Fig. 10
From: Early-life stress leads to impaired spatial learning and memory in middle-aged ApoE4-TR mice
The cognitive impairment mediated by the Reelin-Fyn-NR2B signaling pathway in 12-month-old ApoE4-TR mice that underwent early-life early CUMS intervention. ApoE secreted by astrocytes and Reelin produced by GABAergic neurons compete to bind to ApoER2 in neurons. Reelin binding to ApoER2 sequentially induces the activation of Dab1, SRC family tyrosine kinases (Fyn) and NMDAR2B subunits, which in turn promote the influx of Ca2+ and expression of the cognition-associated proteins. Following early-life CUMS intervention, the number of GABAergic neurons and the level of Reelin in the prefrontal cortex and the DG of the hippocampus of the 12-month-old ApoE4-TR mice, compared with those of other groups, are reduced, thus down-regulating the activation of Fyn/p-NR2B