TY - JOUR
T1 - Beta amyloid-induced time-dependent learning and memory impairment
T2 - involvement of HPA axis dysfunction
AU - Lv, Jinpeng
AU - Chen, Ling
AU - Zhu, Naping
AU - Sun, Yindi
AU - Pan, Jianchun
AU - Gao, Jinsheng
AU - Liu, Jianwu
AU - Liu, Guangjun
AU - Tao, Yuanxiang
N1 - Publisher Copyright: © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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. Aβ1–42-treated 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, Aβ1–42-treated 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 Aβ1–42-treated 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.
AB - 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. Aβ1–42-treated 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, Aβ1–42-treated 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 Aβ1–42-treated 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.
KW - BDNF
KW - Beta amyloid 1–42
KW - CREB
KW - HPA axis
KW - Learning and memory
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UR - http://www.scopus.com/inward/citedby.url?scp=85089985759&partnerID=8YFLogxK
U2 - 10.1007/s11011-020-00613-3
DO - 10.1007/s11011-020-00613-3
M3 - Article
C2 - 32860609
SN - 0885-7490
VL - 35
SP - 1385
EP - 1394
JO - Metabolic Brain Disease
JF - Metabolic Brain Disease
IS - 8
ER -