ACETYLATED TUBULIN IN DEVELOPING AND AGING RAT BRAIN

神经元的功能和可塑性需要稳定 某些微管群体，以及制造新的 微管 微管也是维持 成熟的神经元形式和功能。 老化中观察到的脱落 大脑（树突棘的丧失，可塑性的丧失）可能是由于 微管稳定性的异常调节。 因此， 神经元形式和功能的调节将至少部分地依赖于 在理解调控微管组装的机制， 稳定 微管由乙酰化的微管蛋白组成 已经被证明更加稳定。 为了确定微管蛋白 乙酰化调节神经元中微管的稳定性，我们将 乙酰化体外脑微管，并确定其 冷稳定性直接或间接地由于影响而改变， 微管相关蛋白的结合。 微管或 对含有乙酰化微管蛋白的结构进行形态学分析， 免疫化学和生物化学上已经在冷稳定级分中 在牛脑匀浆中鉴定为富含乙酰化 微管蛋白 对于总图谱，我们将定量总和乙酰化 微管蛋白和调节微管蛋白水平的酶， 出生后大鼠脑发育、成熟和衰老。实验 例如这些，试图确定 神经元微管组装，对于理解 调节正常神经元的形式和功能，以及这些可能是如何 在年老和患病的大脑中改变。

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.