Article Figures & Data
Figures
- Figure 1.
Neuroendocrine and behavioral effects of a single defeat session. A, Defeated mice show significantly increased corticosterone levels up to 8 h after onset of the stressor. B, In the spatial object recognition test, animals did not discriminate between the displaced and the nondisplaced object when stressed 8 h before. C, In the Y-maze, we found the same memory impairment as when animals were defeated 8 h before. D, Both control and defeated mice spent equal time sniffing in the female urine sniffing test 8 h after the defeat, indicating that there is no anhedonic behavior induced by a single defeat session. E, In the elevated plus maze, defeated animals show the same anxiety-related phenotype as their control littermates when tested 8 h after the stress. *p < 0.05; data are expressed as mean ± SEM.
- Figure 2.
Homer1 mRNA level alterations in response to stress. A, After 4 and 8 h, Homer1b/c mRNA levels in the CA1 region are reduced. This reduction normalizes after 24 h. B, Representative autoradiographs of Homer1b/c mRNA levels in the hippocampus. C, Homer1a levels are not significantly altered in response to a single social defeat. One hour after onset of the stressor, an increase in Hoemr1a mRNA failed to reach significance (p = 0.077). D, Representative autoradiographs of Homer1a mRNA levels in the hippocampus. E, Interactions of mGluR5 and Homer1b/c are decreased 8 h after defeat stress. F, Representative Western blot of the mGluR5/Homer1 immunoprecipitation. For the technical control, a pooled lysate was incubated without primary antibodies. *p < 0.05, data are expressed as mean ± SEM.
- Figure 3.
Manipulation of mGluR5/Homer1 but not glucocorticoid receptor signaling rescues cognitive impairments. A, A single injection of DEX (dexamethasone) that mimics a corticosterone response to a stressor was not able to induce changes in Homer1b/c mRNA levels. B, Eight hours after a single injection of DEX, experimental mice are not impaired in the Y-maze memory performance task. C, Mice that received a RU486 injection before the stressor are still affected by the defeat stress and cannot discriminate between the displaced and the nondisplaced object. D, Mice that received a MTEP injection before the stressor show functional learning behavior independent of the condition. *p < 0.05, data are expressed as mean ± SEM.
- Figure 4.
Overexpression of Homer1b/c in the dorsal hippocampus rescues memory impairments induced by defeat stress. A, Homer1b/c mRNA levels in the dorsal hippocampus. Infection with the viral construct induced a robust increase. B, Representative autoradiographs of Homer1b/c mRNA levels in the dorsal and ventral hippocampus of control and Homer1 OE animals. C, Schematic representation of the extent of viral infection in the hippocampus from −1.44 to −2.72 mm posterior to bregma. Dark green, Strongest overexpression; light green, weaker overexpression. D, Visualization of Homer1b/c expression in the hippocampal DG region 5 weeks after injection of control (top panels) or Homer1b/c-expressing virus (bottom panels) (scale, 200 μm). E, Overexpression of Homer1b/c in the dorsal hippocampus prevents learning deficits induced by acute defeat stress. *p < 0.05, data are expressed as mean ± SEM.
