Breaking News
January 18, 2018 - A new strategy proposed for drug discovery
January 17, 2018 - Lactation May Lower T2D Risk in Younger Women
January 17, 2018 - New Atopic Dermatitis Yardstick provides practical guidance and management insights
January 17, 2018 - New biodegradable pressure sensor could help monitor serious health conditions
January 17, 2018 - HSS orders Sectra’s 3D pre-operative planning solution for improving patient outcomes
January 17, 2018 - Study identifies six new genes regions associated with diabetes
January 17, 2018 - Women do not receive timely diagnosis for heart disease
January 17, 2018 - AbbVie’s Upadacitinib Shows Positive Results as Monotherapy in Phase 3 Rheumatoid Arthritis Study, Meeting All Primary and Key Secondary Endpoints
January 17, 2018 - Should President Trump’s Physical Include a Cognitive Screen?
January 17, 2018 - Could gene therapy someday eliminate HIV?
January 17, 2018 - Researchers identify new anti-inflammatory drug target
January 17, 2018 - Loxo Oncology Initiates Rolling Submission of New Drug Application to U.S. Food and Drug Administration for Larotrectinib for the Treatment of TRK Fusion Cancers
January 17, 2018 - Trunk Imaging Tied to Higher Nephrectomy Risk
January 17, 2018 - Campaigners incensed at failings in Africa AIDS war
January 17, 2018 - Research opens door to development of new treatment for type 2 diabetes
January 17, 2018 - Bariatric surgery extends lifespan in obese patients, shows study
January 17, 2018 - Bristol-Myers Squibb Receives FDA Approval for Opdivo (nivolumab) as Adjuvant Therapy in Patients with Completely Resected Melanoma with Lymph Node Involvement or Metastatic Disease
January 17, 2018 - Ewww Moments in the ER: That’s Improbable!
January 17, 2018 - Methods from optogenetics, machine learning should help improve treatment options for stroke patients
January 17, 2018 - Booze may help or harm the heart, but income matters
January 17, 2018 - Three-dimensional organization of genome plays key role in gene expression, cell fate
January 17, 2018 - Scientists identify six new gene regions that may help treat type 1 diabetes
January 17, 2018 - Top nutrients needed to boost mood and energy levels on Blue Monday
January 17, 2018 - Scientists develop unique technique to map elasticity of cell components
January 17, 2018 - Obesity surgery reduces the risk of death by half finds new study
January 17, 2018 - Raw Meat Not the Safest Choice for Your Dog or for You
January 17, 2018 - Men who lack HSD17B4 gene may be more susceptible to treatment-resistant prostate cancer
January 17, 2018 - High-Dose Aspirin Preferred for Kawasaki’s
January 17, 2018 - Study suggests risk management approach to combat EMS fatigue
January 17, 2018 - A new therapy against obesity
January 17, 2018 - Doctors warn against holding your nose and closing your mouth to contain a sneeze
January 17, 2018 - Measles outbreak alarms public health officials
January 17, 2018 - FDA Slaps Class Warning on Gadolinium Contrast Agents
January 17, 2018 - Distinct human mutations can alter the effect of medicine
January 17, 2018 - ASIT biotech’s new article presents clinical results of gp
January 17, 2018 - Alternative tobacco use by adolescents associated with greater odds of future cigarette smoking
January 17, 2018 - A High-Salt Diet Produces Dementia In Mice
January 17, 2018 - Scientists provide insights into crucial interaction for DNA repair
January 17, 2018 - Sanofi and Regeneron Announce Positive Topline Pivotal Results for PD-1 Antibody Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma
January 17, 2018 - Morning Break: Pfizer Kills AD/PD Pipeline; Trump Affirms His Mental Health; Humira Pricing Strategy
January 17, 2018 - Researchers see gene influencing performance of sleep-deprived people
January 17, 2018 - Fast food triggers the immune system making it hyperactive
January 17, 2018 - Scientists find increased risk of HIV outbreaks in Ukraine due to war-related migration
January 17, 2018 - New universal flu vaccine moves to clinical trial phase and could be a reality soon
January 17, 2018 - Cocaine de-addiction breakthrough shows promise
January 17, 2018 - FDA Accepts New Drug Application for Seysara (sarecycline) for the Treatment of Moderate to Severe Acne
January 17, 2018 - Robotic Telestenting; BP Cuff Smartwatch; Medicare Bundled Care
January 17, 2018 - New cellular approach found to control progression of chronic kidney disease
January 17, 2018 - Lamprey genes provide clues to repair spinal cord damage, finds study
January 17, 2018 - Tissue-based soft robot could lead to advances in bio-inspired robotics
January 17, 2018 - Mostly the healthy and wealthy Americans use mobile phone apps to track sleep habits
January 17, 2018 - FDA Alert: Varubi (rolapitant) Injectable Emulsion: Health Care Provider Letter
January 16, 2018 - NeuroBreak: Rough Days for Neuroscience Research; Another Migraine Drug Advances
January 16, 2018 - The ‘greatest pandemic in history’ was 100 years ago – but many of us still get the basic facts wrong
January 16, 2018 - Serena Williams Shares Childbirth Ordeal
January 16, 2018 - The Artificial Brain as Doctor
January 16, 2018 - Type 2 diabetes has hepatic origins
January 16, 2018 - Expert discusses how to identify, support individuals with drug or alcohol addiction in workplace
January 16, 2018 - Starting menstruation early increases risk of cardiovascular disease and stroke in later life
January 16, 2018 - CapsoVision receives CE Mark approval for use of CapsoCam Plus System in pediatric patients
January 16, 2018 - Researchers develop new dynamic statistical model to follow gene expressions over time
January 16, 2018 - Alzheimer’s ‘looks like me, it looks like you’
January 16, 2018 - By the Numbers: Physicians’ Economic Impact
January 16, 2018 - Sound Health | NIH News in Health
January 16, 2018 - Modifying baby formula doesn’t prevent type 1 diabetes in children
January 16, 2018 - Energy drinks dangerous for kids
January 16, 2018 - When you need a breast screening, should you get a 3-D mammogram?
January 16, 2018 - Johns Hopkins gets approval to perform HIV positive to HIV positive living donor kidney transplants
January 16, 2018 - The Salk Institute and Indivumed collaborate for cutting-edge cancer research
January 16, 2018 - Study reveals negative long-term effects of heavy cannabis use on brain function and behavior
January 16, 2018 - Many gym-goers injure themselves by pushing harder to be better than friends
January 16, 2018 - Risankizumab Meets All Primary Endpoints Reporting Positive Results in Fourth Pivotal Phase 3 Psoriasis Study
January 16, 2018 - Federal Junk Food Tax Feasible, Study Says
January 16, 2018 - Do girls have stronger teeth than boys?
January 16, 2018 - New high-sensitivity blood tests could aid faster diagnosis and treatment for heart attack
January 16, 2018 - How fatal mitochondrial diseases may strike offspring of families with no history of the conditions
January 16, 2018 - TherapeuticsMD Announces FDA Acceptance of New Drug Application and Prescription Drug User Fee Act (PDUFA) Date for TX-004HR
January 16, 2018 - Morning Break: Food Pharmacies; Obamacare Sign-ups Dip; Top Pot Studies
January 16, 2018 - Blood pressure declines 14 to 18 years before death
January 16, 2018 - ViLim Ball technology helps reduce uncontrollable shaking hands
In autism, too many brain connections may be at root of condition

In autism, too many brain connections may be at root of condition

image_pdfDownload PDFimage_print
Credit: CC0 Public Domain

A defective gene linked to autism influences how neurons connect and communicate with each other in the brain, according to a study from Washington University School of Medicine in St. Louis. Rodents that lack the gene form too many connections between brain neurons and have difficulty learning.

The findings, published Nov. 2 in Nature Communications, suggest that some of the diverse symptoms of autism may stem from a malfunction in communication among cells in the brain.

“This study raises the possibility that there may be too many synapses in the brains of patients with autism,” said senior author Azad Bonni, MD, PhD, the Edison Professor of Neuroscience and head of the Department of Neuroscience at Washington University School of Medicine in St. Louis. “You might think that having more synapses would make the brain work better, but that doesn’t seem to be the case. An increased number of synapses creates miscommunication among neurons in the developing brain that correlates with impairments in learning, although we don’t know how.”

Autism is a neurodevelopmental disorder affecting about one out of every 68 children. It is characterized by social and communication challenges.

Among the many genes linked to autism in people are six genes that attach a molecular tag, called ubiquitin, to proteins. These genes, called ubiquitin ligases, function like a work order, telling the rest of the cell how to deal with the tagged proteins: This one should be discarded, that one should be rerouted to another part of the cell, a third needs to have its activity dialed up or down.

Patients with autism may carry a mutation that prevents one of their ubiquitin genes from working properly. But how problems with tagging proteins affect how the brain is hardwired and operates, and why such problems may lead to autism, has remained poorly understood.

To understand the role of ubiquitin genes in brain development, Bonni, first author Pamela Valnegri, PhD, and colleagues removed the ubiquitin gene RNF8 in neurons in the cerebellum of young mice. The cerebellum is one of the key brain regions affected by autism.

The researchers found that neurons that lacked the RNF8 protein formed about 50 percent more synapses – the connections that allow neurons to send signals from one to another – than those with the gene. And the extra synapses worked. By measuring the electrical signal in the receiving cells, the researchers found that the strength of the signal was doubled in the mice that lacked the protein.

The cerebellum is indispensable for movement and learning motor skills such as how to ride a bicycle. Some of the recognizable symptoms of autism – such as motor incoordination and a tendency to walk tippy-toed – involve control of movement.

The animals missing the RNF8 gene in the neurons of their cerebellum did not have any obvious problems with movement: They walked normally and appeared coordinated. When the researchers tested their ability to learn motor skills, however, the mice without RNF8 failed miserably.

The researchers trained the mice to associate a quick puff of air to the eye with the blinking of a light. Most mice learn to shut their eyes when they see the light blink, to avoid the irritation of the coming air puff. After a week of training, mice with a functioning copy of the gene closed their eyes in anticipation more than three quarters of the time, while mice without the gene shut their eyes just a third of the time.

While it is best known for its role in movement, the cerebellum is also important in higher cognitive functions such as language and attention, both of which are affected in autism. People with autism often have language delays and pay unusually intense attention to objects or topics that interest them. The cerebellum may be involved not only in motor learning but in other features of autism as well, the researchers said.

Of course, there is a world of difference between a mouse that can’t learn to shut its eyes and a person with autism who struggles to communicate. But the researchers said the findings suggest that changing how many connections neurons make with each other can have important implications for behavior.

Since this paper was written, Bonni and colleagues have tested the other autism-associated ubiquitin genes. Inhibition of all genes tested cause an increase in the number of synapses in the cerebellum.

“It’s possible that excessive connections between neurons contribute to autism,” Bonni said. “More work needs to be done to verify this hypothesis in people, but if that turns out to be true, then you can start looking at ways of controlling the number of synapses. It could potentially benefit not just people who have these rare mutations in ubiquitin genes but other patients with autism.”


Explore further:
Autism treatments may restore brain connections

More information:
Pamela Valnegri et al, RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain, Nature Communications (2017). DOI: 10.1038/s41467-017-01333-6

Journal reference:
Nature Communications

Provided by:
Washington University School of Medicine

Tagged with:

About author

Related Articles