Altered emotionality, hippocampus-dependent performance and expression of NMDA receptor subunit mRNAs in chronically stressed mice

Abstract

N-Methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission in the hippocampus is implicated in cognitive and emotional disturbances during stress-related disorders. Here, using quantitative RT-PCR, we investigated the hippocampal expression of NR2A, NR2B and NR1 subunit mRNAs in a mouse stress paradigm that mimics clinically relevant conditions of simultaneously affected emotionality and hippocampus-dependent functions. A 2-week stress procedure, which comprised ethologically valid stressors, exposure to a rat and social defeat, was applied to male C57BL/6J mice. For predation stress, mice were introduced into transparent containers that were placed in a rat home cage during the night; social defeat was applied during the daytime using aggressive CD1 mice. This treatment impaired hippocampusdependent performance during contextual fear conditioning. A correlation between this behavior and food displacement performance was demonstrated, suggesting that burrowing behavior is affected by the stress procedure and is hippocampus-dependent. Stressed mice (n ¼ 22) showed behavioral invigoration and anomalous anxiolytic-like profiles in the O-maze and brightly illuminated open field, unaltered short-term memory in the step-down avoidance task and enhanced aggressive traits, as compared to non-stressed mice (n ¼ 10). Stressed mice showed increased basal serum corticosterone concentrations, hippocampal mRNA expression for the NR2A subunit of the NMDAR and in the NR2A/NR2B ratio; mRNA expression of NR2B and NR1 was unchanged. Thus, stress-induced aberrations in both hippocampal-dependent performance and emotional abnormalities are associated with alterations in hippocampal mRNA NR2A levels and the NR2A/NR2B ratio and not with mRNA expression of NR2B or NR1.

Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression

“…For acute predation stress, mice were introduced into specialized cylindrical containers allowing visual and odor contact (Costa-Nunes et al, 2014), which were placed into the rat home cage. Visual scoring of digitized EEG and EMG traces (EEG filtering 0.5–49.9 Hz and EMG filtering 15–49.9 Hz) was performed over 10 s bins to quantify the number and duration of sleep-wake episodes and the circadian scheduling of sleep-wake states as described elsewhere (Cespuglio et al, 2012; Strekalova et al, 2015).…”

“…The apparatus was placed on a dark surface in order to reduce reflection and maintain control over lighting conditions during testing. Anxiety-like behavior was assessed using previously validated parameters that were scored manually as described elsewhere (Strekalova and Steinbusch, 2010; Costa-Nunes et al, 2014; Cline et al, 2015). Mice were placed in one of the closed-arm compartments of the apparatus.…”

“…In the first experiment, using a model of stress-induced anhedonia (Strekalova and Steinbusch, 2010; Costa-Nunes et al, 2014; Cline et al, 2015) we investigated whether a pre-treatment in C57BL6J mice with DS, at the dose of 25 mg/kg/day intraperitoneally for 7 days, would improve normal sleep rebound (augmentation) following acute stress, a sign of adaptive stress response (Marinesco et al, 1999; Suchecki et al, 2012; Albu et al, 2014; Keshavarzy et al, 2014), as well as contextual fear conditioning learning that is regarded to be related to the adaptive sleep function (Rolls et al, 2013; Barnes and Wilson, 2014). Also, we studied hippocampal gene expression of NMDA receptor subunit NR2A and the ratio of NR2A/NR2B, whose increases were previously demonstrated to accompany a development of stress-induced anhedonia in the here applied chronic stress model (Costa-Nunes et al, 2014).…”

“…Also, we studied hippocampal gene expression of NMDA receptor subunit NR2A and the ratio of NR2A/NR2B, whose increases were previously demonstrated to accompany a development of stress-induced anhedonia in the here applied chronic stress model (Costa-Nunes et al, 2014). Notably, changes in the NMDA-receptor mediated transmission were shown to underlie the antidepressant effects of the neuronal insulin sensitizer pioglitazone (Salehi-Sadaghiani et al, 2012).…”

Algorithm for the diagnosis, treatment, and prevention of stress (for general practitioners)

“…Она отража-ет дезадаптацию на клеточном уровне. Поэтому встречается не только при стрессе, но и при различных патологических состоя-ниях, например, при окислительном стрессе, дефиците магния, гипергомоцистеинемии, а также позволяет объяснить коморбид-ность неврологических заболеваний и аффективных расстройств (например, депрессии) [18,19].…”