ATP6AP2 over-expression causes morphological alterations in the hippocampus and in hippocampus-related behaviour
ATP6AP2 over-expression causes morphological alterations in the hippocampus and in hippocampus-related behaviour
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DOI：
10.1007/s00429-018-1633-1
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发表时间：
2018-06-01
影响因子：
3.1
通讯作者：
Halbach, O. Von Bohlen Und
中科院分区：
文献类型：
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作者：
Bracke, A.;Schaefer, S.;Halbach, O. Von Bohlen Und
（pro）肾素受体[(P)RR]，也称为ATP6AP2 [ATPase 6辅助蛋白2]，在大脑中高度表达。ATP6AP2在早期大脑发育、成人海马神经发生和认知功能中发挥作用。缺乏ATP6AP2具有有害影响，人类中ATP6AP2突变与x连锁智力残疾有关。然而，对于成人大脑中ATP6AP2过表达的影响知之甚少。我们假设大脑中过表达ATP6AP2的小鼠可能表现出神经解剖特征和行为反应的改变。为此，我们研究了杂合转基因雌性小鼠，证实了大脑中ATP6AP2水平的增加。我们的数据显示，ATP6AP2的过表达不会影响成年海马神经发生、运动诱导的细胞增殖或海马树突棘密度。仅在大体形态学水平上发现心室体积减小。然而，ATP6AP2过表达小鼠在孔板和新物体识别测试中表现出改变的探索行为。此外，过表达ATP6AP2的成体海马神经干细胞表现出更快的细胞周期进展和细胞增殖增加。总之，与已知的ATP6AP2缺失的有害影响相反，适度的过表达导致适度的行为改变，并影响体外细胞增殖率。
The (pro)renin receptor [(P)RR], also known as ATP6AP2 [ATPase 6 accessory protein 2], is highly expressed in the brain. ATP6AP2 plays a role in early brain development, adult hippocampal neurogenesis and in cognitive functions. Lack of ATP6AP2 has deleterious effects, and mutations of ATP6AP2 in humans are associated with, e.g. X-linked intellectual disability. However, little is known about the effects of over-expression of ATP6AP2 in the adult brain. We hypothesized that mice over-expressing ATP6AP2 in the brain might exhibit altered neuroanatomical features and behavioural responses. To this end, we investigated heterozygous transgenic female mice and confirmed increased levels of ATP6AP2 in the brain. Our data show that over-expression of ATP6AP2 does not affect adult hippocampal neurogenesis, exercise-induced cell proliferation, or dendritic spine densities in the hippocampus. Only a reduced ventricular volume on the gross morphological level was found. However, ATP6AP2 over-expressing mice displayed altered exploratory behaviour with respect to the hole-board and novel object recognition tests. Moreover, primary adult hippocampal neural stem cells over-expressing ATP6AP2 exhibit a faster cell cycle progression and increased cell proliferation. Together, in contrast to the known deleterious effects of ATP6AP2 depletion, a moderate over-expression results in moderate behavioural changes and affects cell proliferation rate in vitro.