Breaking News
December 11, 2018 - AHA: 12-Year-Old Heart Defect Survivor Inspires NFL Player’s Foundation
December 11, 2018 - Breast cancer patients who take heart drug with trastuzumab have less heart damage
December 11, 2018 - Providing aid to those humans – and animals – affected by the California fires
December 11, 2018 - Even without proof, CBD is finding a niche as a cure-all
December 11, 2018 - Drawing leads to better memory than writing
December 11, 2018 - Researchers report novel findings on plant hormone
December 10, 2018 - A Tale of Two Labels
December 10, 2018 - Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model
December 10, 2018 - A 14-year-old explains what it’s like to get a new heart
December 10, 2018 - Team Players Honored with 2018 Baton Awards
December 10, 2018 - Global report highlights how the changing world is affecting children’s physical activity levels
December 10, 2018 - Genes play a role in physical activity and sleep
December 10, 2018 - DDT in Alaskan fish shown to increase risk of cancer
December 10, 2018 - Laws to curb use of cell phones have greatly reduced fatalities for motorcyclists
December 10, 2018 - Argenx Provides Detailed Data from Phase 2 Clinical Trial of Efgartigimod in Immune Thrombocytopenia and Phase 1/2 Clinical Trial of Cusatuzumab in Acute Myeloid Leukemia
December 10, 2018 - University of Maryland doctors treat first breast cancer patients with GammaPod radiotherapy
December 10, 2018 - The heartbeat seat: Demoing new well-being technologies in a car
December 10, 2018 - Leading Cancer Researcher to Direct Herbert Irving Comprehensive Cancer Center
December 10, 2018 - Study compares pain-related diagnoses in First Nations and non-First Nations children, youth
December 10, 2018 - Experts address sleep disorders following traumatic brain injury
December 10, 2018 - Scientists find answers to how cancer spreads
December 10, 2018 - Study explores why older people read more slowly
December 10, 2018 - Smart life-collar could save lives of young children
December 10, 2018 - Asbestos found in most NHS hospitals finds BBC inquiry
December 10, 2018 - Researchers use new technique to probe hydrogen bonds
December 10, 2018 - Music improves social communication in autistic children
December 10, 2018 - Some Brain Tumors May Respond to Immunotherapy, New Study Suggests
December 10, 2018 - Banning junk food ads to combat childhood obesity
December 10, 2018 - Skin Autofluorescence Predicts T2DM, Heart Disease, Mortality
December 10, 2018 - Largest autism sequencing study to date yields 102 genes associated with ASD
December 10, 2018 - Statins associated with low risk of side effects
December 10, 2018 - Episodic memory tests help in predicting brain atrophy and Alzheimer’s disease
December 10, 2018 - Study explores how schools address adolescent self-harming practices
December 10, 2018 - Pregnancy in adolescence linked to increased risks of complications in young mothers
December 10, 2018 - Risk Analysis publishes special issue on communicating about Zika virus
December 10, 2018 - Botox May Help Prevent Post-Op A-Fib
December 10, 2018 - African-American mothers rate boys higher for ADHD
December 10, 2018 - Graphic warning labels cancel out cigarettes’ appeal to young people
December 10, 2018 - Australian researchers to study gas inhalational anaesthetic and likelihood of cancer return
December 10, 2018 - Individual neurons located within the brain have implications for psychiatric diseases
December 10, 2018 - Researchers improve bariatric surgery scoring system to extend prediction time for diabetic remission
December 10, 2018 - HPV type 16 or 18 associated with cervical cancer risk in young women
December 10, 2018 - Cervical cancer risk is higher in women with positive HPV, but no cellular abnormalities
December 10, 2018 - Combo therapy not needed if low RA disease activity achieved
December 10, 2018 - Novel therapeutic targets based on biology of aging show promise for Alzheimer’s disease
December 10, 2018 - UC San Diego professor receives NCI Outstanding Investigator Award for cancer research
December 10, 2018 - Study evaluates placental mesenchymal stem cell sheets for myocardial repair and regeneration
December 10, 2018 - Blueprint Medicines Announces Updated Results from Ongoing EXPLORER Clinical Trial of Avapritinib Demonstrating Broad Clinical Activity and Significant Symptom Reductions in Patients with Systemic Mastocytosis
December 10, 2018 - Study clarifies ApoE4’s role in dementia
December 10, 2018 - Eating disorders now a top priority with Australian Government
December 10, 2018 - Neuronal activity in the brain allows prediction of risky or safe decisions
December 10, 2018 - FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy
December 10, 2018 - Improving dementia care and treatment saves thousands of pounds in care homes
December 10, 2018 - Heroin-assisted treatment can offer benefits, reduce harms
December 10, 2018 - People covered by Michigan’s expanded Medicaid program report improvements in health, finds study
December 10, 2018 - Hazelnuts improve micronutrient levels in older adults
December 9, 2018 - History of Partner Violence Tied to Menopause Symptoms
December 9, 2018 - Clean Up Safely After a Disaster|Natural Disasters and Severe Weather
December 9, 2018 - Drug wholesalers drove fentanyl’s deadly rise, report concludes
December 9, 2018 - Deprescribing could help manage polypharmacy in older adults
December 9, 2018 - Retraction of article “Joy of cooking too much” from journal
December 9, 2018 - FDA Warns of Rare Stroke Risk With MS Drug Lemtrada (Alemtuzumab)
December 9, 2018 - Feds say heroin, fentanyl remain biggest drug threat to US
December 9, 2018 - Eliminating microglia can reverse some aspects of stress sensitization, study shows
December 9, 2018 - New genetic insight could help treat rare debilitating heart and lung condition
December 9, 2018 - MiRagen Therapeutics Announces Final Safety, Biodistribution and Clinical Efficacy Data From Phase 1 Cobomarsen Clinical Trial in Patients With Mycosis Fungoides
December 9, 2018 - Work with your doctor to weigh pros, cons of treatment options for hyperthyroidism
December 9, 2018 - CWRU researcher secures $14.6 million funding for genetic study into Alzheimer’s disease
December 9, 2018 - High intensity statin treatment and adherence could save more lives
December 9, 2018 - Surgery patients use only 1/4 of prescribed opioids, and prescription size matters
December 9, 2018 - AXT offers Phi Optics upgrade to QPI systems for inverted light microscopes
December 9, 2018 - New booklet could help improve conditions of young pupils with albinism
December 9, 2018 - Few Physicians Work in Practices That Use Telemedicine
December 9, 2018 - Older Adults and Oral Health
December 9, 2018 - Health utility values improve after septorhinoplasty
December 9, 2018 - New EU-funded project provides insight into how the brain develops
December 9, 2018 - Expanded use of tele-emergency services can help strengthen rural hospitals
December 9, 2018 - Infections in the Young May Be Tied to Risk for Mental Illness: Study
December 9, 2018 - Profile: Native Hawaiians and Pacific Islanders
December 9, 2018 - Snoring poses greater cardiac risk to women
Scientists alleviate schizophrenic symptoms in mice

Scientists alleviate schizophrenic symptoms in mice

image_pdfDownload PDFimage_print

Despite extensive research efforts, schizophrenia remains one of the least understood brain disorders. One promising area of research is in receptors on the surfaces of brain cells that help sense growth factors. But there’s been a problem: in previous schizophrenia studies, researchers have genetically manipulated brain cell receptors in very young mice. Schizophrenia usually affects adults.

In a recent issue of the Proceedings of the National Academy of Sciences, Lin Mei, MD, PhD, asked, does all the tinkering in young mice hamper their brain development, causing schizophrenia-like symptoms? Or, do their brain cells develop normally, but in adulthood struggle to communicate? Researchers need to know whether to focus their efforts on brain cell development or communication, or both, because the answer to these questions implies different therapeutic approaches.

In the new study, Mei, professor and chair of neurosciences at Case Western Reserve University School of Medicine, led an international team of neuroscientists. The team included Mei’s long-time collaborator, Wen-Cheng Xiong, PhD, professor of neurosciences, and first authors Hongsheng Wang and Wenbing Chen, graduate students, all of CWRU. Additional collaborators included researchers at Nanchang University and Guangzhou Medical University in China, and neuroscientists from the Medical College of Georgia at Augusta University.

Together, the researchers studied a brain cell receptor–ErbB4–whose level is altered in adults with schizophrenia. ErbB4 helps maintain an inhibitory neurotransmitter in the brain–GABA–that prevents brain cells from overreacting and keeps fear and anxiety in check. The researchers have shown previously that ErbB4 mutations change signals inside brain cells that lead to schizophrenic symptoms in mice.

“When ErbB4 is mutated early on in mice, it impairs brain circuit wiring. It also impairs GABA transmission in adult animals, causing schizophrenic symptoms,” said Mei. “But previous models are unable to distinguish whether deficits are from abnormal development in young mice brains, or abnormal transmission developed later on.” Mei’s new study shows schizophrenic symptoms come from deficits in how brain cells communicate during adulthood, regardless of whether or not they fully developed.

To find their answers, Mei’s team genetically engineered two new mouse models of schizophrenia. In the first, the researchers treated mice with a chemical that switches “off” the gene encoding ErbB4. “Using inducible knock-out mice, we depleted ErbB4 only in adult animals, and showed that this impairs behavior,” said Mei. In mice missing ErbB4 only in adulthood, brain cell development and appearance were normal, but symptoms persisted. The experiment suggested schizophrenic symptoms in adult mice were unrelated to abnormal brain cell development.

In the second mouse model, the receptor was missing in mice from the beginning, hampering brain cell development. The researchers used the same genetic switch to turn ErbB4 “on” in adulthood–in essence, recovering it. “In recovery knock-out mice, ErbB4 is missing during development and thus the mice have crippled brain circuits. Yet, when ErbB4 is restored on a malformed circuit, mice scored better in behavioral tests,” said Mei. Even with underdeveloped brain cells, schizophrenic symptoms could be alleviated simply by adding ErbB4.

Mei’s team found restoring ErbB4 receptors reduced hyperactivity, and normalized fear responses in adult mice. “ErbB4 is a risk factor for schizophrenia,” said Mei. “This study shows correcting ErbB4 signaling could be therapeutic in relevant patients.”

The results in the two mouse models confirm that ErbB4 is critical to how brain cells communicate during adulthood. The nuanced distinction could lead to new therapeutics designed to improve brain cell signaling associated with the ErbB4 receptor. In particular, therapeutics that improve how GABA neurotransmitters regulate brain cell activity.

“Restoring ErbB4 could be beneficial to patients–even those with malformed brain circuitry,” said Mei. “We are now looking into how restoring ErbB4 improves neurotransmitter signaling inside brain cells, including those relevant to other psychiatric disorders, such as attention deficit hyperactivity disorder and major depression.”

Source:

http://casemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=1575&news_category=8

Tagged with:

About author

Related Articles