Decreased expression of ErbB4 and tyrosine hydroxylase mRNA and protein in the ventral midbrain of aged rats.
Decreased expression of ErbB4 and tyrosine hydroxylase mRNA and protein in the ventral midbrain of aged rats.
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DOI：
10.1016/j.neuroscience.2009.06.008
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发表时间：
2009-09-29
期刊：
影响因子：
3.3
通讯作者：
Seroogy, K. B.
中科院分区：
文献类型：
--
作者：
Dickerson, J. W.;Hemmerle, A. M.;Numan, S.;Lundgren, K. H.;Seroogy, K. B.
神经营养因子的可用性或有效性降低可能是中脑多巴胺能细胞对年龄相关变性的易感性增加的基础。神经调节蛋白（NRGs）是多种细胞类型的多营养生长因子，包括培养和体内的中脑多巴胺细胞。几乎所有中脑多巴胺神经元都表达功能性NRG受体ErbB4。为了确定在衰老过程中多巴胺能腹侧中脑NRG受体的水平是否维持，我们检测了年轻（3个月）、中年（18个月）和老年（24-25个月）布朗挪威/费舍尔344 F1大鼠ErbB4 mRNA和蛋白的表达。与年轻大鼠相比，中老年大鼠黑质致密部（SNpc）的ErbB4 mRNA水平显著降低，而邻近的腹侧被盖区（VTA）和黑质外侧部（SNl）的ErbB4 mRNA水平则没有显著降低。老龄大鼠中脑腹侧ErbB4蛋白表达明显低于年轻大鼠。与年轻动物相比，SNpc中老龄大鼠的酪氨酸羟化酶（TH） mRNA表达水平显著降低，而VTA和SNl中则没有。与幼龄动物相比，老年动物腹侧中脑酪氨酸羟化酶蛋白水平也有所下降。这些数据表明，ErbB4表达的进行性下降，与老年大鼠中脑腹侧多巴胺合成酶TH的丧失相一致，特别是在SNpc中。这些发现可能暗示NRG/ErbB4营养支持减少在多巴胺相关的衰老神经退行性疾病（如帕金森病）中的作用。
Decreased availability or efficacy of neurotrophic factors may underlie an increased susceptibility of mesencephalic dopaminergic cells to age-related degeneration. Neuregulins (NRGs) are pleotrophic growth factors for many cell types including mesencephalic dopamine cells in culture and in vivo. The functional NRG receptor ErbB4 is expressed by virtually all midbrain dopamine neurons. To determine if levels of the NRG receptor are maintained during aging in the dopaminergic ventral mesencephalon, expression of ErbB4 mRNA and protein was examined in young (3 months), middle-aged (18 months), and old (24–25 months) Brown Norway/Fischer 344 F1 rats. ErbB4 mRNA levels in the substantia nigra pars compacta (SNpc), but not the adjacent ventral tegmental area (VTA) or subtantia nigra pars lateralis (SNl), were significantly reduced in the middle-aged and old animals when compared to young rats. Protein expression of ErbB4 in the ventral midbrain was significantly decreased in the old rats when compared to the young rats. Expression of tyrosine hydroxylase (TH) mRNA levels were significantly reduced in the old rats when compared to young animals in the SNpc, but not in the VTA or SNl. Tyrosine hydroxylase protein levels in the ventral midbrain were also decreased in the old animals when compared to the young animals. These data demonstrate a progressive decline of ErbB4 expression, coinciding with a loss of the dopamine-synthesizing enzyme TH, in the ventral midbrain of aged rats, particularly in the SNpc. These findings may implicate a role for diminished NRG/ErbB4 trophic support in dopamine-related neurodegenerative disorders of aging such as Parkinson’s disease.
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影响因子：
64.8
作者：
GASSMANN, M;CASAGRANDA, F;LEMKE, G
通讯作者：
LEMKE, G
影响因子：
3.1
作者：
Di Segni, Ayelet;Farin, Keren;Pinkas-Kramarski, Ronit
通讯作者：
Pinkas-Kramarski, Ronit
影响因子：
2.9
作者：
Fox, CM;Gash, DM;Cass, WA
通讯作者：
Cass, WA
影响因子：
3.8
作者：
EMERICH, DF;MCDERMOTT, P;SANBERG, PR
通讯作者：
SANBERG, PR
影响因子：
2.9
作者：
Croll, SD;Ip, NY;Wiegand, SJ
通讯作者：
Wiegand, SJ