'Mutant ferrets' shine a light on human brain evolution

In the past 7 million years human brain size has tripled.  Recently a group of researchers from several different institutions have began studies looking at microcephaly. Microcephaly is the "abnormal smallness of the head, a congenital condition associated with incomplete brain development." It is often genetic and has recently been linked to the Zika virus. There is little known about how and why the incomplete brain development occurs. This is due to the fact that there has not been a good model to explore these questions.

The gene involved in microcephaly codes for a protein called Aspm. When the gene is mutated it results in a humans brain being half the size of what is normal. Mice could not be a model for this study because when mutating the gene their brains only decrease by one tenth, which is not comparable with the effects it has on humans. The researchers then tried using ferrets as a model.

With Aspm knockout ferrets' it resulted in their brain size decreasing by 40 percent. This result was much closer to how humans are affected and the results were able to be compared for further questions. Such as back to the main question, why do humans have such large brains. They found that when Aspm is not present it results in the radial glial cells to detach from the ventricles more readily and then they migrated early. Because of this the timing changed and lead to fewer nerve cells in the cortex. Since Aspm regulates the number of cortical neurons it alters brain development by not allowing centrioles to do their job in cell division.

The result of altering this gene is that the "radial glial cells' migration can be altered and the cortex can grow larger." The results from these studies are that they discovered a new model organism for microcephaly, ferrets. As well as that it provided insight into the origin of the brain bulging. In my opinion these findings are important. Now they can find more answers to questions other researchers may have about microcephaly. Before there were many unanswered questions regarding the disorder because of the lack of a model. Finding out more about disorders that cause incomplete brain development could possibly come from using ferrets as models, since the effects they had were very similar to those of humans. This study was interesting and showed the importance of taking the time to find a good model for scientific studies.

Link to Article:
https://www.medicalnewstoday.com/articles/321488.php
Link to more information
https://www.nature.com/articles/s41586-018-0035-0
https://www.medicalnewstoday.com/articles/305880.php

OCD-like Behavior Linked to Gene Mutation in the Brain

Honor Whiteman, a writer for Medical News Today, states that "Researchers have provided further evidence of how gene mutations in a certain brain region might fuel behaviors associated with obsessive-compulsive disorder."

OCD is a disorder where the affected have uncontrollable thoughts, obsessions, and/or compulsions. These thoughts can trigger a persons anxiety which makes it difficult for the person to live their daily lives. The compulsions refer to physical urges that are used to respond to the obsessions, some examples of common OCD include excessive cleaning (hands, clothes, etc.), rearranging items in a particular way, or compulsive counting counting. One percent of adults are affected by this disorder, however within that one percent, 50 percent of individuals severely suffer from OCD. The main causes of this disease are unknown, however, previous studies have show that it may be caused by specific gene mutations in the brain. A new study conducted by researchers from Northwestern University found that certain gene mutations in the corticostriatal region of the brain led to OCD symptoms in mice. This region of the brain is responsible for the regulation in repeating behavior. KAR (kainate receptors) genes play a key role in how the corticostriatal region is developed, and when KAR genes were erased in mice they showed numerous OCD-like behaviors.

I believe that the research done on OCD will prove its worth and help the people suffering from the disease. With the discoveries made by the research team at Northwestern, these KAR genes may be a major cause of OCD. With further studies on these genes and the region of the brain that they are located, doctors and scientist could develop treatments or medications in the very near future.

http://www.medicalnewstoday.com/articles/316039.php
https://news.northwestern.edu/stories/2017/february/ocd-like-behavior-linked-to-genetic-mutation/

Alcohols Impact On the Adolescent Brain

According to a new study at the University of Illinois at Chicago College of Medicine suggests that on and off exposure to alcohol during adolescence can alter the activity of genes for normal brain development. According to the researchers this type of behavior increases anxiety and preference for alcohol in adulthood. This happens epigenetically when alcohol modifies the histones which could change how tightly or loosely wound DNA becomes.During this study the researchers used rats to gather their data. This study also discovered that a drug called HDAC2 could reverse these effects.

In my opinion there should be more research done on this due to the amount of alcohol drank by adolescents. I also do not believe that these findings are concrete evidence of behavior changes. For all we know humans could metabolize alcohol completely differently then rats. Our brain structure could also develop much differently than that of mice. Then again I am in no way shape or form an expert on this topic. However more funding should definitely go towards research like this.

http://www.medicalnewstoday.com/releases/292055.php

Human DNA Placed Into Mouse Embryos

Evolution of the human brain has always been a topic of interest for scientists over the years. Many have wondered how human brains have become so complex and why chimpanzee brains have lagged behind even though chimpanzees have almost all of the same genes that humans have. Scientists at Duke University have tackled this question and obtained some interesting results. More specifically, these scientists have found differences between chimpanzee and human genetic codes and observed how these differences affected embryonic brain development in mice.

For the study scientists focused on shorts pieces of DNA called enhancers that are a part of every genome. These enhancers regulate gene activity and are sometimes human specific. Until now none of these human specific enhancers had been shown to influence brain development directly.  The scientists searched through chimpanzee and human genomes to find enhancers that are expressed in brain tissue and early in development. Enhancers that were largely different between the two species were of high importance. In the beginning, 106 enhancers were narrowed down as being potentially important for discovering the differences in chimp and human brains. Out of these 106, 6 were thought to be involved in brain development. The enhancers were named HARE1-6, standing for human accelerated regulatory enhancers.  HARE5 showed the most promise as it is located near a gene, Frizzled8, which is known for its role in brain development and disease. The researchers directed their attention onto this enhancer and postulated that it enhanced Frizzled8 since HARE5 and Frizzled8 make contact in the brain.  

The HARE5 in humans and chimpanzees only differ by only 16 base pairs. However, the human enhancer was active earlier and more active in general in the mouse embryos than the chimpanzee enhancer. The activity differences between the two enhancers were detected at a critical time in brain development. The mouse embryos with the human HARE5 ultimately ended up with more neurons than those with the chimpanzee HARE5. As the mouse embryos developed more and more and came closer to the end of gestation the difference in size of the brains became noticeable. The mice that had human HARE5 had brains that were 12% larger in area than those that had the chimpanzee HARE5. The part of the brain that was affected was the neocortex. This part of the brain is involved in language and reasoning. 

This feat was astonishing, just narrowing down the enhancers in itself was a difficult and cumbersome task. Many other scientists have tried to do what the Duke University researchers did and failed. As a result of this successful study, a genetic reason as to why humans have bigger brains than chimpanzees has been discovered.

I feel that this is so interesting and awesome that it has finally been discovered. Humans are so closely related to primates, yet so different. It is interesting to realize that all of the differences are most likely due to some small change in the genetic code. I mean if just one different enhancer could make mice brains larger then imagine what a few differences could amount to. It is astonishing to think about the complexity of genes and how they work together to produce many different characteristics. 

Link to Article: http://www.sciencedaily.com/releases/2015/02/150219133104.htm

Additional Link: http://www.latimes.com/science/sciencenow/la-sci-sn-dna-chimp-human-brains-20150218-story.html 

Genomics at the corner of explain evolution of human brain

Scientist at the University of Colorado say that they are inching ever closer to dissecting and explaining the evolutionary genomics of the human brain. By sequencing the DNA of animals related to humans and locating the genes responsible for brain growth and development researchers are moving closer to the cusp of the how the human brain came to be. Aside from lack of anthropological technique, the complete sequence of of a human can't tell us all we need to know about the human brain. In fact, just trying to pinpoint all the genes responsible for the brain itself has proven to be a difficult task. The researchers are using marmoset because they are primates that operate in social groups and are able to be handled with relative ease.

The last few years scientist have been able to identify more sections responsible towards brain development in the marmosets but genes relating directly to social and cognitive portion of the brain are still unknown. According to the research there has been a couple of studies on proteins that play a role in the synapse and altered forms of the gene SRGAP2 are found in humans and Neanderthals and not the marmoset. This suggest the gene plays a new role.

Hopefully this research will continue to flourish and provide us with new information as to how the pivotal standing difference (the brain) of humans and other primate came to be. I would personally like to undergo this specific research itself if possible.

Main article: http://www.sciencedaily.com/releases/2014/07/140709095342.htm

Related article: http://www.kavlifoundation.org/science-spotlights/evolution-what%E2%80%99s-uniquely-human-about-human-brain#.VHE8BvnF83m

Mysteries of the human brain revealed as scientists release detailed 3D image of its genes and pathways

Due to recent research, scientist have now generated the first detailed pictures of the intricate events in the womb that result in the formation of the human brain. this study could be a breakthrough in understanding cognitive disorders developed before birth, such as autism to schizophrenia. This research has been developed by researchers at Allen Institution of Brain Study in Seattle, which was funded by Microsoft billionaire, Paul Allen. These researchers analysed the brains of four human people between 15 and 21 weeks. During these weeks, they build-ed up the first atlas of the developing brain based on the differences in gene activity. Senior scientists believe that these revolutionary new techniques for studying the brain could transform our knowledge of how the brain works, which could lead to radical new forms of prevention or treatment for the many psychological and developmental disorders that have so far defied medicine. This work is part of  a much wider body of research, which aims at a fundamental understanding of the brain. This research is already beginning to show that these  are enriched in the human frontal coretx, which is the part of the brain that is said to be responsible for conscious control over other parts of the brain. with this study/research in continue still, this could lead to unprecedented clues to he molecular underpinnings of what makes the human neocortex. I believe that this research is a great step into understanding where and what causes cognitive disorders developed before birth. Being able to blueprint the brain and generated the first detailed pictures of the intricate events in the womb is a huge step in brain studies. This could a giant step into possibly curing cognitive disorders, with due time. 

Original article: http://www.independent.co.uk/news/science/mysteries-of-the-human-brain-revealed-as-scientists-release-detailed-3d-image-of-its-genes-and-pathways-9233660.html

Secondary article: http://www.livescience.com/23313-human-brain-atlas-disease.html

Critical Role of One Gene to Our Brain Development

Researchers at the University of Adelaide have confirmed that a gene linked to intellectual disability is critical to the earliest stages of the development of human brains. The gene is known as USP9X, has been investigated by Adelaide researchers for decades but only recently have they discovered the importance of the gene. Located on the X-chromosome, USP9X controls both the initial generation of the nerve cells from stem cells, and also their ability to connect with one another and form the proper networks. In a new paper published by the University of Adelaide's Robinson Research Institute in the American Journal of Human Genetics, explains how a mutations in the USP9X gene are associated with mental disabilities and that these mutations can be inherited from one generation to the next. This is the same gene that has also been found to stop the spread of pancreatic cancer just by reactivating it. 

This is a great step toward learning how the brain works. If we can continue to discover how the brain develops and what genes cause certain disorders, we can be able to cure many of these disorders that cause people to suffer everyday. Also, we are now seeing that USP9X is a very important gene for our development so if we continue to research this gene, who knows what else we can discover. 

Brain Development in Infants Linked to Alzheimer's

Researchers from Brown University and Banner Alzheimer’s Institute have found that infants who are carriers of the gene associated with Alzheimer’s also have different brain development than those who do not have the gene. The gene linked to Alzheimer’s is APOE-E4.

After taking images of 162 healthy brains of infants between 2 and 25 months, researchers found that infants happened to have an increased growth in the frontal lobe and decreased growth in the middle and rear areas of the brain. Although these findings do not indicate that these infants will definitely have Alzheimer’s later in life, it shows that there is a difference in development from infants who do not have the gene for the disease.

In discovering this difference in infant brains among those who are genetically set up for Alzheimer’s enables us to better understand the disease and what is happening. If we further our knowledge with studies such as these, we will be able to better detect and possibly find better treatments for Alzheimer’s.

Original Article