Koed K, Linnet K
Institute for Basic Research in Psychiatry, Department of Biological Psychiatry, Psychiatric Hospital in Aarhus, The Aarhus University Hospital, Skovagervej 2, DK-8240, Risskov, Denmark.
Eur Neuropsychopharmacol. 2000 Dec;10(6):501-9. doi: 10.1016/s0924-977x(00)00121-8.
We and others have earlier shown that severe serotonin depletion leads to a compensatory down-regulation in the expression of the serotonin transporter (5HTT) gene. We have now investigated the expression of both the 5HTT and the norepinephrine transporter (NET) gene to assess the possible interaction between the noradrenergic and the serotonergic neurotransmitter systems. Acute severe serotonin depletion induced by p-chlorophenylalanine (PCPA) treatment leads to enhanced NET(Long) mRNA levels and reduced 5HTT mRNA level. This change in transporter mRNA expression was paralleled by a non-significant change in protein expression. Chronic severe serotonin depletion combined with treatment with the antidepressant imipramine leads to enhanced NET(Long) mRNA levels. Acute treatment with the monoamine oxidase A inhibitor clorgyline, acute moderate NE reduction (alpha-methyl-p-tyrosine treatment) or less severe depletion for 3 weeks have no effect on the gene expression of the transporters. Taken together, the present data demonstrate that the NET gene expression is enhanced in case of severe serotonin depletion.
我们和其他研究人员之前已经表明，严重的血清素耗竭会导致血清素转运体（5HTT）基因表达的代偿性下调。我们现在研究了5HTT和去甲肾上腺素转运体（NET）基因的表达，以评估去甲肾上腺素能和血清素能神经递质系统之间可能存在的相互作用。对氯苯丙氨酸（PCPA）处理诱导的急性严重血清素耗竭会导致NET（长型）mRNA水平升高，5HTT mRNA水平降低。转运体mRNA表达的这种变化与蛋白质表达的非显著性变化平行。慢性严重血清素耗竭联合抗抑郁药丙咪嗪治疗会导致NET（长型）mRNA水平升高。单胺氧化酶A抑制剂氯吉兰的急性治疗、急性中度去甲肾上腺素减少（α-甲基-对-酪氨酸治疗）或3周的轻度耗竭对转运体的基因表达没有影响。综上所述，目前的数据表明，在严重血清素耗竭的情况下，NET基因表达会增强。
