How do we study the brain?
Autism is a clinically diagnosed disorder. Much of our knowledge about autism comes from direct interactions with people diagnosed with autism spectrum disorders (ASD), listening to parents of children on the spectrum, and conducting clinical studies. Magnetic Resonance imaging (MRI) studies have added to our understanding by giving us a peek at the autistic brain and structural differences that may be present. Additionally, strong efforts in genetic analysis have discovered genes of interest and regions within our DNA that may play a part in the development of ASD. Though all these efforts have taught us much about autism, we still know relatively little about the autistic brain and why its development is altered. So how do we learn more?
We must look at things directly.
Consider the following analogy. If you were told to study an office building, but could not go inside, you may find yourself walking around the structure and studying its shape. You could interact with the building by touching the stone and steel that form the building. This would be analogous to clinical and behavioral observations typically made of individuals with autism. Engineering plans, may tell you what the building is comprised of (analogous to genetics studies) and even how it is shaped on the inside—where the rooms are and how stairs, elevators and hallways connect them. This last approach would be analogous to structural MRI studies. Despite the value of each of these perspectives, none of these examinations could reveal the happenings within the building. You would know nothing about the people working within the building, what they were doing, how they interacted with each other and what their jobs may have been.
In a similar way this is how we most often study autism, by looking at the outside, taking an indirect perspective. But there are some scientists who look at things differently. They go inside the building. They study brains directly. And what some of these exceptional scientists have learned so far is quite astounding.
Studying brain tissue directly from deceased individuals, enables researchers to look microscopically at the cells within human brains, how these cells are connected with one another, how they are structured on a molecular level and what that most interesting of molecules – DNA – is doing within the cell. Studying the brain directly allows a far more thorough level of research to be conducted; enabling researches to ask and answer questions that otherwise could not have been addressed, to study the cell and molecular bases behind autism, and granting the ability to look at the fundamental underpinnings behind ASD. Scientists need to study brains from both affected and unaffected individuals in order to make informative comparisons. Without both affected and unaffected individuals to study, the brain tissue loses context and is far less instructive.
Recent breakthroughs in brain tissue research
With brain tissue, scientists can look at the many components needed to make and organize proteins within a cell for proper brain function. Investigators have explored genes that synthesize a major inhibitory transmitter (GABA) in the neural cells and found decreased activity in a special type of protein called an enzyme. In addition, other molecules that detect and bind to GABA (called receptors) are decreased in prevalence in several brain regions. Enzymes and receptors are targets for therapeutics (drug intervention) and are therefore important to understand.
A report investigating 26 brains from the Brain Atlas Project describes some of the atypical findings in the brains of individuals with autism: namely defects in the production, development and organization of new neurons in the brain. Using digital images available to researchers from the Brain Atlas Project, investigators showed that cell populations in the brain, organized in distinct patterns termed minicolumns, are more numerous in the autism brains. Scientists postulate that this increase of minicolumns results in higher sensitivity to stimuli coming into the brain, but at a cost to processing and output in the form of behaviors that characterize autism.
Brain tissue evaluation of mitochrondria reveals differences in these critical cell powerhouses. Mitochondria are responsible for producing most of the energy inside a cell. Brain tissue research has revealed defects in mitochondrial proteins important for shuttling molecules across brain cell membranes. Much like a battery, controlling the flow of molecules within different compartments of a cell is one of the key components to the energy production process and one that appears to be functioning differently in individuals with autism.
Oxytocin is a hormone with a role in social recognition, pair bonding, anxiety, and maternal behaviors. Brain tissue research provides evidence of oxytocin receptor deficiencies resulting in a lower level of effectiveness. This means that even if the hormone is produced normally, it has a reduced effect. Treatments to increase oxytocin functionality in the brain are being explored and brain research will continue to contribute to the understanding of the role of this hormone in the brain.
Scientists also use brain tissue to explore findings from other medical assessments. Analysis of cerebral spinal fluid (CSF) from subjects with autism has shown immune markers of neuroinflammation. Immune activity found in cells from the brain support the concept that specialized brain cells that respond to infection or damage are active in autism brain samples.
How you can help
Unfortunately, brain tissue is exceptionally rare, thereby hindering this rigorous approach to understating autism
The Autism Tissue Program (ATP), a clinical program of Autism Speaks, is dedicated to supporting scientists worldwide in their efforts to understand autism, autism related disorders and the human brain. The ATP makes brain tissue available to as many qualified scientists as possible to advance autism research and unravel the mysteries of this and related neurological conditions. In fact, it is the only program solely dedicated to increasing and enhancing the availability of post-mortem brain tissue for basic research in autism. You can make a profound difference to all those who struggle with autism by registering as a brain tissue donor with the ATP.
A large part about why we, at the ATP, keep working is that when people with autism die, it is sometimes unexpectedly and with little to explain the cause of death. Detailed analysis of the donated tissue helps provide answers as to why death occurred and helps us learn more about these unique individuals in addition to helping researchers understand autism.
If you are the parent of a child or children with an autism spectrum disorder, are related to a person with an autism spectrum disorder, have autism yourself or are unaffected, your donation can greatly affect our progress in understanding autism. We encourage entire families to consider donations of brain tissue for research.
While in some states and countries, registration for organ donation makes the process automatic at the time of death (as on your driver’s license), this is not the case for brain tissue donation. Because brain tissue is used for research and not transplantation, it is not included on most organ donation registries. Therefore, by registering with the ATP, you declare your intent to donate brain tissue as well as making your wishes known to your family in a formalized way. However, registration does not make tissue donation automatic at the time death. This final choice of donation is made by your next-of-kin, which in legal terms, is defined in this order: spouse, adult children, either parent, adult siblings, or guardian at the time of death. Should you choose to become an ATP registrant, and wish to donate your brain upon death, to the ATP in support of autism research, we encourage you to inform others of your wishes, including your immediate and extended family. Helping your friends and family learn more about the ATP and its mission will help them understand your unique choice.
For more information about the ATP and becoming a registered donor, visit our site at www.autismtissue program.org.