Levitt P
Department of Anatomy, Medical College of Pennsylvania, Philadelphia 19129.
Cell Tissue Res. 1988 Apr;252(1):175-80. doi: 10.1007/BF00213839.
Pharmacological and anatomical analyses of central monoaminergic and cholinergic neurons were performed in the "tottering" mouse, an autosomal recessive neurologic gene mutation that results in an overproduction of axons of the locus coeruleus and an increase in norepinephrine content in specific terminal fields. Except for the previously reported increase in norepinephrine content, all pharmacological parameters measured, including tyrosine hydroxylase activity, norepinephrine turnover, serotonin content, and choline acetyltransferase activity, in targets hyperinnervated by the locus coeruleus were normal. Immunocytochemical staining for tyrosine hydroxylase demonstrated the pronounced hyperinnervation in the "tottering" brain, whereas both serotonin and choline acetyltransferase immunostaining were similar between "tottering" and wild type. The volume of 3 target areas that are hyperinnervated by the locus coeruleus in the "tottering" mouse, the hippocampus, cerebellum, and cochlear nuclei, were normal. In addition, neuronal number and somal size in the locus coeruleus were found to be unchanged in the mutant genotype. These data demonstrate several features of the effects of the "tottering" gene: 1) compensatory changes in several adrenergic pharmacological parameters do not occur in response to the hyperinnervation of targets by locus coeruleus axons; 2) neither direct effects of the "tottering" gene on, nor compensatory changes in, the extent of cholinergic or serotonergic innervation of several targets of the locus coeruleus appear to occur; and 3) the lack of changes in size of the targets of the locus coeruleus suggest that the hyperinnervation in the "tottering" mouse is due to a direct genetic alteration of axonal growth by the locus coeruleus neurons, rather than to selective shrinkage of targets in the presence of normal terminal arbors.
对“蹒跚”小鼠进行了中枢单胺能和胆碱能神经元的药理学及解剖学分析。“蹒跚”小鼠是一种常染色体隐性神经基因突变体，其蓝斑轴突过度生成，特定终末区域去甲肾上腺素含量增加。除了之前报道的去甲肾上腺素含量增加外，在蓝斑过度支配的靶区中测量的所有药理学参数，包括酪氨酸羟化酶活性、去甲肾上腺素周转率、5-羟色胺含量和胆碱乙酰转移酶活性，均正常。酪氨酸羟化酶的免疫细胞化学染色显示“蹒跚”小鼠脑内有明显的过度支配，而“蹒跚”小鼠和野生型小鼠的5-羟色胺及胆碱乙酰转移酶免疫染色相似。“蹒跚”小鼠中蓝斑过度支配的3个靶区，即海马、小脑和耳蜗核的体积正常。此外，发现突变基因型的蓝斑中神经元数量和胞体大小未发生变化。这些数据证明了“蹒跚”基因效应的几个特点：1）蓝斑轴突对靶区的过度支配不会引起几种肾上腺素能药理学参数的代偿性变化；2）“蹒跚”基因对蓝斑几个靶区的胆碱能或5-羟色胺能神经支配程度似乎既无直接影响，也无代偿性变化；3）蓝斑靶区大小未发生变化，这表明“蹒跚”小鼠中的过度支配是由于蓝斑神经元轴突生长的直接基因改变，而非在正常终末分支存在的情况下靶区的选择性萎缩。
