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The biology of how the brain forgets

Our brain tends to forget things that we wish we would always remember. And yet, it cannot forget certain things we wish never occurred and existed. How does your brain forget? And, can your brain forget on purpose? By nature, the human brain forgets. Inopportunely, the biological mechanism underlying this brain process is poorly understood. Only few studies shed light on this aspect. In May 2012, scientists attempted to explain the molecular biology of active elimination of memories on their report. In September 2018, another team of researchers identified the parts of the brain associated with forgetting. Based on brain frequencies, they analyzed how the human brain voluntarily forgets.

 

 

 

Molecular biology of forgetting

In 2012, an independent research team from the Scripps Research Department of Neuroscience attempted to understand the molecular biology of active forgetting.1 To do so, they used fruit flies (Drosophila) as key model since this species is often used for studying memory. Accordingly, they found that a small subset of dopamine neurons regulated the acquisition as well as the forgetting of memories. In other words, they saw that the neurons that acquired memory on one hand also eliminated the memory on the other hand. Notably, they identified the two dopamine receptors involved, i.e. dDA1 and DAMB.

 

In this case, dopamine, a neurotransmitter, seemingly performs dual, yet opposing, roles. At first, the dopamine activates the dDA1 receptor of a neuron. In effect, the neuron begins forming memories. However, the same neuron sends out signal via another dopamine receptor, DAMB. As dopamine binds to the DAMB receptor, it activates the receptor. As a result, it triggers events that lead to the forgetting of the recently acquired memory (provided that the memory has not been consolidated yet). A process, called consolidation, protects important memories from being forgotten. In essence, while memory actively forms, a dopamine-based forgetting mechanism works as well. Unless the brain reckoned the memory as important, it erases the forming memory.

 

 

 

Forgetting on purpose

In September 2018, researchers from Ruhr-Universität Bochum and the University Hospital of Gießen and Marburg collaborated with researchers from Bonn, the Netherlands, and the UK.2  In brief, they identified the parts of the brain involved in the process of voluntary forgetting. In particular, these brain areas include the prefrontal cortex and the hippocampus, the brain region associated with memories.

 

In this recent study,  the researchers found that the prefrontal cortex regulates the activity in the hippocampus. One of the leaders of the team, Carina Oehrn, explicated that the prefrontal cortex suppressed hippocampus activity. Further, she noted that the frequency changed. Accordingly, the difference in frequency caused the currently processed information to cease from being encoded. They referred to this frequency as the forgetting frequency.2

 

 

 

Forgetting – crucial to health

biology of forgetting - post-traumatic stress disorder
A Marine attended art therapy to relieve post-traumatic stress disorder painted this mask. Credit: Work by Cpl. Andrew Johnston, and released by the United States Marine Corps.

 

As much as recalling is important, forgetting certain things is pivotal to mental and emotional well being. We inherently forget on purpose. Imagine remembering all – both good and bad. Not only we would have to deal with information overload but we would also be long exposed to feelings associated with those memories.

 

Post-traumatic stress disorder, regarded as a mental disorder, develops when a person has gone through a traumatic event. People with this condition face higher risks of inflicting self-harm, or worse, committing suicide.3 Hyperthymesia, a condition wherein an individual can extraordinarily recall much of one’s life in vivid and perfect detail, can be off-putting and distressing to the affected individual. Based on one such case, the patient recounted how the ability to remember constant, uncontrollable chain of memories could be exhausting and a burden.4

 

 

More research

The metaphorical inability to forget hinders a person to move on and focus on the tasks at hand. Traumatic events seem to be ingrained deeply in mind and soul. For instance, loss of a loved one, warfare, and sexual assaults prove to be difficult to ignore. Thus, we need more insights on the neuro- and molecular biology of forgetting. More studies could help shape up future therapeutic intervention. It may not necessarily lead to the absolute incapacity to recall. But, hopefully, it can help set aside spiteful memories. In that way, affected individuals could be freed from the traps of the past, and help them live life with a sanguine hope for a future.

 

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1 Sauter, E. (2012, May 14). “Team Identifies Neurotransmitters that Lead to Forgetting”. The Scripps Research Institute. Retrieved from https://www.scripps.edu/newsandviews/e_20120514/davis.html
2 Ruhr-University Bochum. (2018, September 7). This is how the brain forgets on purpose: Two brain regions apparently play a pivotal role in forgetting. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2018/09/180907110501.htm
3 Bisson, JI; Cosgrove, S; Lewis, C; Robert, NP (2015, November 26). “Post-traumatic stress disorder”. BMJ (Clinical research ed.). 351: h6161. doi:10.1136/bmj.h6161. PMC 4663500
4 Parker ES, Cahill L, McGaugh JL (2006, February). “A case of unusual autobiographical remembering”. Neurocase. 12 (1): 35–49. doi:10.1080/13554790500473680.

How cell fixes DNA damage

DNA repair strategies – overview

DNA is crucial to life. It carries the fundamental blueprint for the proper functioning of a cell. Thus, a damaged DNA could indicate trouble. A mere structural change could lead to the disruption of the genetic code crucial to the building of proteins. Without an apt and prompt DNA repair, mutation arises. Many of these mutations can lead to genomic instability, and ultimately to metabolic dysfunctions, aging, or diseases, such as cancer. DNA repair strategies are of two major classes: (1) the direct reversal of the chemical process that caused the damage and (2) the replacement of damaged nitrogenous bases.1

 

 

DNA repair by direct reversal

The integrity of DNA structure must be kept up at all times as much as possible. Otherwise, the cell would not be able to function as it normally would. Inopportunely, DNAs are prone to damage when exposed to certain mutagens, such as radiation and chemicals. Exposure to them could lead to the incorporation of an incorrect nucleotide during DNA replication.1 One way to correct this is through a direct reversal DNA repair mechanism. In this DNA repair strategy, a template is not required and the change is superseded as the original nucleotide is restored.

 

 

DNA repair by excision

Damaged DNA may also be repaired by excision. Unlike the first DNA repair mechanism that does not require a template (as described above) DNA repair by excision requires one. DNA is a double helical structure. Because of this, the undamaged DNA strand could be used as a basis when correcting the damaged strand. It is done so by excising and replacing the damaged DNA with new nucleotides. There are three forms of excision repair: (1) base-excision repair (where a single nucleotide change is recognized and subsequently excised by glycosylases), (2) nucleotide excision repair (where multiple base changes are recognized and then cleaved by endonucleases), and (3) mismatch repair (when mismatched bases are later recognized and eventually corrected by excising the error). All these excision repair mechanisms lead to the definitive restoration of the original sequence.1

DNA repair mechanisms

 

 

Recent study on DNA repair

A recent study by a research team from the University of Southern California reported a DNA repair mechanism in fruit fly cells and mouse cells. They likened the mechanism to an emergency responding team. Accordingly, the DNA repair mechanism of the cell includes a team of paramedics (i.e. myosins) that carry damaged DNA to an emergency room (i.e. nuclear pore) located at the periphery of the nucleus. They found that broken DNA strands prompt a series of threads, called nuclear actin filaments, to assemble and form a transient “road” that links to the edge of the nucleus. The myosin (i.e. a protein conveyed to be “walking” because of the presence of “two legs”) treads the road formed by the nuclear actin filaments while it carries the injured DNA strand towards the nuclear pore. The nuclear pore is viewed by the researchers as the emergency room for damaged DNAs since it is where the cell repairs them.2

An illustration depicting myosins that act as paramedics carrying damaged DNA along nuclear actin filaments, which serve as a transient road towards the nuclear pore. (Illustrator: Vix Maria ©Biology-Online.org)

 

 

The cell with its own scheme for DNA repair is indeed remarkable. DNA carries the code that specifies how proteins are made. Without the cell’s innate ability to correct DNA damage, its integrity would be impaired as well. Two major strategies arise: one that rolls the error back to the original and the other that replaces the damage anew based on a template. The recent findings on DNA repair mechanism on fruit flies and mouse cells revealed how remarkable the process already is and how it can pave the way for more highly anticipating research in humans.

— written by Maria Victoria Gonzaga

References:
1 Farrar , S. (2018). Mechanisms of DNA Repair. Retrieved from https://www.news-medical.net/life-sciences/Mechanisms-of-DNA-Repair.aspx
2 University of Southern California. (2018, June 20). The world’s tiniest first responders: ‘Walking molecules’ haul away damaged DNA to the cell’s emergency room. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2018/06/180620170951.htm

Intermittent Fasting – benefits and caution

Intermittent fasting recently gained popularity as an alternative way to keep one’s weight in check. Its basic tenets, though, go against what we had been previously told – to never skip a meal, especially breakfast. We have been accustomed to eating “like a king” as soon as we wake up to prepare the body for the toils and turmoils of the day. Intermittent fasting, though, says that it is alright to put that first meal off until you reach the time window for “feasting”.

 

 

 

Intermittent fasting – overview

Intermittent fasting promises profound health benefits. Accordingly, it can slow down aging, boosts immune defense, and help shed the extra weight.1 All the health benefits are seized if it is done properly. Intermittent fasting is a cycle between a fasting period and a non-fasting period. It may be done in two ways: whole-day fasting and time-restricted eating. Whole-day fasting is the more stringent form. It entails a 24-hour fasting done twice a week (5:2 plan) or every other day (1:1 plan). Time-restricted eating is a daily cyclic period of 16 hours of fasting and 8 hours of non-fasting. The periods are flexible. The pattern can be 12:12 (i.e. equal periods of fasting and non-fasting) or 23:1 (wherein the non-fasting period is set for only one hour). There are no restrictions as to the amount and the kinds of food to eat although consumption of healthy food within the recommended amounts during the non-fasting period is ideal.

 

 

 

Intermittent fasting – recent studies

Kim and others conducted a research on mice and they found that intermittent fasting helped to kick-start the metabolism and to burn fat by generating body heat in mice. Further, they found that during the fasting period there was an increase in the expression of vascular growth factor, a biochemical essential in angiogenesis and in activating the anti-inflammatory macrophages in white adipose tissue.2 Intermittent fasting may also help improve the ability of intestinal stem cells to regenerate as observed in a study in both aged and young mice by MIT biologists. Accordingly, it seems to have induced a metabolic switch in the intestinal stem cells causing the cells to preferably break down fatty acids instead of glucose.3 These are just some of the studies implicating the potential benefits of intermittent fasting, such as body fat reduction, adipose thermogenesis, metabolic homeostasis, and the preferential utilization of fat-derived ketone bodies and free fatty acids as energy sources via ketogenesis.4

 

 

 

Intermittent fasting – is it for all?

Intermittent fasting – a cyclic period of fasting and feasting

 

In spite of the purported health benefits of intermittent fasting, this weight loss modality is not recommended for all. Instead of being beneficial, it may be detrimental to the health of those who are immunocompromised and underweight. 4 Thus, consulting a physician should be the initial step. The extent of the positive effects may also differ from one individual to another. Despite the various studies highlighting the health benefits of intermittent fasting, they were done mostly on rodent models. Therefore, further studies are required to validate such promising results in humans.

 

 

 

Unless substantial studies to corroborate the health benefits of intermittent fasting are presented, a window of doubt remains. If in time intermittent fasting proves to be beneficial it would still lead to further queries, e.g. which fasting cycle is the ideal. Also, the effects may vary between young and older people, or between men and women especially when hormones are taken into account. Thus, similar to other weight loss modalities, it is possible that intermittent fasting may work for some people but not for all.

 

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1Cohut, M. (2018). Intermittent fasting may have ‘profound health benefits’. Retrieved from https://www.medicalnewstoday.com/articles/321690.php
2 Kim, K.H., Kim, Y.H., Son, J.E., Lee, J.H., Kim, S., et al. (2017). Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage. Cell Research, 27: 1309-1326. https://www.nature.com/articles/cr2017126′>10.1038/cr.2017.126
3 Trafton, A. (2018). Fasting boosts stem cells’ regenerative capacity. Retrieved from http://news.mit.edu/2018/fasting-boosts-stem-cells-regenerative-capacity-0503
4 Longo, V. D., & Mattson, M. P. (2014). Fasting: Molecular Mechanisms and Clinical Applications. Cell Metabolism, 19 (2), 181–192. http://doi.org/10.1016/j.cmet.2013.12.008

Can dogs really recognize human emotional expressions?

Have you experience crying and then your pet dog suddenly comes to you try to pacify you with a lick on your face? Many pet dog owners believe that their dogs have the ability to detect certain human emotional expressions, for instance, sadness. (more…)