Haydon Lab Discovers Role of Astrocytes in Schizophrenia

On May 4, 2017 GliaCure President Philip Haydon’s laboratory at Tufts University published its findings on the role of astrocytes in schizophrenia in the journal Neuron.

N-methyl D-aspartate receptors (NMDARs) play a direct role in many aspects of brain physiology. It is hypothesized that diminished functioning of synaptic NMDAR signaling underlies the etiology of schizophrenia. NMDARs are activated by an agonist, glutamate, and by a co-agonist, D-serine. The Haydon lab discovered that D-serine levels oscillate in mouse hippocampus as a function of wakefulness, an oscillation that influences learning performance throughout the day. The group demonstrated that D-serine release is driven by the wakefulness-dependent activity of specialized nerve transmission fibers through the α7-nicotinic acetylcholine receptor (α7nAChR). They determined that astrocytes are central to this mechanism: astrocytes locally shape synaptic properties to the ongoing brain activity by monitoring the neuromodulator environment, a new function that they term contextual guidance. Based on their findings the team concluded that astrocytes tune the gating of synaptic NMDARs to the vigilance state, a finding that is directly relevant to schizophrenia, a disorder characterized by NMDAR and low cholinergic function. They tested this finding by bypassing cholinergic activity with a clinically-tested α7nAChR agonist, EVP-6124, and found that this treatment successfully enhanced NMDAR activation. This study offers a new functional framework for the treatment of schizophrenia and opens the search for innovative approaches and targets in the field of glial biology. See the video abstract at https://www.youtube.com/watch?v=4jLyzRKAs1k.