What is clear from this recent paper (Neal et.al. Patterns and rates of exonic de novo mutations in autism spectrum disorders, Nature, advance online publication, http://dx.doi.org/10.1038/nature11011) is that ASD is highly polygenic in origin, i.e. hundreds of genes influence autism risk. Getting to this answer, including two genes in particular that were determined to be very strongly linked with autism (CHD8 and KATNAL2), was a real technical achievement in that in involved analyzing the genomes of 175 trios (mother, father, autistic child). Sequencing 525 human genomes is something that would have been unimaginable just a few years ago. While it is clear that we still have much to understand about this complicated disease, the technological limitations that previously limited progress are beginning to fall away. Hopefully many more important clues are just around the corner.

In memory, we understand the process of encoding memory involves a process called long term potentiation (LTP). A neuron signals another connected neuron through the release of neurotransmitters (chemical messengers) that span the gap between neurons called the synapse. As neurons become linked through LTP, one of the ways the receiving neuron can strengthen this connection is by having more receptors sensitive to incoming neurotransmitter messages. One of the problems for translating this LTP mechanism into a model for memory is that these cellular receptors (and just about all of the cellular machinery involved in LTP) are transient. So how can molecular receptors that come and go be used to store memories that last a lifetime?

Work published here by Craddock et.al in the March PLoS Computational Biology provides an intriguing hypothesis that may help to explain how the brain stores persistent, long-term memories. According to this group’s hypothesis microtubules might be the storage medium behind the brain’s capacious memory storage. Microtubules are ubiquitous proteins (assembled from tubulin) into tube shaped networks that makeup the cell’s cytoskeleton. In the PLoS paper, they propose a schemata whereby phosphorylation of microtubules by CaMKII could serve to create storage and logic gates that would enable the brain to store information.

While there are several unknowns presented in the paper, and I at least am cautious to accept taking metaphors too literally, further experimental evidence could bear out that the brain functions very much like a Turing machine.

More importantly, Bexarotene is already in use in human patients, making it easier to determine if the drug will have similar benefits for Alzheimer’s patients.

According to Alzheimer’s Foundation statistics, 5.4 million Americans suffer from this debilitating disease. Alzheimer’s devastates patient’s cognitive abilities, with the most notable symptom being profound and worsening memory loss. While some amount of memory loss is to be expected with old age, Alzheimer’s patients lose the ability to recognize family members, their surroundings, and ultimately require 24-hour care and hospitalization.

Alzheimer’s is thought to be the result of the building up of beta-amyloid proteins, which coalesce into plaques within the brain. In addition to effects on the mouse immune system which could help clear plaques, treatment with Bexarotene seems to modulate the production of ApoE (Apolipoprotein E), an important cholesterol transporter that can interact with and clear these beta-amyloid proteins.

If this treatment works as well in humans as in mice (where effects were noted within hours of treatment) we should know soon if there is a new hope for those affected by this devastating ailment.

Unfortunately very little is known about how this disease develops, so a new breakthrough published in Neuron (and by a second group also in Neuron) is reason for hope. Work by two independent groups uncovered a locus on chromosome 9 (actually an expansion of repetitive DNA in a non-coding region called C9ORF72) is implicated in at least a third of ALS cases. This sequence variation seems to affect the cells ability to recycle and cope with damaged proteins; when these proteins fail to be properly processed, the cell is damaged an ALS is the result. While this research may not explain all the causes of ALS, it is an important landmark in the battle against this illness, and provides a target for future research and therapeutic intervention.

Of course, we also know that environment can play a strong role in determining a disease outcome. For identical twins in their first environment,  the womb, each individual had slight environmental differences the moment the zygote split into two.  As identical twins develop, there will always be some environmental differences, many of which are still not fully understood. Before we explain this mystery of differences between identical (or more accurately “semi-identical”) twins as a matter of nature vs. nurture, there is another component that requires consideration.

There are other ways that DNA can be modified which don’t involve changes in DNA sequence (the order of the DNA’s A, C, T, G chemical “spelling”). These modifications often involve enzymes that can, for example, alter how, or if DNA is transcribed into mRNA. One type these DNA modifying enzymes is methyltransferase, which can add methyl modifications to cytosine (C), often resulting in the suppression of a gene. These types of non-sequence based changes are referred to as epigenetic modifications. Taking the sum of all of the epigenetic modifications gives us the term epigenome, the additional heritable information content of the DNA genome.

In a recent study published in the journal Human Molecular Genetics a paper by E.L. Dempster et.al at the Institute of Psychiatry Kings College in London showed that epigenetic DNA modifications between sets of identical twins can vary by as much as 20%. This study is highly significant in its demonstrating why researches will have to go beyond sequencing the DNA genome of patients and start paying more attention to the epigenome. The Kings College study is the first wide-scale study that brings recent technological advances in epigenetic investigation to understanding psychiatric disorder. The study found epigenetic modifications not only in gene regions already known to be involved in disorders like schizophrenia and bipolar disorder, but has revealed new genes that could be potential targets for drugs. Because epigenetic modification involves chemical modification of DNA, aberrant epigenetic modifications can often be targeted by drugs.  Hopefully further exploration of the epigenome will  yield more clues about these often devastating conditions.

Different cell type (skin cells, neurons, osteoblasts, etc.) start out from less specialized cells, called stem cells. What a cell will become (its characteristics and functions) is also known as the cell’s “fate.” It may seem odd that seemingly simple skin cells can be transformed into cells that make up the thinking brain. However, all cells have a common set of DNA instructions, and it is the collection of instructions that are being actively “read” that determine what fate a cell well adopt.

In this study, two microRNAs (miR-9/9* and miR-124) were introduced into the fibroblasts. These micro RNAs then go on to alter the expression of their target genes. While RNAi can have very specific effects when there is only one target gene, in this case the micro RNAs targeted a set of genes that had global effects on which set of DNA instructions were being carried out by the cell through a process called chromatin remodeling.

Chromatin (the proteins involved in packaging DNA) determines which genes can be read by the cell, and which genes are hidden (unreadable) by the cells. Since microRNAs miR-9/9* and miR-124 act on a system of proteins (the SWI/SNF-like BAF chromatin remodeling complex) these 2 microRNAs have a greatly amplified effect on many sets of genes that are neuron specific.

Unlike other cell types which are easily collected, neuronal cells (especially in specific clinically relevant contexts) are hard to come by. Being able to create neuronal cells in a “one step” process (vs. previous research methods which could transform skin cells to neuronal cells via an intermediate stem cell step) is an advance that has great potential to speed up neuroscience research.

In a study published in Attention, Perception, & Psychophysics, a group of researchers have been examining a condition called “Inattentional deafness.” The group from University College London examined study participants’ ability to detect a sound while focusing intently on a task.

When subjects did a simple version of the computer based task, most recalled hearing a soft tone (that they were not expecting) in their headphones. A very difficult task caused most participants to become totally unaware of that same stimulus.

Although the study may fuel excuses the next time you are accused of not listening, it has more serious implications as well. While a frenetic pace of life puts a premium on people who can “multitask,” this study emphasizes that multitasking is not something the brain has limitless capacity for. Texting, having conversations, or just daydreaming while we are driving, are all instances of things that rob us of our ability to focus. Having any kind of inattentional deafness or blindness may does not necessarily have to cause the level of impairment that alcohol may bring, but may still cost precious seconds of reaction time that could mean the difference between avoiding an accident, or causing one.

Recently, a group from Naples reports that D-Aspartic acid functions as a neurotransmitter in both a mammal the rats (Rattus norvegicus), and a mollusk (Loligo vulgaris). D-Aspartic acid (D-Asp) has been known to scientists for well over a century. However, its role as a neurotransmitter was only now confirmed by the work presented by D’Aniello et.al.

The brain is usually thought of in its own category when considering our organs; deservedly so, since it seems to be the seat of our personal identity, our selves.  Still, the molecules we think of as neurotransmitters (GABA, glutamate, serotonin, etc.) we most often isolated from other parts of the body, and have roles in biology unconnected with neurotransmission.

Presence in the brain is of course not the qualifying factor for describing any particular molecule as a neurotransmitter. The D’Abuello et.al demonstrate not only the presence of D-Asp acid in high concentrations in synaptic vesicles, but also show that there are specific post-synaptic receptors for D-Asp which trigger signal-transduction of cAMP upon binding of the D-Asp ligand.

The response I got was less than enthusiastic. ‘But what’s the point of studying butterflies? Who would fund that?’ These questions are in reasonable complaints on the mind of many, non-scientists and scientists alike. A recent interview with the astronomer Neil deGrasse Tyson touches on the question of whether the exclusive purpose of science is some grand goal of bettering humanity. Certainly, a good deal of progress comes from funding smart people to do new and exceptional science with the hope that interesting findings produced will satisfy immediate objectives as well as serendipitous future outcomes.

I was happy to see the next day this article published in Nature nanotechnology, where silk moth antennae inspired technology that can improve diagnostics for critical diseases such as Alzheimer’s. Often, diagnostics that work on the molecular level work by being able to detect and/or distinguish the presence of certain molecules. For instance, an Alzheimer’s test might work by detecting the beta-amyloid plaques that are thought to be involved in the disease.

When nanopores are used, detection typically involves monitoring some change in the nanopore as a molecule passes through; there may be a change in voltage at the nanopore, or perhaps there is simply size exclusion (e.g.  molecule A can pass through the nanopore, but molecule B cannot). The design of the moth nanopores makes them resistant to clogging, a problem which has hampered previous artificial nanopore designs. The article’s authors speculate that their finding could in fact be used to develop a new Alzheimer’s diagnostic.

Perhaps a day spent observing butterflies is time well spent, rather than idle daydreaming.

As stated on the G2C website, the amygdala is involved in processing emotions, and fear–learning. Concerning the amygdala and fear, the flight-or-flight response is one of the most well known examples. So do people with more “frenemies” have larger amygdalae to help them survive inevitable back stabbing?

According to this paper, while there was a correlation between large and complex social networks and amygdala size, they did not find that the quality of social interaction was behind that correlation. In other words, we don’t know if your brain struggles more to process your relationships with your nemesis, or if works harder to maintain a good relationship with your friends.

Of course, we need to be careful about drawing conclusions about what causes what. Although the size of brain regions tends to indicate their processing capacity, more research is needed to show if a person with a larger amygdala has a better chance at developing a large number of friends or if your amygdala changes with your facebook status.

The article can be found at nature.com/neuro

doi:10.1038/nn.272