MPTP Impairs Dopamine D1 Receptor-Mediated Survival of Newborn Neurons in Ventral Hippocampus to Cause Depressive-Like Behaviors in Adult Mice.
MPTP Impairs Dopamine D1 Receptor-Mediated Survival of Newborn Neurons in Ventral Hippocampus to Cause Depressive-Like Behaviors in Adult Mice.
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MPTP 损害腹侧海马新生神经元多巴胺 D1 受体介导的存活，导致成年小鼠出现抑郁样行为。
DOI：
10.3389/fnmol.2016.00101
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发表时间：
2016
影响因子：
4.8
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Zhang T;Hong J;Di T;Chen L
Parkinson’s disease (PD) is characterized by motor symptoms with depression. We evaluated the influence of dopaminergic depletion on hippocampal neurogenesis process to explore mechanisms of depression production. Five consecutive days of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection in mice (MPTP-mice) reduced dopaminergic fibers in hippocampal dentate gyrus (DG). MPTP-mice exhibited depressive-like behaviors later for 2–3 weeks. BrdU was injected 4 h after last-injection of MPTP. BrdU-positive (BrdU+) cells in dorsal (d-DG) and ventral (v-DG) DG were examined on day 1 (D1), 7 (D7), 14 (D14) and 21 (D21) after BrdU injection. Fewer D7-, D14- and D21-BrdU+ cells or BrdU+/NeuN+ cells, but not D1-BrdU+ cells, were found in v-DG of MPTP-mice than in controls. However, the number of BrdU+ cells in d-DG did not differ between the both. Loss of doublecortin-positive (DCX+) cells was observed in v-DG of MPTP-mice. Protein kinase A (PKA) and Ca2+/cAMP-response element binding protein (CREB) phosphorylation were reduced in v-DG of MPTP-mice, which were reversed by D1-like receptor (D1R) agonist SKF38393, but not D2R agonist quinpirole. The treatment of MPTP-mice with SKF38393 on days 2–7 after BrdU-injection reduced the loss of D7- and D21-BrdU+ cells in v-DG and improved the depressive-like behaviors; these changes were sensitive to PKA inhibitor H89. Moreover, the v-DG injection of SKF38393 in MPTP-mice could reduce the loss of D21-BrdU+ cells and relieve the depressive-like behaviors. In control mice, the blockade of D1R by SCH23390 caused the reduction of D21-BrdU+ cells in v-DG and the depressive-like behaviors. Our results indicate that MPTP-reduced dopaminergic depletion impairs the D1R-mediated early survival of newborn neurons in v-DG, producing depressive-like behaviors.
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影响因子：
2.7
作者：
Gorton, Lori M.;Vuckovic, Marta G.;Vertelkina, Nina;Petzinger, Giselle M.;Jakowec, Michael W.;Wood, Ruth I.
通讯作者：
Wood, Ruth I.
影响因子：
4.7
作者：
Kim Y;Wang WZ;Comte I;Pastrana E;Tran PB;Brown J;Miller RJ;Doetsch F;Molnár Z;Szele FG
通讯作者：
Szele FG
影响因子：
6.1
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Khaindrava, Vitaly;Salin, Pascal;Daszuta, Annie
通讯作者：
Daszuta, Annie
影响因子：
2.7
作者：
Lai, Yu-Ting;Fan, Hsin-Yi;Yu, Lung
通讯作者：
Yu, Lung
影响因子：
3.3
作者：
Miyamoto, N.;Tanaka, R.;Urabe, T.
通讯作者：
Urabe, T.