Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats
Zhu-Jin Song
San-Juan Yang
Lan Han
Bin Wang
Guoqi Zhu
摘要：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 phosphor-ylation levels of Akt, mTOR and CREB were reduced in the hippocampus. ThThese 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.
机标关键词：
分类号：R453(治疗学)R363(病理学)R741(神经病学)
资助基金：This study was supported by the National Natural Sci-ence Foundation of China, (No. 81601181, 81673716)the Natural Science Foundation of Anhui Province of China, (No. 1808085J15)the Natural Science Research Project of Anhui Province of China, (No. KJ2016A417 (to GZ). The funding bodies played no role in the study design, in the collection, analysis and interpretation of data, in the writing of the paper, and in the decision to submit the paper for publication)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 834-840 )
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