Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
Roundworm study suggests alternatives for treatment of schizophrenia

Roundworm study suggests alternatives for treatment of schizophrenia

A group of Brazilian scientists have long conducted experiments with roundworms to investigate the role of schizophrenia-linked genes in patients’ response to antipsychotic drugs. The results obtained thus far point to new ways of understanding resistance to certain classes of medication.

The studies are conducted by researchers in the Pharmacology Department of the Federal University of São Paulo’s Medical School (EPM-UNIFESP), collaborating with colleagues at the University of Campinas (UNICAMP). An article on some of the findings has been published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry.

Schizophrenia is a highly complex mental disorder with unknown causes and no cure. Pharmacological treatment consists basically of the administration of antipsychotic drugs that control symptoms and help the patient manage social interaction. First- and second-generation antipsychotics act on the nervous system, mainly by blocking two neurotransmitters, dopamine and serotonin, which play several important roles in the brain.

First-generation or typical antipsychotics are dopamine receptor blockers. Second-generation or atypical antipsychotics block both dopamine and serotonin receptors. Some individuals with schizophrenia do not respond to typical antipsychotics and are considered treatment-refractory patients.

The group’s latest study set out to determine at the molecular level why some patients respond to second-generation but not first-generation antipsychotics.

“Schizophrenic patients are known to have lower levels of activity of a specific enzyme called NDEL1 [nuclear distribution element-like 1]. The levels of activity are even lower in treatment-resistant patients,” said Mirian Hayashi, a professor at EPM-UNIFESP and principal investigator for the study.

Hayashi explained that NDEL1 contributes to the degradation of neurotransmitters that play an important role in the brain’s functioning. “In our study, we found that NDEL1 may be linked to the development of schizophrenia,” she said.

One way to characterize the action of a protein is to use animals that have been genetically modified so as not to express the molecule of interest. These are known as knockout animals.

“We normally use mice or rats as animal models, but in the specific case of our research on NDEL1, this isn’t possible. Embryos of rodents that don’t express NDEL1 aren’t viable – they don’t develop in utero,” Hayashi said.

The alternative is to use an invertebrate, Caenorhabditis elegans, a nematode or roundworm with a length of approximately 1 mm found worldwide in moist soil.

The study described in the article was supported by FAPESP – São Paulo Research Foundation. The ongoing research is part of the National Institute of Science and Technology in Bioanalysis, which is funded by FAPESP and Brazil’s National Council for Scientific and Technological Development (CNPq).

Common ancestor

C. elegans lacks the gene that encodes NDEL1, but it has other similar genes. Nuclear distribution elements or NDE genes are present in the genomes of fungi and of vertebrates and invertebrates, such as insects, mollusks and nematodes.

This is because NDEs were inherited from a common ancestor of fungi and animals that lived more than 1.5 billion years ago. Since then, the ancestral gene has changed as new groups of living beings evolved, but its function has remained similar.

In mammals, for example, NDE1 and NDEL1 play an important role in brain development and neuron guidance. In C. elegans, the same functions are encoded by the genes NUD-1 and NUD-2.

“We decided to use C. elegans nematodes that had been genetically modified to suppress NUD-1 and NUD-2 and treat them with antipsychotics used to treat schizophrenia. The idea was to investigate the importance of these proteins in schizophrenics,” Hayashi said.

The study began with suppression of the NUD genes in nematodes divided into three groups. The control group comprised unmodified nematodes. The second and third strains consisted of knockout strains in which either NUD-1 or NUD-2 had been silenced.

The groups were treated with a typical antipsychotic (a first-generation drug that blocks dopamine receptors), an atypical antipsychotic (a second-generation drug that blocks dopamine and serotonin receptors), or saline as a control.

“For the experiments, we used these three strains and compared the behavior of each one with and without treatment via the first-generation drug [haloperidol] or the second-generation drug [clozapine], which were administered separately,” Hayashi said.

“To evaluate the role of NUD genes and antipsychotic drugs in the behavior of C. elegans, we measured the frequency of body movement [locomotion], oviposition [egg laying], and pharyngeal pumping. All these are characteristics controlled by neurons and specific neurotransmitters such as dopamine and serotonin, which are involved in schizophrenia.”

C. elegans is tiny, and the researchers used a magnifying glass to observe the worms used in these experiments. Each group comprised between six and ten worms. To infer whether they were affected by the drugs, in the specific case of locomotion, the researchers observed their movements and the distances traveled.

“Frequent zigzagging movements were considered a sign of action by the drugs. This enabled us to establish whether the absence of NUD genes influenced the effectiveness of the drugs in acting on the dopamine and serotonin pathways,” Hayashi said.

Egg-laying behavior was analyzed by counting the number of eggs. In the case of pharyngeal pumping, the scientists observed whether feeding rates were normal or displayed alterations.

“The findings suggest that the absence of NUD and hence of the enzyme expressed by this gene may influence the response to these drugs. The activity of NDEL1 could therefore predict the response to treatment,” Hayashi said.

About author

Related Articles