(Press-News.org) Using human induced pluripotent stem cells (hiPSCs), researchers have gained new insight into what may cause schizophrenia by revealing the altered patterns of neuronal signaling associated with this disease. They did so by exposing neurons derived from the hiPSCs of healthy individuals and of patients with schizophrenia to potassium chloride, which triggered these stem cells to release neurotransmitters, such as dopamine, that are crucial for brain function and are linked to various disorders. By discovering a simple method for stimulating hiPSCs to release neurotransmitters, the findings in the International Society for Stem Cell Research's journal Stem Cell Reports, published by Cell Press, could provide new insights into how neurons communicate with each other and could lead to a better understanding of the neural mechanisms underlying a range of brain disorders.
"This study is novel because it shows that stem cell neurons derived from patients can provide new insight into neurotransmitter mechanisms occurring in brain disorders such as schizophrenia," says senior study author Vivian Hook of the University of California, San Diego. "The approach of this study has broad opportunities for uncovering the neurochemistry of brain cell communication in numerous brain disorders, via these studies of human disease in a dish. Findings from these studies will lead to new therapeutic strategies for brain disorders, especially those mental and neurological diseases for which no drug treatments exist today."
hiPSCS are cells that are taken from adults, genetically reprogrammed to an embryonic stem cell-like state, and then converted into specialized cells such as neurons. Patient-derived hiPSCs offer the possibility of modeling an individual's disease in a dish and assessing which drugs will most effectively treat the disease. Because dysfunction in neural communication is linked to brain disorders such as schizophrenia, Hook and Fred Gage of The Salk Institute and Kristen Brennand of the Icahn School of Medicine at Mount Sinai set out to determine whether hiPSC-derived neurons can be induced to release important brain signaling chemicals, allowing disease mechanisms to be studied in a dish.
To address this question, the researchers exposed hiPSC-derived neurons from healthy individuals and patients with schizophrenia to a chemical known to stimulate the release of neurotransmitters. They found that these cells contained neurotransmitter-producing enzymes and were capable of secreting dopamine, norepinephrine, and epinephrine—neurotransmitters that are crucial for brain function and that are linked to various disorders. Moreover, secretion of the three neurotransmitters was enhanced in hiPSC-derived neurons from schizophrenia patients compared with those from healthy individuals.
"The significance of this study is that patient-derived stem cell neurons can uncover previously unknown neurotransmitter brain mechanisms occurring in schizophrenia," Hook says. "Because in vivo human brain research is limited, hiPSC neurons derived from patients create new opportunities to understand changes occurring in brain cells occurring in nervous system disorders. These approaches can potentially define new drug targets for the development of therapeutic agents to improve the lives of schizophrenia patients."
INFORMATION:
Stem Cell Reports, Hook et al.: "Human iPSC Neurons Display Activity-Dependent Neurotransmitter Secretion: Aberrant Catecholamine Levels in Schizophrenia Neurons."
Stem cells help researchers understand how schizophrenic brains function
2014-09-11
ELSE PRESS RELEASES FROM THIS DATE:
Intestinal bacteria needed for strong flu vaccine responses in mice
2014-09-11
Mice treated with antibiotics to remove most of their intestinal bacteria or raised under sterile conditions have impaired antibody responses to seasonal influenza vaccination, researchers have found.
The findings suggest that antibiotic treatment before or during vaccination may impair responses to certain vaccines in humans. The results may also help to explain why immunity induced by some vaccines varies in different parts of the world.
In a study to be published in Immunity, Bali Pulendran, PhD, and colleagues at Emory University demonstrate a dependency on gut ...
Our microbes are a rich source of drugs, UCSF researchers discover
2014-09-11
Bacteria that normally live in and upon us have genetic blueprints that enable them to make thousands of molecules that act like drugs, and some of these molecules might serve as the basis for new human therapeutics, according to UC San Francisco researchers who report their new discoveries in the September 11, 2014 issue of Cell.
The scientists purified and solved the structure of one of the molecules they identified, an antibiotic they named lactocillin, which is made by a common bacterial species, Lactobacillus gasseri, found in the microbial community within the vagina. ...
Cells put off protein production during times of stress
2014-09-11
DURHAM, N.C. -- Living cells are like miniature factories, responsible for the production of more than 25,000 different proteins with very specific 3-D shapes. And just as an overwhelmed assembly line can begin making mistakes, a stressed cell can end up producing misshapen proteins that are unfolded or misfolded.
Now Duke University researchers in North Carolina and Singapore have shown that the cell recognizes the buildup of these misfolded proteins and responds by reshuffling its workload, much like a stressed out employee might temporarily move papers from an overflowing ...
A non-toxic strategy to treat leukemia
2014-09-11
A study comparing how blood stem cells and leukemia cells consume nutrients found that cancer cells are far less tolerant to shifts in their energy supply than their normal counterparts. The results suggest that there could be ways to target leukemia metabolism so that cancer cells die but other cell types are undisturbed.
Harvard Stem Cell Institute scientists at the Massachusetts General Hospital Center for Regenerative Medicine and the Harvard University Department of Stem Cell and Regenerative Biology led the work, published in the journal Cell, in collaboration with ...
Scientists discover neurochemical imbalance in schizophrenia
2014-09-11
Using human induced pluripotent stem cells (hiPSCs), researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California, San Diego have discovered that neurons from patients with schizophrenia secrete higher amounts of three neurotransmitters broadly implicated in a range of psychiatric disorders.
The findings, reported online Sept. 11 in Stem Cell Reports, represent an important step toward understanding the chemical basis for schizophrenia, a chronic, severe and disabling brain disorder that affects an estimated one in 100 persons at some ...
Diverse gut bacteria associated with favorable ratio of estrogen metabolites
2014-09-11
Washington, DC—Postmenopausal women with diverse gut bacteria exhibit a more favorable ratio of estrogen metabolites, which is associated with reduced risk for breast cancer, compared to women with less microbial variation, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).
Since the 1970s, it has been known that in addition to supporting digestion, the intestinal bacteria that make up the gut microbiome influence how women's bodies process estrogen, the primary female sex hormone. The colonies of bacteria ...
Puerto Ricans who inject drugs among Latinos at highest risk of contracting HIV
2014-09-11
Higher HIV risk behaviors and prevalence have been reported among Puerto Rican people who inject drugs (PRPWID) since early in the HIV epidemic. Now that HIV prevention and treatment advances have reduced HIV among PWID in the US, researchers from New York University's Center for Drug Use and HIV Research (CDUHR) examined HIV-related data for PRPWID in Puerto Rico (PR) and Northeastern US (NE) to assess whether disparities among PRPWID continue.
The study, "Addressing the HIV/AIDS epidemic among Puerto Rican people who inject drugs: the Need for a Multi-Region Approach," ...
Chemical signals in the brain help guide risky decisions
2014-09-11
A gambler's decision to stay or fold in a game of cards could be influenced by a chemical in the brain, suggests new research from the University of British Columbia.
The rise and fall of dopamine plays a key role in decisions involving risk and reward, from a baseball player trying to steal a base to an investor buying or selling a stock. Previous studies have shown that dopamine signals increase when risky choices pay off.
"Our brains are constantly updating how we calculate risk and reward based on previous experiences, keeping an internal score of wins and losses," ...
Mice and men share a diabetes gene
2014-09-11
A joint work by EPFL, ETH Zürich and the CHUV has identified a pathological process that takes place in both mice and humans towards one of the most common diseases that people face in the industrialized world: type 2 diabetes.
This work was conducted in Johan Auwerx's (EPFL) and Ruedi Aebersold's (ETH Zürich) laboratories, and succeeded thanks to the combination of each team's strengths. The relevance of their discovery, published today in Cell Metabolism, results from their joint effort.
In Lausanne, the researchers carried out a detailed study of the genome and ...
Compound protects brain cells after traumatic brain injury
2014-09-11
A new class of compounds has now been shown to protect brain cells from the type of damage caused by blast-mediated traumatic brain injury (TBI). Mice that were treated with these compounds 24-36 hours after experiencing TBI from a blast injury were protected from the harmful effects of TBI, including problems with learning, memory, and movement.
Traumatic brain injury caused by blast injury has emerged as a common health problem among U.S. servicemen and women, with an estimated 10 to 20 percent of the more than 2 million U.S. soldiers deployed in Iraq or Afghanistan ...