[Effect of advanced maternal age on development of hippocampal neural stem cells in offspring rats]
1Department 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. ljiang@hospital.cqmu.edu.cn.
Insights
Advanced maternal age (AMA) in rats significantly impacts offspring hippocampal neural stem cell development, showing reduced proliferation and migration. These changes may lead to developmental disorders in the offspring.
Area of Science:
- Neuroscience
- Developmental Biology
- Reproductive Science
Background:
- Advanced maternal age (AMA) is associated with potential adverse outcomes in offspring.
- Neural stem cells in the hippocampus play a crucial role in cognitive functions.
- Understanding the impact of AMA on early neural development is critical.
Purpose of the Study:
- To investigate the effects of advanced maternal age on the development of hippocampal neural stem cells in offspring rats.
- To analyze the expression of key neural stem cell markers in relation to maternal age.
Main Methods:
- Female Sprague-Dawley rats of different ages (3 and 12 months) were used to establish control and advanced maternal age groups.
- Offspring rats were assessed using immunofluorescence and Western blot assays.
- Key markers including Nestin, doublecortin (DCX), neuronal nuclear antigen (NeuN), glial fibrillary acidic protein (GFAP), and PSA-NCAM were quantified.
Main Results:
- Advanced maternal age group showed significantly lower protein expression of DCX and PSA-NCAM in the hippocampal dentate gyrus.
- Nestin expression was also significantly lower in the dentate gyrus of the AMA group.
- While NeuN expression was higher in the CA1 region, GFAP expression was lower across hippocampal regions in the AMA group.
Conclusions:
- Advanced maternal age may inhibit the proliferation, survival, and migration of hippocampal neural stem cells in offspring.
- AMA could also affect the differentiation of these cells into neurons and astrocytes.
- These alterations suggest potential developmental disorders of hippocampal neural stem cells in offspring from older mothers.
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.
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