ACETYLATED TUBULIN IN DEVELOPING AND AGING RAT BRAIN

神经元的功能和可塑性需要稳定的能力 某些微管种群，以及制造新的 微管。微管也是维持心脏功能的关键。 成熟的神经元形态和功能。在衰老过程中观察到的异常 脑部(树突棘丧失、可塑性丧失)可能是由 微管稳定性的异常调节。从而理解了 神经元形态和功能的调节将至少部分取决于 在理解调节微管组装和 稳定性。由乙酰化的微管蛋白组成的微管 已经被证明更稳定。确定微管蛋白是否 乙酰化调节神经元中微管的稳定性，我们将 体外乙酰化脑微管，并测定其 冷稳定性直接或间接地由于影响而改变 关于微管相关蛋白的结合。微管或 含有乙酰化微管蛋白的结构将进行形态分析， 免疫化学和生物化学已经在冷稳定组分 在牛脑匀浆中被鉴定为富含乙酰化 微管蛋白。对于总配置文件，我们将量化总和乙酰化 微管蛋白，以及调节后者水平的酶，在 出生后大鼠脑的发育、成熟和衰老。实验 如这些，试图确定监管机制 神经元微管组装，对于理解 对正常神经元形态和功能的调节，以及它们可能是如何发生的 在衰老和患病的大脑中发生改变。

Neuronal function and plasticity require the capacity to stabilize certain microtubule populations, as well as the ability to make new microtubules. Microtubules are also essential for the maintenance of mature neuronal form and function. Abnormalities observed in aging brain (loss of dendritic spines, loss of plasticity) may result from abnormal modulation of microtubule stability. Thus understanding the regulation of neuronal form and function will depend at least partially in understanding the mechanisms that regulate microtubule assembly and stability. Microtubules comprised of tubulin that has been acetylated have been shown to be more stable. To determine whether tubulin acetylation regulates microtubule stability in neurons, we will acetylate brain microtubules in vitro, and determine whether their cold-stability is altered either directly, or indirectly due to effects on the binding of microtubule-associated proteins. Microtubules or structures containg acetylated tubulin will be analyzed morphologically, immunochemically and biochemically in cold-stable fractions already identified in bovine brain homogenate as enriched for acetylated tubulin. For a total profile, we will quantify total and acetylated tubulin, and the enzymes that regulate the levels of the latter, during postnatal rat brain development, maturation, and senescence. Experiments such as these, that attempt to identify regulatory mechanisms in neuronal microtubule assembly, are essential for understanding the regulation of normal neuronal form and function, and how these may be altered in aged and diseased brain.