癫痫相关的大脑可塑性大鼠模型中，我们发现，以c-fos和组织型纤溶酶原激活剂（TPA）为例的立即早期基因的诱导在老年大鼠大脑中并未受损。然而，老年大鼠大脑对化学诱导的癫痫发作反应更慢，与3月龄大鼠相比，30月龄大鼠大脑皮层和海马中c-fos和TPA mRNA的诱导水平降低。此外，在诱导高峰期，TPA转录本仅限于老年大鼠的某些皮层。令人惊讶的是，在将相同的实验范式应用于晚期基因时，我们发现与生长相关分子微管相关蛋白1B（MAP1B）mRNA的最大表达时间提前，这在18月龄大鼠中非常明显。老年大鼠皮层VI层出现了MAP1B的异常免疫标记，与年轻大鼠不同，该层神经元胞体有大量染色。这些结果表明：（i）衰老的一个后果，除了mRNA水平降低外，是在给予刺激后基因活性的协调性逐渐丧失；（ii）由于c-fos、TPA和MAP1B与神经元可塑性有关，这些发现可以部分解释衰老大脑可塑性有限的原因。
