Depression

Existing drugs used to treat depression are mostly aimed at a set of chemicals in the brain (including serotonin), but they don’t work effectively in up to half of the patients who take them.  Dr. Chetkovich’s lab has recently made the novel discovery that a family of molecules in the brain (called HCN channels) is important for depression behaviors in mice. Specifically, they found that removing HCN channel genes lowers HCN channel activity and makes mice behave as if they are taking anti-depressants. HCN channels are also expressed in the heart, and existing drugs that block the HCN channels causes heart rhythm problems that make them not safe for trials to treat depression. Dr. Chetkovich recently uncovered a new way to block these channels only in the brain. He reasoned that finding a drug to block brain-specific HCN channels could lead to safe and totally unique treatments for depression that might work in those in whom existing treatments do not.
His 2012 Seed Grant will allow him to screen a large number of chemical compounds in a Drug Discovery compound library with the goal of finding new chemicals that block the channel function only in the brain. They will then test the effective chemicals from the screen in different studies in test tubes and live cells, in order to confirm that the compounds indeed block the function of the channels in living cells. The compounds identified in this proposal will serve as the basis for future efforts to test and design new drugs for treating depression. These drugs would hold exceptional promise for patients with difficult-to-treat depression, because they are targeting a different brain pathway than all existing treatments for depression.

Other Grants

Sarah C. Goetz, Ph.D., Duke University
Uncovering a Novel Role for Primary Cilia in Eph/Ephrin Signaling in Neurons
2022 Seed GrantSarah C. Goetz, Ph.D. Duke University Women’s Council Seed Grant Primary cilia are tiny projections from cells that function like an antenna- they receive and may also send…
Erin M. Gibson, Ph.D., Stanford University
Circadian Regulation of Oligodendroglial Senescence and Metabolomics in Aging
2022 Seed GrantErin M. Gibson, Ph.D.Stanford University The brain consists of two main classes of cells, neurons and glia. Glia make-up more than half of the cells in the brain…
Yvette Fisher, Ph.D., University of California, Berkeley
Dynamic Modulation of Synaptic Plasticity During Spatial Exploration
2022 Seed GrantYvette Fisher, Ph.D.University of California, Berkeley The Virginia (Ginny) & Roger Carlson Seed Grant Cognitive flexibility is critical for appropriately adjusting thoughts and behaviors to meet changing demands…
Byoung Il Bae, Ph.D., University of Connecticut
Unique Vulnerability of Developing Human Cerebral Cortex to Loss of Centrosomal Protein
2022 Seed GrantByoung Il Bae, Ph.D.University of Connecticut Carl & Marilynn Thoma Foundation Seed Grant The cerebral cortex is the largest and outermost part of the human brain. It is…