Reduced Proliferation in the Adult Mouse Subventricular Zone Increases Survival of Olfactory Bulb Interneurons

被引:32
作者
Sui, Yi [1 ,2 ]
Horne, Malcolm K. [1 ,2 ,3 ]
Stanic, Davor [1 ,2 ]
机构
[1] Univ Melbourne, Neurodegenerat Div, Florey Neurosci Inst, Parkville, Vic 3052, Australia
[2] Univ Melbourne, Ctr Neurosci, Parkville, Vic 3052, Australia
[3] St Vincents Hosp, Dept Neurol, Fitzroy, Vic 3065, Australia
来源
PLOS ONE | 2012年 / 7卷 / 02期
基金
英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词
EXTERNAL PLEXIFORM LAYER; MICROTUBULE-ASSOCIATED PROTEIN; PRECURSOR CELL-PROLIFERATION; NEWLY GENERATED NEURONS; CENTRAL-NERVOUS-SYSTEM; NEWBORN NEURONS; MAMMALIAN BRAIN; RAT-BRAIN; TYROSINE-HYDROXYLASE; SENSORY EXPERIENCE;
D O I
10.1371/journal.pone.0031549
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Neurogenesis in the adult brain is largely restricted to the subependymal zone (SVZ) of the lateral ventricle, olfactory bulb (OB) and the dentate subgranular zone, and survival of adult-born cells in the OB is influenced by factors including sensory experience. We examined, in mice, whether survival of adult-born cells is also regulated by the rate of precursor proliferation in the SVZ. Precursor proliferation was decreased by depleting the SVZ of dopamine after lesioning dopamine neurons in the substantia nigra compacta with 6-hydroxydopamine. Subsequently, we examined the effect of reduced SVZ proliferation on the generation, migration and survival of neuroblasts and mature adult-born cells in the SVZ, rostral migratory stream (RMS) and OB. Proliferating cells in the SVZ, measured by 5-bromo-2-deoxyuridine (BrdU) injected 2 hours prior to death or by immunoreactivity against Ki67, were reduced by 47% or 36%, respectively, 7 days after dopamine depletion, and by 29% or 31% 42 days after dopamine depletion, compared to sham-treated animals. Neuroblast generation in the SVZ and their migration along the RMS were not affected, neither 7 nor 42 days after the 6-hydroxydopamine injection, since the number of doublecortin-immunoreactive neuroblasts in the SVZ and RMS, as well as the number of neuronal nuclei-immunoreactive cells in the OB, were stable compared to control. However, survival analysis 15 days after 6-hydroxydopamine and 6 days after BrdU injections showed that the number of BrdU+ cells in the SVZ was 70% higher. Also, 42 days after 6-hydroxydopamine and 30 days after BrdU injections, we found an 82% increase in co-labeled BrdU+/gamma-aminobutyric acid-immunoreactive cell bodies in the granular cell layer, while double-labeled BrdU+/tyrosine hydroxylase-immunoreactive cell bodies in the glomerular layer increased by 148%. We conclude that the number of OB interneurons following reduced SVZ proliferation is maintained through an increased survival of adult-born precursor cells, neuroblasts and interneurons.
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页数:14
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