In order to understand memory deficit and neuronal loss in mouse models of Alzheimer’s disease, the Bright Focus Foundation, a non profit dedicated to supporting research on Alzheimer’s disease as well as macular degeneration and glaucoma, awarded a grant to Max Planck Florida Institute for Neuroscience (MPFI) researchers, Ryohei Yasuda, Ph.D., Scientific Director and Erzsebet Szatmari, Ph.D. Previous studies from the Yasuda Lab have shown that when beta-amyloid is increased in an animal’s brain, so is the level of a protein, called centaurin a1 (CentA1). The two scientists sought to understand how CentA1 might be involved in the Alzheimer’s disease process using mouse models of the disease.
Over half a century ago, Dr. Alois Alzheimer cared for a patient who was slowly losing more and more of her memories and herself. Upon her death, he examined her brain, and identified what are now considered the two main biomarkers for Alzheimer’s disease: plaques and tangles. Plaques are clumps of proteins that build up between neurons and interfere with their ability to communicate. Tangles have a similar effect inside the neurons. Decades later, scientists have observed that the severity of the disease directly correlates with the number of plaques in a patient’s brain, and that the plaques consist mainly of a particular protein called beta-amyloid. Over the past twenty years, five drugs have been approved to treat the symptoms of Alzheimer’s disease, but none have been able to prevent the degenerative action of these plaques.
They suspected that the protein may be produced in response to beta-amyloid and play a role in protecting neurons from degeneration. They were surprised to discover that when the protein was removed, neurons in culture actually grew more connections to surrounding neurons. It seemed CentA1 was not protective at all, but actually involved in elimination of dendritic spines, the sites of neuronal connections. To examine whether removing CentA1 from the brain might have an effect on memory formation, the group has developed mice that lack the CentA1 protein (CentA1 KO).
The Bright Focus Foundation’s grant will support undergoing experiments that will address two questions: First, Is learning and memory improved in mice lacking CentA1? Second, if it is, will lack of this protein restore memory loss in Alzheimer’s disease model mice?
In order to test the effect of CentA1 KO on memory of these mice, the scientists will use behavioral tests that evaluate spatial memory and fear memory. The scientists are developing the tests in collaboration with the laboratory of Bob Stackman, Ph.D., Associate Professor at Florida Atlantic University (FAU). Szatmari and Stackman met when Stackman gave a talk about his laboratory’s work in behavioral neuroscience as a part of a TINSS lecture series connecting local scientists from MPFI, Scripps Research Institute, Florida and FAU. Szatmari says she immediately knew that the laboratory’s studies could benefit from the expertise of Stackman’s team. Soon after the seminar, Yasuda and Stackman started a formal collaboration that they hope will extend to other projects in the Yasuda Lab. The group is also collaborating with world-renowned Alzheimer’s disease scientists from Mayo Clinic Florida, who will examine human Alzheimer’s brains for signs of misregulation of CentA1 signaling.
Yasuda’s team points out that the preliminary results are promising and that the mice lacking CentA1 perform significantly better than normal mice on a variety of behavioral tests. “We hope that understanding of the molecule CentA1 will provide new therapeutic targets for treating Alzheimer’s disease in the future.” Yasuda said.
They’re pesky and annoying when they get into your fruit, but Drosophila melanogaster, more affectionately known as the “fruit fly,” are helping researchers at Florida Atlantic University to discover novel genes that are responsible for neuroprotection.
In a recent publication in Nature Scientific Reports, titled “Pushing the Limit: Examining Factors that Affect Anoxia Tolerance in a Single Genotype of Adult D. Melanogaster,” Monica G. Risley, a Ph.D. student working in the laboratory of Ken Dawson-Scully, Ph.D., associate professor in FAU’s Charles E. Schmidt College of Science, and co-authors, had an unexpected discovery involving fruit flies, drowning and comas.
Insects enter into a deep state of sleep-like coma when deprived of oxygen caused by a slowing of their metabolism. You can see this in insects floating in a swimming pool. Have you ever wondered what happened to that insect on the side of the pool, just lying there and then disappearing? It’s likely that the insect dried off, woke up, and flew away. Although this phenomenon has been previously known, the limits of insect drowning while examining age, temperature, and drowning time have finally been brought together in this FAU study.
As expected, a young fruit fly can survive up to 12 hours drowning in a puddle of water and fly away unharmed. The unexpected discovery by Risley, Dawson-Scully and collaborators was that in cold weather of 40 degrees Fahrenheit, this coma can be stretched to three full days (72 hours).
“These fruit flies are able to withstand three days of drowning by putting themselves into a reversible coma that preserves vital energy stores,” said Risley. “One of the really interesting facets of our study is that age plays a major role in the drowning response. Older flies survive poorly compared to younger flies in response to this drowning stress and low oxygen.”
In the recent past fruit flies have been used to successfully model a number of human disorders such as Alzheimer’s, Parkinson’s and obesity. They provide an ideal system to study cellular pathways associated with neural failure following severe trauma, and to help researchers develop novel therapies targeting molecules that contribute to neural dysfunction and cell death/damage.
“Adapted animals, such as insects, employ genetic, molecular, and physiological strategies to prevent specific neurological pathologies resulting from stressors such as low oxygen or anoxia, high temperatures or hyperthermia, and high levels of free radicals or oxidative stress,” said Dawson-Scully.
Risley and her collaborators will take the findings from this important study and apply them to future works, using the genetically tractable fruit fly at different ages, to try and understand mechanisms of age-related disease susceptibilities and how to protect against them at the cellular level.
The Federation of American Societies for Experimental Biology (FASEB) has honored Samuel M. Young, Jr. Ph.D., a Max Planck Research Group Leader at Max Planck Florida Institute for Neuroscience, with the Glaxo Smith Kline Neuroscience Discovery Award. The award will be presented at the Ion Regulation Conference at the end of June. As one of four recipients of the award, he will give a talk about his team’s recent research regarding the molecular mechanisms of voltage gated calcium channel regulation of the speed and efficacy of neurotransmitter release.
His group’s goal is to uncover the molecular mechanisms of how synapses sustain neurotransmitter release to meet the functional demands of different neural circuits in which they are embedded within. A major focus of their research is determining the molecular mechanisms of how voltage gated calcium channels regulate neurotransmitter release. Results of their work may have wide ranging implications in the study of migraines, neuropathic pain, ataxias, and many other neurological disorders.
The purpose of the award is to honor early-career scientists to give them a platform to share their work at the FASEB Ion Channel Regulation meeting. FASEB is a 100-year-old organization joining 120,000 researchers worldwide. Their primary goal is to support biomedical research by holding educational meetings and disseminating research results.