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Drug in Class of Anti-Cancer Compounds (HDAC Inhibitors) Appears to Sharpen Memory

Can you imagine a drug that would make it easier to learn a language, sharpen your memory, and help those with dementia and Alzheimer's disease by rewiring the brain and keeping neurons alive? New Rutgers University research published in the September 23, 2015 issue of the Journal of Neuroscience found that a drug (RGFP966)administered to rats, made them more attuned to what they were hearing, able to retain and remember more information, and able to develop new connections that allowed these memories to be transmitted between brain cells. The Journal of Neuroscience article is titled “Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation.” "Memory-making in neurological conditions like Alzheimer's disease is often poor or absent altogether, once a person is in the advanced stages of the disease," said Dr. Kasia M. Bieszczad, the lead author and Assistant Professor in Behavioral and Systems Neuroscience in the Department of Psychology at Rutgers. "This drug could rescue the ability to make new memories that are rich in detail and content, even in the worst-case scenarios." What happens with dementias such as Alzheimer's is that brain cells shrink and die because the synapses that transfer information from one neuron to another are no longer strong and stable. There is currently no therapeutic treatment available that reverses this situation. The drug being tested in this animal study is among a class known as histone deacetylase (HDAC) inhibitors, now being used in cancer therapies to stop the activation of genes that turn normal cells into cancerous ones. HDAC inhibitors, in general, act to transcriptionally activate certain genes and to inactivate certain other genes. The molecules function by inhibiting the deacetylation of histones and of transcription factors, with varying effects on gene transcription. In the brain, the RGFP966 drug makes the neurons more plastic, better able to make connections, and create positive changes that enhance memory.

Researchers found that laboratory rats, taught to listen to a certain sound in order to receive a reward, and given the drug after training, remembered what they learned and responded correctly to the tone at a greater rate than those not given the drug.

Scientists also found that the rodents were more "tuned in" to the relevant acoustic signals they heard during their training, an important finding, Dr. Bieszczad said, because setting up the brain to better process and store significant sounds is critical to human speech and language.

"People learning to speak again after a disease or injury, as well as those undergoing cochlear implantation to reverse previous deafness, may be helped by this type of therapeutic treatment in the future," said Dr. Bieszczad.

"The application could even extend to people with delayed language learning abilities or people trying to learn a second language."

This hypersensitivity in processing auditory information enabled the neurons to reorganize and create new pathways, allowing more of the information that was learned to become a long-term memory, said Dr. Bieszczad who collaborated on this study with colleagues in the Department of Neurobiology and Behavior at the University of California (UC) Irvine.

"People normally remember an experience with limited detail, not everything we see, hear and feel is remembered," she said. "What has happened here is that memory becomes closer to a snapshot of the actual experience instead of being sparse, limited, or inaccurate."

[Press release] [Journal of Neuroscience abstract]