RT Journal Article
SR Electronic
T1 Homer1 Mediates Acute Stress-Induced Cognitive Deficits in the Dorsal Hippocampus
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3857
OP 3864
DO 10.1523/JNEUROSCI.4333-12.2013
VO 33
IS 9
A1 Wagner, Klaus V.
A1 Hartmann, Jakob
A1 Mangold, Katharina
A1 Wang, Xiao-Dong
A1 Labermaier, Christiana
A1 Liebl, Claudia
A1 Wolf, Miriam
A1 Gassen, Nils C.
A1 Holsboer, Florian
A1 Rein, Theo
A1 Müller, Marianne B.
A1 Schmidt, Mathias V.
YR 2013
UL http://www.jneurosci.org/content/33/9/3857.abstract
AB In recent years, the glutamatergic system has been implicated in the development and treatment of psychiatric disorders. Glutamate signaling is processed by different receptors, including metabotropic glutamate receptors (mGluRs), which in turn interact with the scaffolding protein Homer1 to modulate downstream Ca2+ signaling. Stress is a major risk factor for the incidence of psychiatric diseases, yet acute stress episodes may have diverging effects on individuals. Cognitive impairments have often been shown to occur after episodes of stress, however the specific role of mGluR5/Homer1 signaling in the interaction of stress and cognition has not yet been elucidated. In this study we show that a single episode of social defeat stress is sufficient to specifically induce cognitive impairments in mice 8 h after the stressor without affecting the animals' locomotion or anxiety levels. We also demonstrate that Homer1b/c levels as well as mGluR5/Homer1b/c interactions in the dorsal hippocampus are reduced up to 8 h after stress. Blockade of mGluR5 during the occurrence of social stress was able to rescue the cognitive impairments. In addition, a specific overexpression of Homer1b/c in the dorsal hippocampus also reversed the behavioral phenotype, indicating that both mGluR5 and Homer1b/c play a crucial role in the mediation of the stress effects. In summary, we could demonstrate that stress induces a cognitive deficit that is likely mediated by mGluR5/Homer1 signaling in the hippocampus. These findings help to reveal the underlying effects of cognitive impairments in patients suffering from stress-related psychiatric disorders.