Johns Hopkins researchers at Society for Neuroscience Annual Meeting

(Press-News.org) Oct. 13-17, 2012 Ernest N. Morial Convention Center
900 Convention Center Boulevard, New Orleans, La. 70130

IN ANIMALS, DRUG PREVENTS NERVE DAMAGE CAUSED BY CHEMOTHERAPY, HIV AND DIABETES

Poster#: 354.19/T6, Hall F-J, Monday, Oct. 15, 2012, 9-10 a.m. CST
Authors: J. Zhu, W. Chen, C. Zhou, N. Reed, A. Hoke AND Poster#: 354.29/T16, Hall F-J, Monday, Oct. 15, 2012, 11 a.m.-12 p.m. CST
Authors: M. Ray, N. Reed, J. Zhu, A. Hoke

Johns Hopkins researchers have identified a drug that seems to protect mice and rats from nerve degeneration caused by chemotherapy drugs, HIV and diabetes. Almost 20 million Americans suffer from nerve damage caused by chronic disease, infection or exposure to toxic chemicals, like the ones used to treat cancer. Nerve damage can cause numbness, tingling, pain and trouble walking. Although pain relievers can provide some relief, according to Ahmet Hoke, M.D., Ph.D., professor of neurology at the Johns Hopkins School of Medicine, there aren't any treatments on the market that prevent further nerve damage or repair injured nerves. To find neuroprotective drugs, Hoke's research team treated nerve cells grown in a dish with Taxol, a chemotherapy drug that causes nerve damage, also known as neuropathy, and one of 2,000 different compounds from a collection that was put together by a consortium funded by the National Institute of Neurological Disorders and Stroke to find treatments for neurodegenerative diseases. By looking in a microscope for healthy nerve cells — ones without damaged, shriveled appendages — in the presence of Taxol, they identified the protective drug ethoxyquin. Ethoxyquin effectively prevented 70 percent of the nerve damage in mice treated with Taxol, as well as protected the nerves in diabetic rats and in the mouse model of HIV. "Ethoxyquin or other drugs developed based on ethoxyquin's molecular structure will be important for developing neuroprotective therapies — a hugely unmet clinical need," says Hoke. He cautions that safety studies still need to be carried out before clinical trials are considered. While investigating how ethoxyquin works, the researchers found the drug binds to a protein involved in the cell's stress response system. Further elucidation of ethoxyquin's method of action may help identify other targets for neuropathy treatment. ENVIRONMENTAL CUES AND HORMONE LEVELS CONTROL BRAIN STRUCTURE IN CANARIES

Poster#: 503.09/EEE57, Hall F-J, Monday, Oct. 15, 2012, 1-2 p.m. CST
Authors: B. A. Alward, T. J. Stevenson, K. Y. Peng, M. L. Rouse, W. D. Mayes, J. Balthazart, G. F. Ball AND Poster#: 503.10/EEE58, Hall F-J, Monday, Oct. 15, 2012, 2-3 p.m. CST
Authors: M. L. Rouse, Jr., S. Dangelmajer, G. F. Ball

Early in the 20th century, bird dealers discovered that female birds injected with the sex hormone testosterone sang more complicated songs, like their male counterparts. A Johns Hopkins research team decided to investigate how female canary brains changed with exposure to testosterone to affect their behavior. Greg Ball, Ph.D., professor of psychological and brain sciences at the Zanvyl Krieger School of Arts and Sciences, says birds learn to sing by mimicking their fathers, and use memory to recall songs, which is similar to how people learn to talk. Therefore the researchers quantified the levels of learning and memory genes — thought to affect the development of male-typical singing behavior — in the brains of female birds treated with testosterone for one to five weeks. The researchers discovered increased levels of the gene for the glutamate receptor, NMDAr, in the region of the brain that controls singing. NMDAr detects glutamate, one of the brain's chemical messengers, and is important for song learning. "We want to continue to explore how internal hormonal and external environmental cues normally affect behavior by changing the brain," says Ball. "Understanding what happens under different hormonal conditions in the brain, even in birds, provides insight on what happens in the case of humans with mental disorders, where problems in the brain adversely affect behavior." STUDYING MEMORY IN AN AMNESIAC ARTIST

Poster#: 489.24/ZZ6, Hall F-J, Monday, Oct. 15, 2012, 4-5 p.m. CST
Authors: Emma Gregory, Michael McCloskey, Katherine Kelliher and Barbara Landau

Emma Gregory, Ph.D., a postdoctoral researcher in cognitive science at the Zanvyl Krieger School of Arts and Sciences at The Johns Hopkins University, studied whether retrograde amnesia (loss of memory for information acquired before the onset of an illness or trauma) affected a broader range of knowledge than those tested in most previous studies of amnesia. Her team's subject is a 62-year-old woman, LSJ, who was a very successful commercial artist before suffering a bout of viral encephalitis — which extensively damaged her temporal lobe — in 2007. In the study, Gregory's team explored potential differences between how the illness affected LSJ's everyday knowledge, such as commercial logos and famous people's faces, and expert knowledge, such as art and music that were peculiar to the subject's life. They found severe impairment across all domains tested, suggesting that the temporal lobes may be critical for diverse forms of world knowledge and that the two categories of knowledge (everyday and expert) may not be distinct categories in memory. The team's results lay a foundation for more detailed investigations into how the human brain stores world knowledge, and how this knowledge is disrupted when the brain is damaged. A video about this study is available here: http://www.youtube.com/watch?feature=player_embedded&v=gp4dRSK5UR4

EXPLORING A NEW GENETIC CAUSE OF ALS

Talk/Program # 517.01, Room 277, Tuesday, Oct. 16, 2012, 8- 8:15 a.m. CST
Authors: C. J. Donnelly, L. W. Ostrow, P.-W. Zhang, S. Vidensky, N. A. Mistry, U. Balasubramanian, Y. Li, P. Tienari, N. J. Maragakis, B. J. Traynor, R. Sattler, J. D. Rothstein AND Poster#: 858.01, Hall F-J, Wednesday, October 17, 2012, 1:00 PM - 2:00 PM
Authors: L. W. Ostrow, C. Donnelly, Y. Li, S. Vidensky, P. Tienari, N. J. Maragakis, B. J. Traynor, J. D. Rothstein

Last year, researchers in a multi-institutional study discovered a DNA change found to be the cause of more than 40 percent of inherited and 10 percent of spontaneous cases of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Up to this point, no other reliable genetic cause was known for the most common, sporadic form of these progressive neurodegenerative diseases. By studying how this ALS genetic change affects neurons and glial cells — the neurons' support cells — Johns Hopkins researchers hope to develop new therapies for the disease. The team took skin biopsies from patients with this form of ALS, and converted the skin cells to induced pluripotent stem (iPS) cells — stem cells that can be coaxed into other cell types — and then into neurons and glia using the latest stem cell culture techniques. First, the researchers examined the extent to which the level of genes in the ALS stem cells were turned up or down in comparison to cells from healthy people. They found at least four genes reliably changed levels in the ALS neurons, and also found the same changes in brain tissue from deceased ALS stem cells. By using gene therapy to add pieces of DNA into the ALS stem cells, the researchers reduced the levels of one of the genes to that of normal neurons. "These stem cell assays have already allowed use to discover drugs that normalize the gene levels like the gene therapy did to search for ALS treatments," says Jeffrey Rothstein, M.D., Ph.D., director of the Brain Science Institute and the Robert Packard Center for ALS Research at the Johns Hopkins University School of Medicine. "Unfortunately, it's too early to say if restoring the gene levels will treat the disease. But, it's an important lead and an exciting way to approach ALS therapy."

USING NASAL BIOPSIES TO STUDY THE CAUSE OF SCHIZOPHRENIA

Talk/Program#: 521.05, Room 395, Tuesday, Oct. 16, 2012, 9-9:15 a.m. CST
Authors: C.-Y. Lin, Y. Horiuchi, K. Ishizuka, A. Sawa

Using tissue biopsies from the thin lining of the nasal passages from people with mental disorders, Johns Hopkins researchers are collecting genetically unaltered stem cells to better study the cause of diseases like schizophrenia and bipolar disorder. Akira Sawa, M.D., Ph.D., professor of psychiatry and director of the Schizophrenia Center at the Johns Hopkins University School of Medicine, and his colleagues have found a way to separate out the stem cells from the nasal passages and coax them into neurons in a procedure they say will provide an alternative patient cell source that leaves the chemical marks on genomes' DNA sequences intact. The standard approach for obtaining patient cells to study diseases uses induced pluripotent stem (iPS) cells — cells taken from the blood or a skin biopsy that are converted to a stem cell state by adding extra DNA. The stem cells are then converted to a cell type of choice. According to the researchers, unlike iPS cells, those garnered from nasal biopsies do not have changes to their epigenetics features — the heritable information in the DNA other than the DNA sequence itself, like the presence of extra chemical modifications on the DNA letters. Epigenetics may play a crucial role in many complex diseases where single genetic causes or specific groups of genes don't appear to contribute to disease, like in heart disease, autism or schizophrenia. "If we only use iPS cells to study these types of diseases, we might miss the key epigenetic causes," says Sawa. "Both types of cells have clear advantages and disadvantages that if studied together can provide a complementary approach to better understanding mental disorders." He noted that the nasal biopsy cells are faster to culture, but these cells can't be converted to as many different types of neurons as iPS cells. Using these nasal biopsy cells, the Sawa lab hopes to uncover molecular, especially epigenetic, causes for mental disorders, which would allow for the development of new therapeutics. BLOOD PRESSURE-REDUCING HYDROGEN SULFIDE GAS ALSO IMPLICATED IN PAIN SENSATION

Poster#: 784.06/NN10, Hall F-J, Wednesday, Oct. 17, 2012, 9-10 a.m. CST
Authors: P. Scherer, R. Barrow, T. Sakamoto, A. Mustafa, B. Paul, R. Xu, S. Vandiver, M. Caterina and S. H. Snyder

Hydrogen sulfide may act as a chemical messenger for pain sensation, in addition to its role as a blood pressure regulator, according to Johns Hopkins researchers. A few years ago, Solomon Snyder, M.D., professor of neuroscience at the Johns Hopkins University School of Medicine, and his research team discovered that hydrogen sulfide relaxes blood vessels and thus decreases blood pressure. Researchers elsewhere had known for years that injecting hydrogen sulfide under the skin caused pain. Snyder's colleagues hypothesized that hydrogen sulfide triggered pain sensors, known as TRP channels, on the cell. To test this idea, graduate student Paul Scherer bathed mammalian cells containing the TRPA1 channel in a dye that glows in the presence of calcium. Then, Scherer treated the cells with hydrogen sulfide and observed cells' insides lighting up, indicating the TRPA1 channels responded to the gas. Scherer wanted to know how hydrogen sulfide stimulated the channel. He hypothesized that the gas was chemically reacting with the amino acids that make up the channel. The amino acid cysteine was a likely candidate since it contains a chemical group that is known to react with hydrogen sulfide. To test his idea, Scherer converted the cysteines in the TRPA1 channel protein to a form that isn't chemically reactive to hydrogen sulfide. Cells making this cysteine-modified TRPA1 channel bathed in the calcium dye were treated with hydrogen sulfide gas. The cells no longer lit up, indicating the hydrogen gas no longer stimulated the TRPA1 channel when it could no longer react chemically with the channel. "If further studies confirm that hydrogen sulfide gas does cause pain sensation," says Scherer, "perhaps tinkering with hydrogen sulfide gas production could be an avenue for ameliorating chronic or acute pain." JOHNS HOPKINS RESEARCHER RECEIVES YOUNG INVESTIGATOR AWARD

EMBARGOED UNTIL Oct. 13, 11 a.m. CST

Guo-li Ming, M.D., Ph.D., professor of neurology and member of the Institute for Cell Engineering, will receive a Young Investigator Award from the Society of Neuroscience. The award, recognizing outstanding achievements from researchers completing advanced degrees within 10 years, will be presented at the Society for Neuroscience annual meeting held in New Orleans, from Oct. 13 to 17, and includes a cash prize of $15,000. Ming studies early brain development, and how early developmental defects can lead to mental disorders.

http://www.hopkinsmedicine.org/institute_cell_engineering/experts/guo_ming.html JOHNS HOPKINS RESEARCHER RECEIVES THE GRUBER INTERNATIONAL RESEARCH AWARD IN NEUROSCIENCE

EMBARGOED UNTIL Oct. 13, 11 a.m. CST

Junjie Guo, Ph.D., a native of China, was awarded The Peter and Patricia Gruber International Research Award in Neuroscience for his research accomplishments in an international setting. The award, which includes a $25,000 prize, will be awarded at the annual Society for Neuroscience Conference in New Orleans, from Oct. 13 to 17. Last year, Guo completed his Ph.D. dissertation in the laboratory of Hongjun Song, Ph.D., in the Institute for Cell Engineering, showing that chemical modifications to the DNA in brain stem cells change as the cells mature into neurons. He now has a postdoctoral fellowship at the Whitehead Institute at the Massachusetts Institute of Technology.

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