 to increase neuron activity when needed. But after being soaked in D-serine, the plasticity of the hippocampus in brain samples improved.
A reduction in the size of the hippocampus is one of the most common findings in depressed patients and in this depressed strain of rats. It has a “prominent role” in memory and a potential role in emotional symptoms, say the authors.
Reporting the findings in the journal Molecular Psychiatry, the authors state, “Both synaptic plasticity and memory impairments were restored by administration of D-serine.”
Dr. Lindskog says, “D-serine doesn’t pass the blood-brain barrier particularly well, so it’s not really a suitable candidate on which to base a drug. But the mechanism that we’ve identified, whereby it’s possible to increase plasticity and improve memory, is a feasible route that we might be able to reach in a way that doesn’t involve D-serine.”
She believes it is crucial to learn more about this process. “These findings open up new brain targets for the development of more potent and efficient antidepressant drugs,” Dr. Lindskog says.
In their journal paper, the team explains that current antidepressant drugs sometimes resolve emotional symptoms without benefiting depression-linked deficits in memory and learning. This discrepancy “suggests the involvement of different mechanisms in the origin of these two key aspects of depression,” they write.
Perhaps this study holds the key to these different mechanisms. As the researchers say, “Based on our results, we propose a mechanism in which dysfunctional astrocytic regulation of glutamate affects glutamatergic transmission, causing memory deficits that can be restored independently of the emotional aspects of depression.”
They can also account for the lower D-serine level in the hippocampus of depressed rats: it is due to changes in the shape and function of astrocyte neurons.
“In summary,” they write, “our data describe interactions within the glutamatergic system that should be considered when designing new therapies for depression.” Several different aspects of the system should be targeted “to effectively treat both the cognitive and emotional symptoms that are associated with depression,” they add.
More recently it has been confirmed that, as Dr. Lindskog suspected, astrocytes are of major importance in depression. Dr. Boldizsar Czeh of the Max-Planck-Institute of Psychiatry, Munich, Germany, and colleagues took a further look at astrocytes.
They report that astrocytes “are regarded as the most abundant cell type in the brain,” but it seems they also regulate synapses, that is, the area that allows communication between neurons. They appear to control neuron development in the hippocampus.
In the journal European Neuropsychopharmacology, the team sums up all the evidence that antidepressant drugs affect astrocytes. “We propose here a hypothesis that antidepressant treatment activates astrocytes, triggering the reactivation of cortical plasticity.”
They believe that these astrocyte-specific changes probably contribute to the effectiveness of currently available antidepressant drugs, but they add that “better understanding of these cellular and molecular processes could help us to identify novel targets for the development of antidepressant drugs.”