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Remodeling chromatin and synapses in depression

Nature Medicine volume 19, pages 267–268 (2013)Cite this article

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The long-term behavioral deficits observed in depression are associated with altered spine synapses in specific neuronal circuits. A new study shows that chromatin remodeling decreases the expression of Ras-related C2 botulinum toxin substrate 1 (Rac1) and that the deficit in this small Rho GTPase is sufficient and necessary for altered spines and behavioral abnormalities in mice after social defeat (pages 337–344).

Major depression is a widespread debilitating illness characterized by decreased mood, pleasure, motivation and reward. In addition to neurochemical imbalances, clinical and basic research has shown substantial structural abnormalities in depression-related brain regions that are associated with illness1,2,3. These changes include decreased volumes of the hippocampus and prefrontal cortex (PFC) and decreased synapse number in the postmortem PFC of subjects with depression4. Studies of chronic stress and social defeat in rodents also show decreased dendrite branching and spine synapses in the PFC and hippocampus; conversely, these rodents also show an increased number of spines in the nucleus accumbens (NAc), the primary target of the mesolimbic dopamine reward system5. However, the molecular and cellular mechanisms that contribute to the synaptic alterations in the major brain reward center have not been uncovered.

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Figure 1: Social defeat in mice leads to histone modifications that decrease Rac1 expression.

Debbie Maizels

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  1. Ronald S. Duman is in the Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, Connecticut, USA.,

    Ronald S. Duman

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  1. Ronald S. Duman
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Correspondence to Ronald S. Duman.

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Duman, R. Remodeling chromatin and synapses in depression. Nat Med 19, 267–268 (2013). https://doi.org/10.1038/nm.3125

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