Breaking News
April 22, 2019 - The U.S government may account for up to $37.8 billion due to opioid epidemic
April 22, 2019 - Improving ACA’s Insurance Coverage Provisions will lead to better care for patients
April 22, 2019 - Study identifies possible therapeutic effects of curcumin on stomach cancer
April 22, 2019 - Hyaline fibromatosis syndrome – Genetics Home Reference
April 22, 2019 - Scientists use CRISPR for possible ‘bubble boy’ therapy
April 22, 2019 - Hematologist (and a mom, singer, actress and much more) stands up for diversity
April 22, 2019 - Novel AI voice tool can help diagnose PTSD
April 22, 2019 - Overlooked part of cell’s internal machinery may hold key to treating acute myeloid leukemia
April 22, 2019 - MIT scientists reverse some behavioral symptoms of rare neurodevelopmental disorder
April 22, 2019 - Scientists find new therapy target for drug-induced liver failure
April 22, 2019 - Opioid dose variability could lead to increased risk of overdose, study suggests
April 22, 2019 - Newly developed model predicts salmonella outbreaks several months in advance
April 22, 2019 - Deep-learning model better predicts survival outcomes for lung cancer
April 22, 2019 - One in Three U.S. Adults Aged 35 to 44 May Have Drinking Problem
April 22, 2019 - Why the measles virus is so contagious
April 22, 2019 - Magnet ‘Zap’ to the Brain Might Jumpstart Aging Memory
April 22, 2019 - Immune response to gut microbes may be early indicator of type 1 diabetes
April 22, 2019 - Destination Limbo: Health Suffers Among Asylum Seekers In Crowded Border Shelter
April 22, 2019 - Research shows how dopamine contributes to sex differences in worms
April 22, 2019 - Marijuana users weigh less compared to non-users
April 22, 2019 - Research uncovers critical RNA processing aberrations in ALS and FTD
April 22, 2019 - Many cancer patients use marijuana and prescription opioids, study reveals
April 22, 2019 - Frailty may up fracture risk in patients with type 2 diabetes
April 22, 2019 - Study provides new insight into how obesity, insulin resistance can affect cognition
April 22, 2019 - Study seeks to better understand the genetic causes for hypospadias
April 22, 2019 - FDA grants approval of first generic naloxone nasal spray to treat opioid overdose
April 22, 2019 - FDA authorizes marketing of first medical device to treat ADHD
April 22, 2019 - Vanderbilt researchers to develop and test ‘safe harbor’ standards of care
April 22, 2019 - You’re probably brushing your teeth wrong – here are four tips for better dental health
April 22, 2019 - Pharmacy closures contribute to medication non-adherence among heart patients
April 22, 2019 - Using Edge AI technology to observe behavior of cattle
April 22, 2019 - Bacteria play a role in the development of stomach ulcers in pigs
April 22, 2019 - Hand Hygiene Compliance Poor in Task Transitions
April 22, 2019 - smoking could harm your baby
April 22, 2019 - Scientists identify rare, paradoxical response to antiretroviral therapy
April 21, 2019 - More TV, Tablets, More Attention Issues at Age 5
April 21, 2019 - Drug reduces risk of kidney failure in people with diabetes, study finds
April 21, 2019 - New research identifies novel link between antibiotic resistance and climate change
April 21, 2019 - Simple intervention can provide lasting protection for teens against junk food marketing
April 21, 2019 - The protein p38-gamma identified as a new therapeutic target in liver cancer
April 21, 2019 - Novel system enables researchers to study bacteria within mini-tissues in a dish
April 21, 2019 - Discovery of oral cancer biomarkers could save thousands of lives
April 21, 2019 - Geneva Exhibition committee gives gold medals to two medications developed by Kazan
April 21, 2019 - Scientists aim to minimize or eliminate hair loss during cancer treatment
April 21, 2019 - WiFi interacts with signaling pathways in the human brain
April 21, 2019 - Stroke Hospitalizations Down in Black, White Medicare Enrollees
April 21, 2019 - First common risk genes discovered for autism
April 21, 2019 - Researchers map auditory sensory system of the mouse brain
April 21, 2019 - Scientists Bring Pig’s Brain, Dead 4 Hours, Back to ‘Cellular Activity’
April 21, 2019 - Virtual reality a promising tool for reducing fears and phobia in autism
April 21, 2019 - New analysis lists out opportunities for U.S. medical schools to advance population health
April 21, 2019 - More sleep may help teens with ADHD focus and organize
April 21, 2019 - Breakthrough antibody treatment suppresses HIV without antivirals
April 21, 2019 - AveXis Data Reinforce Effectiveness of Zolgensma in Treating Spinal Muscular Atrophy (SMA) Type 1
April 21, 2019 - Is your hand pain arthritis, carpal tunnel or something else?
April 21, 2019 - Measles outbreaks may become more frequent if vaccination rates continue to decline
April 21, 2019 - Researchers succeed in accelerating process of creating 3D images
April 21, 2019 - Tiny worm mimics key genetic risk for Alzheimer’s
April 21, 2019 - Angry dreams explained by brain waves
April 20, 2019 - Parenteral Antimicrobial Tx at Home Burdens Children’s Caregivers
April 20, 2019 - Diabetes treatment may keep dementia, Alzheimer’s at bay
April 20, 2019 - New bandage-like biosensor collects and analyzes sweat
April 20, 2019 - A comprehensive, centralized database of bovine milk compounds
April 20, 2019 - Two new epigenetic regulators maintain self-renewal of embryonic stem cells
April 20, 2019 - New Evidence That Veggies Beat Steak for Heart Health
April 20, 2019 - Study reveals genes associated with heavy drinking and alcoholism
April 20, 2019 - Texas A&M AgriLife becomes the newest member of NutriRECS international consortium
April 20, 2019 - In most states, insurance won’t cover addiction treatments
April 20, 2019 - Computer-based memory games may be beneficial for individuals with fragile X syndrome
April 20, 2019 - Timing of food intake influences molecular clock in the liver of mice
April 20, 2019 - Precise decoding of breast cancer cells paves way for new treatment option
April 20, 2019 - Scientists use 3D imaging to help model complex processes performed by placenta
April 20, 2019 - MediciNova Announces Plans to Move Forward with a Phase 3 Trial of MN-166 (ibudilast) in ALS
April 20, 2019 - Genetic variants that protect against obesity could aid new weight loss medicines
April 20, 2019 - New technology developed for microscopic imaging in living organisms
April 20, 2019 - when quitting cigarettes, consider using more nicotine, not less
April 20, 2019 - Key proteins can block Listeria without triggering the death of host cells
April 20, 2019 - Researchers create a working model of cerebral tract to study brain function
April 20, 2019 - New study shows that microbes can help break toxic chemical in dust
April 20, 2019 - Scientists use NIR light and injected DNA nanodevice to guide stem cells to injury
Roundworm study suggests alternatives for treatment of schizophrenia

Roundworm study suggests alternatives for treatment of schizophrenia

image_pdfDownload PDFimage_print

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