Beta amyloid-induced time-dependent learning and memory impairment: involvement of HPA axis dysfunction

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.