Beta amyloid-induced time-dependent learning and memory impairment: involvement of HPA axis dysfunction
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ORIGINAL ARTICLE
Beta amyloid-induced time-dependent learning and memory impairment: involvement of HPA axis dysfunction Jinpeng Lv 1 & Ling Chen 2 & Naping Zhu 3 & Yindi Sun 4 & Jianchun Pan 3 & Jinsheng Gao 5 & Jianwu Liu 1 & Guangjun Liu 6 Yuanxiang Tao 7
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Received: 21 January 2020 / Accepted: 24 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Aβ aggregation is one of the pathological biomarkers of Alzheimer’s disease (AD). However, the possible mechanism related to Aβ-induced pathological signaling pathway is still unknown. In the present study, Aβ1–42-induced time-dependent memory impairment and its possible relationship to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity were examined. Aβ1–42treated mice significantly impaired acquisition activity in the learning curve at 10 days, 1 and 4 months in the Morris water-maze (MWM) task. This learning activity was back to normal at 8 months after Aβ1–42 treatment. In the probe trial test, Aβ1–42treated mice needed longer latencies to touch the precious platform location and fewer numbers of crossing from 10 days to 4 months after microinjection. This Aβ1–42 induced memory loss was consistent with the results of the step-down passive avoidance test. The HPA axis related parameters, such as corticosterone (CORT) level in the serum, glucocorticoid receptor (GR) and corticotropin-releasing factor receptor (CRF-R) expression in the frontal cortex and hippocampus increased in Aβ1–42treated mice from 10 days to 4 months. While the downstream molecules phosphorylation of cyclic AMP response element binding (pCREB) and brain-derived neurotrophic factor (BDNF) expression decreased during this time. These effects were back to normal 8 months after treatment with Aβ1–42. Altogether, our results suggested that Aβ1–42 induced significant learning and memory impairment, which is involved in HPA axis dysfunction. Keywords Beta amyloid 1–42 . Learning and memory . HPA axis . CREB . BDNF
Jinpeng Lv, Ling Chen, Naping Zhu and Yindi Sun contributed equally to this work. Lv J, Chen L, Zhu N and Sun Y should be considered co-first authors Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11011-020-00613-3) contains supplementary material, which is available to authorized users. * Guangjun Liu [email protected]
3
Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China
* Yuanxiang Tao [email protected]
4
Department of Traditional Medical Orthopedics, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi, China
5
Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan 030000, China
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The Second People’s Hospital of Changzhou, Affiliate Hospital of NanJing Medical University, Changzhou 213000, China
7
Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA
1
College of Pharmaceutical Engineering and Life Sciences, Chan
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