Nav: Home

Newborn Immune Activation May Have Long-Term Negative Impact on Brain FunctionNewborn immune activation may have long-term negative impact on brain function

January 12, 2018

Belmont, MA - McLean Hospital neuroscientists have found that even a brief episode of immune system activation within days of birth can cause persistent changes in sleep patterns concurrent with increases in epilepsy-like brain activity--a combination of symptoms common in autism spectrum disorder (ASD) and other developmental conditions. The detailed findings are available in the January 12, 2018, issue of Neuropsychopharmacology.

"A growing body of evidence suggests that immune system activation, such as that caused by bacterial and viral infections, can play important roles in many brain disorders," explained William Carlezon, PhD, chief of the Division of Basic Neuroscience at McLean Hospital, and senior author of the paper. "While previous research in laboratory animals has established that immune activation during critical prenatal (before birth) developmental periods can later produce the core features of ASD, including decreased social interaction, aberrant communication, and increased repetitive behavior, we wanted to evaluate whether postnatal (during infancy) immune activation could also produce other symptom clusters that are often seen in ASD and related conditions."

In humans, ASD is also frequently associated with certain co-occurring medical conditions, such as sleep disorders and seizures. To determine whether early postnatal immune system activation can produce these types of effects, McLean researchers treated mice with a lipopolysaccharide (LPS), a chemical that simulates a bacterial infection and causes a temporary (1-3 day) activation of the immune system. The LPS was given at a time point in mice (9 days after birth) that approximates the stage of brain development in humans at birth after full-term pregnancy. The mice were then implanted with micro-transmitters that enabled the researchers to collect an uninterrupted stream of data on sleep, muscle movement, and activity levels. Data collection continued through 12 weeks of age, a time point considered to represent adulthood in mice.

Carlezon, who is a professor of psychiatry at Harvard Medical School, and his team discovered that temporary immune system activation shortly after birth produced two main findings in the adult mice. First, immune-activated mice spent more time in slow-wave sleep, a sleep phase often associated with systemic inflammation. Second, the mice also showed dramatic increases in brief (lasting 2-3 seconds) bouts of abnormal brain wave activity. These events had the hallmark characteristics of spike-wave discharges (SWDs), a type of epilepsy-like brain activity that is not accompanied by full-body seizures. Although the SWDs occurred throughout the day, they were much more prevalent during periods when the mice were sleeping. When they occurred during wakefulness, they were accompanied by complete behavioral arrest--a period of no movement throughout the body--and immediately followed by recovery of normal brain activity and movement. Collectively, these findings demonstrate that even a brief period of immune system activation during critical periods of early development can leave a long-term signature upon the brain.

"The fact that immune system activation can produce these effects on its own, without any type of accompanying injury or trauma, provides new insight on the many paths that can lead to abnormal brain function" said Carlezon. "While there are clearly other factors that can cause these types of abnormalities, including genetic vulnerabilities, demonstrating that immune activation alone can produce these effects offers new hope for treatments that might reduce their severity, or prevent them altogether, in certain individuals."

While Carlezon's research focuses on animal models, his findings have implications for humans. The researchers believe that studying early developmental immune activation in mice may be valuable for diagnosing certain human illnesses and understanding how they develop. Persistent alterations in slow-wave sleep may represent a biomarker that could help differentiate immune-related neuropsychiatric conditions from those with other causes. Meanwhile, understanding epilepsy-like brain activity during both sleep and wakefulness may be useful in developing improved models of ASD. Studies in humans have shown that up to 60% of individuals with ASD experience SWDs during sleep, despite no diagnosis of clinical epilepsy, suggesting accuracy of the mouse model. The SWDs during wakefulness may resemble conditions such as "absence seizures" in humans, which are characterized by a brief loss of consciousness, a blank stare, and cessation of movement, and are often confused with inattention or intellectual disability.

"While more research needs to be conducted, these findings are a significant step forward in unlocking the mystery of ASD and other developmental disorders," said Carlezon.
McLean Hospital is the largest psychiatric affiliate of Harvard Medical School and a member of Partners HealthCare. In 2017, it was named the #1 hospital for psychiatric care in the United States by U.S. News & World Report. For more information about McLean, visit or follow the hospital on Facebook or Twitter.

McLean Hospital

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

How the Immune System Works (The How it Works Series)
by Lauren M. Sompayrac (Author)

How the Immune System Works has helped thousands of students understand what’s in their big, thick, immunology textbooks. In his book, Dr. Sompayrac cuts through the jargon and details to reveal, in simple language, the essence of this complex subject.

In fifteen easy-to-read chapters, featuring the humorous style and engaging analogies developed by Dr. Sompayrac, How the Immune System Works explains how the immune system players work together to protect us from disease – and, most importantly, why they do it this way.

Rigorously updated for this fifth... View Details

The Immune System, 4th Edition
by Peter Parham (Author)

The Immune System, Fourth Edition emphasizes the human immune system and presents immunological concepts in a coherent, concise, and contemporary account of how the immune system works. Written for undergraduate, medical, veterinary, dental, and pharmacy students, it makes generous use of medical examples to illustrate points. This classroom-proven textbook offers clear writing, full-color illustrations, and section and chapter summaries that make the book accessible and easily understandable to students.

The Fourth Edition is a major revision that brings the content... View Details

The Immune System Recovery Plan: A Doctor's 4-Step Program to Treat Autoimmune Disease
by Susan Blum (Author), Mark Hyman (Foreword), Michele Bender (Foreword)

One of the most sought-after experts in the field of functional medicine shares her proven four-step program to treat, reverse, and prevent autoimmune conditions and repair your immune system.

• Are you constantly exhausted?

• Do you frequently feel sick?

• Are you hot when others are cold, or cold when everyone else is warm?

• Do you have trouble thinking clearly, aka “brain fog”?

• Do you often feel irritable?

• Are you experiencing hair loss, dry skin, or unexplained weight fluctuation?

• Do your joints ache or... View Details

The Immune System: A Very Short Introduction (Very Short Introductions)
by Paul Klenerman (Author)

The immune system is central to human health and the focus of much medical research. Growing understanding of the immune system, and especially the creation of immune memory (long lasting protection), which can be harnessed in the design of vaccines, have been major breakthroughs in medicine.

In this Very Short Introduction, Paul Klenerman describes the immune system, and how it works in health and disease. In particular he focuses on the human immune system, considering how it evolved, the basic rules that govern its behavior, and the major health threats where it is... View Details

Basic Immunology: Functions and Disorders of the Immune System, 5e
by Abul K. Abbas MBBS (Author), Andrew H. H. Lichtman MD PhD (Author), Shiv Pillai MBBS PhD (Author)

In this updated edition of Basic Immunology, the authors continue to deliver a clear, modern introduction to immunology, making this the obvious choice for today's busy students. Their experience as teachers, course directors, and lecturers helps them to distill the core information required to understand this complex field. Through the use of high-quality illustrations, relevant clinical cases, and concise, focused text, it's a perfectly accessible introduction to the workings of the human immune system, with an emphasis on clinical relevance.... View Details

The Immune System, 3rd Edition
by Peter Parham (Author)

The Immune System, Third Edition emphasizes the human immune system and synthesizes immunological concepts into a comprehensible, up-to-date, and reader-friendly account of how the immune system works. 

Written for undergraduate, medical, veterinary, dental, and pharmacy students in immunology courses, it makes generous use of medical examples to illustrate points. 

The Third Edition has been extensively revised and updated and includes two new chapters on innate and adaptive immunity, which explore the physical, cellular, and molecular principles... View Details

Immune System: 101 Natural Ways to Boost your Immune System, Fight Germs, and Live a Healthy Life
by Living in Health (Author)

BOOST YOUR IMMUNE SYSTEM! 101 NATURAL WAYS TO BOOST YOUR IMMUNE SYSTEM, FIGHT GERMS, AND LIVE A HEALTHY LIFE Your immune system is the body’s only line of defense against both foreign and internal threats. It is clear therefore that you must maintain your immune system in the best possible condition for optimal health. It is not a myth that some foods are better than others at boosting our immunity. If you were ever wondering what might be the best foods in the world to help keep your immune system in the best shape, then this book is simply the way to go. It really helps to have a great... View Details

Immune: How Your Body Defends and Protects You (Bloomsbury Sigma)
by Catherine Carver (Author)

The human body is like an exceedingly well-fortified castle, defended by billions of soldiers--some live for less than a day, others remember battles for decades, but all are essential in protecting us from disease. This hidden army is our immune system, and without it we could not survive the eternal war between us and our microscopic enemies.

Immune explores the incredible arsenal that lives within us--how it knows what to attack and what to defend, and how it kills everything from the common cold to the plague bacterium. We see what happens when the immune system turns on... View Details

The Immune System (The Human Body: How It Works)
by Gregory J. Stewart (Author), Denton A., M.D. Cooley (Introduction)

Discusses the immune system; including the cells, tissues, and organs involved in its function; and explains its role in keeping the body free from illness and disease. View Details

The Little Soldiers in the Body - Immune System - Biology Book for Kids | Children's Biology Books
by Baby Professor (Author)

Do you know what’s the best way to explain biology to kids? You use storytelling. You use characters that would attract the attention and active participation of a child’s imagination. It is by these that a child can remember even the littlest details read from informative books like theses. Encourage your child to learn about the immune system. Encourage your child to read this book today! View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Consequences Of Racism
What does it mean to be judged before you walk through the door? What are the consequences? This week, TED speakers delve into the ways racism impacts our lives, from education, to health, to safety. Guests include poet and writer Clint Smith, writer and activist Miriam Zoila Pérez, educator Dena Simmons, and former prosecutor Adam Foss.
Now Playing: Science for the People

#465 How The Nose Knows
We've all got a nose but how does it work? Why do we like some smells and not others, and why can we all agree that some smells are good and some smells are bad, while others are dependant on personal or cultural preferences? We speak with Asifa Majid, Professor of Language, Communication and Cultural Cognition at Radboud University, about the intersection of culture, language, and smell. And we level up on our olfactory neuroscience with University of Pennsylvania Professor Jay Gottfried.