Changes in NR2B-NMDA Receptor Expression Relate to Individual Differences in Adaptability to Food Restriction-Stress

The eating disorder Anorexia Nervosa has an extremely high mortality rate of 5.9% (Arcelus et al. 2011) and a poorly understood neurobiology. Research indicates the animal model Activity-Based Anorexia (ABA) may provide insight into the neural correlates of its behavioral and physical markers, hyperactivity and weight loss. Previously, female ABA rodents were shown to have increased levels of the NR2B subunit of NMDA receptor (NMDAR), an excitatory glutamate receptor, in stratum radiatum of dorsal hippocampal CA1. Increased NR2B-NMDAR levels may increase excitability in hippocampus, an anxiety-regulating brain region, possibly increasing anxiety-like behavior (Chen et al. 2017) such as hyperactivity (Wable et al. 2015). Here we tested whether adolescent female mice exposed to a second food restriction (ABA2) also demonstrate the behavioral and physical markers of ABA. NR2B- NMDARs in ABA2 and control mice were immunolabeled for electron microscopy and quantified at excitatory synapses of CA1 at various pre-, post-, and peri-synaptic regions. Electron microscopy was chosen to selectively observe NR2B-immunoreactivity at distinct pre- and post-synaptic compartments because NMDARs can operate differently depending on how closely they are anchored to the synaptic junction immediately apposed to presynaptic release site (Hardingham and Bading 2010). We found that ABA2 animals had more NR2B-labeling in presynaptic terminals and postsynaptic cytoplasm than controls. Increased NR2B-labeling at postsynaptic density correlated with increased running activity during food access and weight loss, suggesting that NR2B-NMDARs at postsynaptic density may mediate vulnerability to ABA2. Increased levels of NR2B-labeling at the extra-synaptic membrane of dendritic spines correlated with less running during ABA2, suggesting NR2B at this site may mediate ABA resilience. The results indicate localized NR2B expression correlates with adaptability to second exposure to food restriction and support a neurobiological basis for ABA