Why do antipsychotics take so long to kick in?
|National Library of Medicine
Antipsychotic drugs have been used clinically since the 1970s, but it’s not yet clear why it takes three or more weeks for them to become fully effective. A team led by Eric Klann and Moses Chao at New York University analyzed neurons in culture and in live mice to see what happened at the molecular level when neurons were exposed to haloperidol, a first-generation drug for schizophrenia. Previous studies had shown that the drug acts on the kinase Akt. The Klann and Chao laboratories have a longstanding interest in an Akt pathway that involves a protein complex called mTORC1. This Akt-mTORC1 pathway is important for protein synthesis. The investigators showed that Akt became activated and turned on mTORC1 when haloperidol was given to neurons. The activation of this pathway led to increased protein synthesis. The cells made more proteins involved in mRNA translation, which was followed by production of more cytoskeletal proteins. The neurons also appeared to become morphologically more complex, creating more branches to make more connections with other neurons. Klann says some of the proteins they found “were also reported as being altered in the brains of both (autopsied) rodents and human patients treated chronically with antipsychotics.” One question the work raises is “whether or not chronic administration of haloperidol would maintain the morphological complexity or if this is an initial response that declines over time,” says Klann. The work was published in the journal Science Signaling.
Sniff-n-scratch: how mosquitoes sniff us out
A team led by Anandasarkar Ray at the University of California, Riverside, identified an important class of neurons in mosquitoes that detect our skin odors. Mosquitoes follow carbon dioxide emitted when we breathe, and, once close enough, dive toward our bare skin, attracted by its odors. While the neuron that picked up carbon dioxide had been known, the identity of the neuron or neurons with odor receptors that attracted mosquitoes to human skin scents remained elusive. For years, Ray and colleagues looked for human-skin odor receptors on the complex mosquito antenna. They ignored the simpler maxillary palp organs small, fingerlike sensory structures that contain the carbon dioxide receptors. Conventional wisdom was that the carbon dioxide receptor “was narrowly tuned, responding primarily to carbon dioxide,” says Ray. But they recently found “the carbon dioxide receptor is an extremely sensitive detector of several skin odorants,” says Ray. “In fact, it is far more sensitive to some of these odor molecules when compared to carbon dioxide.” To see if the carbon dioxide receptor neuron, called cpA, can be targeted by chemicals that might be developed as mosquito traps, the investigators screened nearly half a million compounds to find ones that either activated or shut down cpA. They settled on two compounds: ethyl pyruvate, a fruity-smelling cpA inhibitor used as a flavor agent in food, and cyclopentanone, a minty-scented cpA activator used as a flavor and fragrance agent. Ethyl pyruvate substantially reduced the mosquitoes’ attraction toward a human arm, in effect acting as a repellent. Cyclopentanone, meanwhile, lured mosquitoes, so it could be used as an attractant in a trap. The work was published in the journal Cell.