We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN<sup>+</sup> cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits.
Recent evidence highlights the protective role of reelin against amyloid β (Aβ)-induced synaptic dysfunction and cognitive impairment in Alzheimer disease (AD).
These results suggest that early-life stress may mediate cognitive impairment in middle-age ApoE4-TR mice through sustained reduction of GABAergic neurons and Reelin expression, which might further diminish the activation of the Fyn/NMDAR2B signaling pathway.
The differences between the subsamples remained significant after taking into account an intragenic Reelin STR allele, previously associated with cognitive impairments and almost absent from the isolate, in addition to disorder characteristics and familial loading.
Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plasticity, leading ultimately to the cognitive deficits present in these disorders.
Reductions in Reelin protein and mRNA and Dab 1 mRNA and elevations in Reln receptor VLDLR mRNA demonstrate impairments in the Reelin signaling system in autism, accounting for some of the brain structural and cognitive deficits observed in the disorder.