Effect of advanced maternal age on development of hippocampal neural stem cells in offspring rats
YANG Jing, HAN Wei, LIU Jie, YANG Chen, ZHAO Wen-Jie, SUN Hong, PAN Ya-Nan, CHEN Heng-Sheng, CHENG Li, JIANG Li
Department of Neurology, Children's Hospital of Chongqing Medical University/Ministry of Education Key Laboratory of Child Development and Disorders/National Clinical Research Center for Child Health and Disorders/China International Science and Technology Cooperation Base of Child Development and Critical Disorders/Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing 400014, China
Abstract:Objective To study the effect of advanced maternal age (AMA) on the development of hippocampal neural stem cells in offspring rats. Methods Ten 3-month-old and ten 12-month-old female Sprague-Dawley rats were housed individually with 3-month-old male rats (1:1, n=20), whose offspring rats were assigned to a control group and an AMA group. A total of 40 rats were randomly selected from each group. Immunofluorescence assay and Western blot were used to localize and determine the levels of protein expression of Nestin and doublecortin (DCX) on day 7 as well as neuronal nuclear antigen (NeuN) and glial fibrillary acidic protein (GFAP) on day 28 (n=8 for each marker). Immunofluorescence assay was also used to localize the hippocampal expression of polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) on day 14 (n=8 for each marker). Results According to the Western blot results, the AMA group had significantly lower protein expression of DCX than the control group (P < 0.05), while there were no significant differences in the protein expression of Nestin, NeuN, and GFAP between the two groups (P > 0.05). According to the results of immunofluorescence assay, the AMA group had significantly lower protein expression of Nestin, DCX, and PSA-NCAM in the hippocampal dentate gyrus (DG) region than the control group (P < 0.05), while there were no significant differences in the above indices in the hippocampal CA1 and CA3 regions between the two groups (P > 0.05). The AMA group had significantly higher expression of NeuN in the hippocampal CA1 region than the control group (P < 0.01), while there were no significant differences in the expression of NeuN in the hippocampal DG and CA3 regions between the two groups (P > 0.05). The AMA group had significantly lower expression of GFAP in the hippocampal CA1, CA3, and DG regions than the control group (P < 0.05). Conclusions AMA may cause inhibition of proliferation, survival, and migration of hippocampal neural stem cells. AMA may also affect their differentiation into neurons and astrocytes, which will eventually lead to developmental disorders of hippocampal neural stem cells in offspring rats.
YANG Jing,HAN Wei,LIU Jie et al. Effect of advanced maternal age on development of hippocampal neural stem cells in offspring rats[J]. CJCP, 2020, 22(9): 1017-1026.
Dietl A, Farthmann J. Gestational hypertension and advanced maternal age[J]. Lancet, 2015, 386(10004):1627-1628.
[2]
Han W, Dong X, Song X, et al. Effects of advanced maternal age on cognitive and emotional development in offspring rats[J]. Behav Brain Res, 2018, 353:218-226.
[3]
Gonçalves JT, Schafer ST, Gage FH. Adult neurogenesis in the hippocampus:from stem cells to behavior[J]. Cell, 2016, 167(4):897-914.
[4]
Huang H, Liu CM, Sun J, et al. Ketamine affects the neurogenesis of the hippocampal dentate gyrus in 7-Day-Old rats[J]. Neurotox Res, 2016, 30(2):185-198.
[5]
Kempermann G, Jessberger S, Steiner B, et al. Milestones of neuronal development in the adult hippocampus[J]. Trends Neurosci, 2004, 27(8):447-452.
[6]
Paredes MF, James D, Gil-Perotin S, et al. Extensive migration of young neurons into the infant human frontal lobe[J]. Science, 2016, 354(6308):aaf7073.
[7]
Martin JA, Hamilton BE, Sutton PD, et al. Births:final data for 2004[J]. Natl Vital Stat Rep, 2006, 55(1):1-101.
[8]
Wu S, Wu F, Ding Y, et al. Advanced parental age and autism risk in children:a systematic review and meta-analysis[J]. Acta Psychiatr Scand, 2017, 135(1):29-41.
[9]
Menezes PR, Lewis G, Rasmussen F, et al. Paternal and maternal ages at conception and risk of bipolar affective disorder in their offspring[J]. Psychol Med, 2010, 40(3):477-485.
[10]
Luna VM, Anacker C, Burghardt NS, et al. Adult-born hippocampal neurons bidirectionally modulate entorhinal inputs into the dentate gyrus[J]. Science, 2019, 364(6440):578-583.
[11]
Xue XJ, Yuan XB. Nestin is essential for mitogen-stimulated proliferation of neural progenitor cells[J]. Mol Cell Neurosci, 2010, 45(1):26-36.
[12]
Hill JD, Zuluaga-Ramirez V, Gajghate S, et al. Activation of GPR55 induces neuroprotection of hippocampal neurogenesis and immune responses of neural stem cells following chronic, systemic inflammation[J]. Brain Behav Immun, 2019, 76:165-181.
[13]
Tchieu J, Calder EL, Guttikonda SR, et al. NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells[J]. Nat Biotechnol, 2019, 37(3):267-275.
Ben Haim L, Rowitch DH. Functional diversity of astrocytes in neural circuit regulation[J]. Nat Rev Neurosci, 2017, 18(1):31-41.
[16]
Zott B, Busche MA, Sperling RA, et al. What happens with the circuit in Alzheimer's disease in mice and humans?[J]. Annu Rev Neurosci, 2018, 41:277-297.
[17]
Talbot ZN, Sparks FT, Dvorak D, et al. Normal CA1 place fields but discoordinated network discharge in a fmr1-null mouse model of fragile X syndrome[J]. Neuron, 2018, 97(3):684-697.e4.
[18]
Neniskyte U, Gross CT. Errant gardeners:glial-cell-dependent synaptic pruning and neurodevelopmental disorders[J]. Nat Rev Neurosci, 2017, 18(11):658-670.
[19]
Cardozo PL, de Lima IBQ, Maciel EMA, et al. Synaptic elimination in neurological disorders[J]. Curr Neuropharmacol, 2019, 17(11):1071-1095.
[20]
Chung WS, Clarke LE, Wang GX, et al. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways[J]. Nature, 2013, 504(7480):394-400.