Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats
Our previous studies showed that the early use of calpain inhibitors reduces calpain activity in multiple brain regions, and that postnatal treatment with calpeptin may lead to cerebellar motor dysfunction. However, it remains unclear whether postnatal calpeptin application affects hippocampus-relat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2019-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=5;spage=834;epage=840;aulast=Song |
| _version_ | 1818264601354043392 |
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| author | Zhu-Jin Song San-Juan Yang Lan Han Bin Wang Guoqi Zhu |
| author_facet | Zhu-Jin Song San-Juan Yang Lan Han Bin Wang Guoqi Zhu |
| author_sort | Zhu-Jin Song |
| collection | DOAJ |
| description | Our previous studies showed that the early use of calpain inhibitors reduces calpain activity in multiple brain regions, and that postnatal treatment with calpeptin may lead to cerebellar motor dysfunction. However, it remains unclear whether postnatal calpeptin application affects hippocampus-related behaviors. In this study, Sprague-Dawley rats were purchased from the Animal Center of Anhui Medical University of China. For the experiments in the adult stage, rats were intraperitoneally injected with calpeptin, 2 mg/kg, once a day, on postnatal days 7–14. Then on postnatal day 60, the Morris water maze test was used to evaluate spatial learning and memory abilities. The open field test was carried out to assess anxiety-like activities. Phalloidin staining was performed to observe synaptic morphology in the hippocampus. Immunohistochemistry was used to count the number of NeuN-positive cells in the hippocampal CA1 region. DiI was applied to label dendritic spines. Calpeptin administration impaired spatial memory, caused anxiety-like behavior in adulthood, reduced the number and area of apical dendritic spines, and decreased actin polymerization in the hippocampus, but did not affect the number of NeuN-positive cells in the hippocampal CA1 region. For the neonatal experiments, neonatal rats were intraperitoneally injected with calpeptin, 2 mg/kg, on postnatal days 7 and 8. Western blot assay was performed to analyze the protein levels of Akt, Erk, p-Akt, p-Erk1/2, Erk1/2, SCOP, PTEN, mTOR, p-mTOR, CREB and p-CREB in the hippocampus. SCOP expression was increased, and the phosphorylation levels of Akt, mTOR and CREB were reduced in the hippocampus. These findings show that calpeptin administration after birth affects synaptic development in neonatal rats by inhibiting the Akt/mTOR signaling pathway, thereby perturbing hippocampal function. Therefore, calpeptin administration after birth is a risk factor for neurodevelopmental defects. |
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| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-12T19:37:30Z |
| publishDate | 2019-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
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| series | Neural Regeneration Research |
| spelling | doaj.art-76db8fe139854673868391a68a0849702022-12-22T00:14:16ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742019-01-0114583484010.4103/1673-5374.249231Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal ratsZhu-Jin SongSan-Juan YangLan HanBin WangGuoqi ZhuOur previous studies showed that the early use of calpain inhibitors reduces calpain activity in multiple brain regions, and that postnatal treatment with calpeptin may lead to cerebellar motor dysfunction. However, it remains unclear whether postnatal calpeptin application affects hippocampus-related behaviors. In this study, Sprague-Dawley rats were purchased from the Animal Center of Anhui Medical University of China. For the experiments in the adult stage, rats were intraperitoneally injected with calpeptin, 2 mg/kg, once a day, on postnatal days 7–14. Then on postnatal day 60, the Morris water maze test was used to evaluate spatial learning and memory abilities. The open field test was carried out to assess anxiety-like activities. Phalloidin staining was performed to observe synaptic morphology in the hippocampus. Immunohistochemistry was used to count the number of NeuN-positive cells in the hippocampal CA1 region. DiI was applied to label dendritic spines. Calpeptin administration impaired spatial memory, caused anxiety-like behavior in adulthood, reduced the number and area of apical dendritic spines, and decreased actin polymerization in the hippocampus, but did not affect the number of NeuN-positive cells in the hippocampal CA1 region. For the neonatal experiments, neonatal rats were intraperitoneally injected with calpeptin, 2 mg/kg, on postnatal days 7 and 8. Western blot assay was performed to analyze the protein levels of Akt, Erk, p-Akt, p-Erk1/2, Erk1/2, SCOP, PTEN, mTOR, p-mTOR, CREB and p-CREB in the hippocampus. SCOP expression was increased, and the phosphorylation levels of Akt, mTOR and CREB were reduced in the hippocampus. These findings show that calpeptin administration after birth affects synaptic development in neonatal rats by inhibiting the Akt/mTOR signaling pathway, thereby perturbing hippocampal function. Therefore, calpeptin administration after birth is a risk factor for neurodevelopmental defects.http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=5;spage=834;epage=840;aulast=Songnerve regeneration; postnatal; calpeptin; learning and memory; hippocampus; spine development; SCOP; AKT; mTOR; neural regeneration |
| spellingShingle | Zhu-Jin Song San-Juan Yang Lan Han Bin Wang Guoqi Zhu Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats Neural Regeneration Research nerve regeneration; postnatal; calpeptin; learning and memory; hippocampus; spine development; SCOP; AKT; mTOR; neural regeneration |
| title | Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats |
| title_full | Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats |
| title_fullStr | Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats |
| title_full_unstemmed | Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats |
| title_short | Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats |
| title_sort | postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats |
| topic | nerve regeneration; postnatal; calpeptin; learning and memory; hippocampus; spine development; SCOP; AKT; mTOR; neural regeneration |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=5;spage=834;epage=840;aulast=Song |
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