healthmedicinet

Research from the Oklahoma Medical Research Foundation reveals a new complexity to nerve cells in the brain that could affect future therapies aimed at altering mood and memory in humans.

OMRF scientist Kenneth Miller, Ph.D., studied the function of a common protein (known as CaM Kinase II) in tiny roundworms called C. elegans. His research appears in the latest issue of the journal Genetics.

“CaM Kinase II is very abundant in the brain, so it has been heavily studied,” Miller said. “But this is the first time anybody has seen results like this.”

Using a method called “forward genetics,” Miller’s lab randomly screened thousands of mutant worms for defects in neuropeptide storage and unexpectedly identified mutant worms lacking CaM Kinase II. Further analysis revealed that CaM Kinase II plays a significant role in controlling when and where neuropeptides are released from neurons.

Neuropeptides are small protein-like molecules that nerve cells in the brain use to communicate with each other. Disruptions in that communication can affect learning, memory, social behaviors and mood. They are created and stored in containers called dense-core vesicles. Under normal conditions they are only released from those containers in response to appropriate signals in the brain.

“We tagged the neuropeptides with a fluorescent protein so we could see where they went,” Miller said. “In the worms that were missing the gene that makes CaM Kinase II, the neuropeptides were virtually missing altogether in the parts of the neurons where we expected them.”

That’s because without the protein, the dense core vesicles couldn’t hold onto the neuropeptides. Instead they were all released before they got transported to their storage location, he said. In humans, such an event would be extremely unpredictable, possibly even causing a psychotic episode, Miller said.