Abstract
The dorsal hippocampus is involved in behavioral avoidance regulation. It is unclear how experiences such as the neonatal stress of maternal deprivation (MD) and post-weaning environmental enrichment (EE) affect avoidance behavior and the dorsal hippocampal parameters, including neuronal morphology, corticotrophin-releasing hormone (CRH) signaling, and oxytocin receptor (OTR) level. In male BALB/c mice, we found that MD impaired avoidance behavior in the step-on test compared to non-MD and EE rearing conditions could alleviate that partially. MD increased neuronal branches in the CA1 but decreased synaptic connection levels in the CA2, CA3, and DG. Meanwhile, MD increased the CA1’s OTR levels, which negatively correlated with nucleus densities. MD also increased the CA1’s and CA2’s CRH levels, which positively correlated with CRHR1 levels. However, MD statistically elevated the CA3’s CRH receptor 1 (CRHR1) levels, which negatively correlated with nucleus densities and, probably, synaptic connection levels in the CA3. The additive effects of MD and EE maintained similar CRH levels and CRHR1 levels as well as OTR levels in the hippocampal areas as the additive of non-MD and non-EE. However, the presence of MD and EE still decreased the CA1’s neuronal branches and the CA2’s and DG’s synaptic connection levels. The study illustrates how MD and EE affect avoidance behaviors, hippocampal neuron morphology, and CRH and OTR levels. The results indicate that the late-life environmental improvement partially restores the alterations in dorsal hippocampal areas induced by early life stress.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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Funding
This work was supported by the National Natural Science Foundation of China [Nos. 81570725 and 81870949] to Yu-Hong Jing.
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FW was responsible for experimental design. FW performed the experiments and wrote the manuscript. XD, BM, WL, YC, and TZ assisted FW in analyzing Golgi–Cox staining. YZ, LZ (Lang Zhang), and LZ (Long Zhao) helped FW with the mouse husbandry work. LZ (Long Zhao) and YJ assisted FW with the data collection and analysis. FW and YJ were responsible for the revision.
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10571_2022_1292_MOESM4_ESM.tiff
Supplementary file4 (TIFF 1821 kb) Fig. s1 Antibodies used in the study. (a) Western blots of mouse brain tissue lysate were used to check the characterization of the antibodies. (b) oxytocin receptor (OTR). (c) Corticotrophin-releasing hormone (CRH). (d) Corticotrophin-releasing hormone receptor 1 (CRHR1). (e) Synaptophysin (SYP). (f) Postsynaptic density protein-95 (PSD95)
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Supplementary file5 (TIFF 323 kb) Fig. s2 Effects of maternal deprivation (MD) and environment enrichment (EE) on eye-opening and motion performance of male BALB/c mice. (a) Body weights on the post neonatal day (PND) 12. (b) The PND of eye-opening. (c) Body weights on the PND of eye-opening. (d) Quantification analysis of the latencies to fall off in the rotarod test. The data are presented as median with interquartile. A Student’s t-test was used in (a) and (c). A Mann-Whitney U-test was used in (b). A two-way ANOVA was used in (d). a MD vs. non-MD in the absence of EE, P < 0.05; b MD vs. non-MD in the presence of EE, P < 0.05; c EE vs. non-EE in the absence of MD, P < 0.05; d EE vs. non-EE in the presence of MD, P < 0.05
10571_2022_1292_MOESM6_ESM.tiff
Supplementary file6 (TIFF 1266 kb) Fig. s3 Effects of maternal deprivation (MD) and environment enrichment (EE) on spine subtype densities of the neuronal secondary branches in the dorsal hippocampus. (a) Schematic diagram of the studied spine subtypes. The spine subtype densities of (b) the basal branches in the CA1, (c) the apical branches in the CA1, (d) the basal branches in the CA2, (e) the apical branches in the CA2, (f) the basal branches in the CA3, (g) the apical branches in the CA3, and (h) the secondary branches in the DG. The data are presented as median with interquartile. n = 18 secondary branches from 18 neurons in each hippocampal area of 4 mice per group. A generalized estimate equation was used to analyze the data in (b–h). a MD vs. non-MD in the absence of EE, P < 0.05; b MD vs. non-MD in the presence of EE, P < 0.05; c EE vs. non-EE in the absence of MD, P < 0.05; d EE vs. non-EE in the presence of MD, P < 0.05;e non-MD + non-EE vs. MD + EE, P < 0.05
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Supplementary file7 (TIFF 3772 kb) Fig. s4 Effects of maternal deprivation (MD) and environment enrichment (EE) on the oxytocin receptor (OTR) levels in the lateral entorhinal area (ENTL). (a) Schematic diagram of the circuitry between the hippocampus and ENTL. (b) Representative images of the OTR immunochemistry in the ENTL. Scale bar = 200 µm. (c) Quantitative analysis of the total OTR protein level in the ENTL. A two-way ANOVA was used. (d) Correlation matrix analysis of the OTR levels in the areas of the ENTL. (e) Quantitative analysis of the OTR protein levels in the layers of the ENTL. A three-way ANOVA was used. The data are presented as median with interquartile. n = 5–6 mice per group. a MD vs. non-MD in the absence of EE, P < 0.05; d EE vs. non-EE in the presence of MD, P < 0.05
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Wei, F., Deng, X., Ma, B. et al. Experiences Shape Hippocampal Neuron Morphology and the Local Levels of CRHR1 and OTR. Cell Mol Neurobiol 43, 2129–2147 (2023). https://doi.org/10.1007/s10571-022-01292-7
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DOI: https://doi.org/10.1007/s10571-022-01292-7