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Hippocampal Perineuronal Nets Are Required for the Sustained Antidepressant Effect of Ketamine

For a conclusion of this study – the current experiments demonstrate that PNNs, the specialized extracellular matrix that surrounds PV cells in the vHipp, are necessary for the sustained antidepressant response to ketamine. Disruptions in the extracellular matrix have been observed in patients with psychiatric disorders such as depression and schizophrenia (Lubbers et al., 2014). Therefore, understanding the role of PNNs in the antidepressant action of ketamine may have important implications for this novel and promising antidepressant drug.

N-methyl-D-aspartate receptor antagonists, like ketamine, produce a rapid-acting and long-lasting antidepressant effect. Although the mechanism is not completely understood, ketamine is thought to preferentially target N-methylD-aspartate receptors on fast-spiking parvalbumin-containing interneurons. The function of parvalbumin-containing interneurons is dependent on perineuronal nets, a specialized form of the extracellular matrix that surrounds these cells.

Summary: Ketamine affects perinuclear networks of cells around the hippocampal cells. These cells are inhibitory to the main neuron cells and are shut down by Ketamine, thus activating dormant pathways in a depressed mind.

Hippocampal Perineuronal Nets Are Required for the sustained antidepressant effects of Ketamine

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