期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2016.00101
关键词
Parkinson's disease (PD); dopaminergic receptor (DR); depression; neurogenesis; hippocampal dentate gyrus (DG)
资金
- National 973 Basic Research Program of China [2014CB943303]
- National Natural Science Foundation of China [81471157, 81671253]
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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