Preventing Cognitive Decline through implementation of Hippocampal-derived Leptin paired with Exercise and Antioxidant Rich Diet

As neuroscience students, we always learn of how terrible and debilitating Alzheimers disease can be. In fact, there have been about 23,000 research papers published concerning this disease over the past two decades with little progress in treating or fully understanding it (Greger 2018).We are certain to learn the biology of this disease such as beta-amyloid plaques, neurofibrillary tangles, and the gene ApoE4 that increases your chances of getting the disease. However, how often are we told and/or taught about Alzheimer's nutritional etiology...never? According to studies 1, 2, and 3, several autopsies of Alzheimer's patients revealed significantly more atherosclerotic plaque and narrowing of cerebral arteries. This consequence is due to the unusually high consumption of processed foods, dairy, and meat products in the United States. A Harvard Women's study revealed that consumption of higher saturated fat from these foods led to overall decline in cognition and memory, which are the key pathologies of Alzheimer's disease (4). Given that our brain uses almost 50% of the oxygen we breathe, it only makes sense to presume that our brain is a prime target for damage from free-radicals and reactive oxygen species(ROS). These ROS's and free radicals can lead to cellular damage, aging, and death. The reasonable solution would be to recommend consuming large sums of antioxidants found in berries, leafy greens, and other whole foods. To much success, this recommendation is a large contributor in reducing Alzheimer's disease, cancer and heart disease. Polyphenol, one of many antioxidants found in berries, "has been shown to protect nerve cells in vitro by inhibiting the formation of plaques and tangles that characterize Alzheimer's,"(Greger 2018). While this information is great, the question still remains, are there any internal mechanisms that are able to slow the spread of such diseases? Dr. Hideaki Soya's 2019 paper "Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory," would say yes. 

One of the key unknown ideas discussed in Dr. Beshel's 2017 paper was the unknown physiological role that brain-derived leptin plays in the body. While Leptin derived from adipose tissue plays a role in satiety signaling, hippocampal-derived Leptin has been shown to "enhance adult hippocampal neurogenesis and synaptic function, which facilitates spatial learning and memory function, suggesting a neurotrophic role of Leptin within the hippocampus, "(Soya et al. 2019). With the positive effects of antioxidants and exercise seen in rodent cognition and memory, Soya et al., decided to test these metrics in relation to hippocampal-derived Letpin. More specifically, they discovered that hippocampal Leptin mediates the beneficial effects of antioxidants and exercise on hippocampal neurogenesis and memory. The three seem to exhibit a synergistic relationship all resulting in up-regulation of brain-derived Leptin genes. Furthermore, Soya et al. measured the effect of infusing Leptin on obese mice lacking hippocampal Leptin. To test this, they used the Morris Water Maze (MWM) assay where the mice were timed of how long they remained in a desired region called the Platform zone. The mice's paths taken to reach this zone were also tested to determine where the mice spent the majority of their time in the maze. 

Figure 5. Central LEP involved in ME +AX-induced enhancement of spatial memory in LEP-deficient mice.

In Figure 5G, you can see that injection of LEP while the mice were given AX and ME resulted in increased time on the platform, which is an indication of the mice learning to navigate the maze. In addition, in 5F, you can see that LEP injected mice had a much more contained path as they were able to better learn their spatial environment. So, what does this mean practically? These data show that a lifestyle stressing the importance of antioxidant-rich diet and moderate exercise is a means to increase cognition and slow cognitive decline. It also offers a potential avenue in slowing and/or preventing neurological diseases such as Alzheimer's. If this lifestyle is able to offer a few more years of cognitive abilities to the aging population, then it is something that should be emphasized in all stages of life.

References:

Beshel, Jennifer, et al. “A Leptin Analog Locally Produced in the Brain Acts via a 

Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in 

Drosophila.” Cell Metabolism, vol. 25, no. 1, 10 Jan. 2017, pp. 208–

217., doi:10.1016/j.cmet.2016.12.013.

Yook, J., Rakwal, R., Shibato, J., Takahashi, K., Koizumi, H., Shima, T., . . . Soya, H. (2019, May 28). Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory. Retrieved October 16, 2020, from https://www.pnas.org/content/116/22/10988

“How Not to Die from Brain Diseases.” How Not to Die: Discover the Foods Scientifically Proven to Prevent and Reverse Disease, by Michael Greger and Gene Stone, Pan Books, 2018, pp. 51–57.

1. Roher AE, Tyas SL, Maarouf CL, et al. Intracranial atherosclerosis as a contributing factor to

    Alzheimer's disease dementia.  Alzheimers Dement. 2011;7(4):436-44

2. Yarchoan M, Xie SX, Kling MA, et al. Cerebrovascular atherosclerosis correlates with 

    Alzheimer pathology in neurodegenerative dementias. Brain. 2012;135(pt.12):3749-56.

3. Honig LS, Kukull W, Mayeux R. Athersclerosis and AD: analysis of data from the US National 

    Alzheimer's Coordinating Center. Neurology. 2005;64(3):494-500. 

4. Okereke OI, Rosner BA, Kim DH, et al. Dietary fat types and 4-year cognitive change in community-dwelling older women. Ann Neural. 2012;72(1):124-34. 

The Science Behind Perception of Beauty

The science community is constantly looking for explanations and processes to everything around and inside us. One big question that has been around for a while is, how does the brain define beauty and how is it processed? Ancient philosopher believed that beauty was a objective matter, meaning that it came from the object itself. As time progressed scientist began to switch over to beauty being subjective. Meaning that an object’s beauty was determined from the brain. This subjective in recent years has come to be known as Neuroaesthetics. Neuroaesthetics is the study of aesthetic perceptions of art, music and any object that arises aesthetic judgment.

In an article titles "Neuroaesthetics: Understanding Our Perception of Beauty" a study conducted by Ishizy and Zeki called  “A Brain Based Theory of Beauty” was analyzed. The researchers used 21 participants and showed them art paintings and music excerpts. These participants were then asked to rate these art pieces from 1-9. One being the least beautiful and nine being the most. During this process they would have their brain activity recorded using fMRI. The fMRI would be used to keep track of the active areas during the process. The results showed that several areas of the brain were active during the presentation of each type of stimulus. However the only part of the reward and pleasure center that was present regardless of the stimulus is the medial orbito-frontal cortex. Another interesting finding is that rating correlated to activation of the mOFC. Meaning the higher the stimulus was rated, the more blood flow was detected to that area. In the same article the author criticized  the field of neuroaesthetics as potentially damaging and something that would turn art into a “right or wrong criteria”. In 1993 Komar and Melamid conducted a study were they asked 1,001 American about their art preferences to determine the USA’s most wanted painting. The final results were nothing out of the ordinary and to most people not typically considered beautiful. 

Dr. Grzywacz and his colleagues on the other hand published a paper called “Is Beauty in the eye of the beholder or an objective truth? A neuroscientific answer”.  This paper aims to come up with a theory that proves that aesthetic response (such as finding something to be beauty) is a very individual and changing. Their goal is not to find a set definition on what constitutes beauty and what doesn’t, but aims to explain why we all have different standards of beauty.  In the first part of their study Dr. Grzywacz analyzed the fluency theory, which states the more fluently perceivers can process an object the more positive their aesthetic response is.  The theory behind the brain preferring fluency is that it is able to process the stimuli better and avoid danger. The brain is trained to process 3 main components of fluency ( aesthetic variables )really well. Those include balance, symmetry and complexity. To analyze the truth behind this theory, they analyzed too major questions “ Do artists have biases for properties like these? and is so are they optimized?. The way these questions were answer is by digitized images are stored as arrays of intensity values, often from 0 to 255 or 0 to 1. Balance was demonstrated with similarities in number found in the right and left side. Complexity was analyzed by trying to predict points in the image. Three groups of images were analyzed renaissance paintings, spontaneous pictures, and carefully posed portraits. In the end each painter had a high degree of individuality on how they paint. Meaning their ideas on what makes a painting beautiful was very different and intentional. The main theory this research article came up with is “The theory on how the brain learns aesthetics”. The overall summary is a Person is looking at object. The person needs to make a prediction on the object. The predictions will be made based on the color, shape, size etc. The person will determine whether the object is good or not. If they decide it is, the person takes the action on the object. The decision can either be good or bad. If it is good the object gives pleasure. If the object is not good to, there is a mistake in the prediction. The person then changes the prediction model to make better predictions in the future. No change is made for the positive aesthetic response. A person’s aesthetic response can be influenced by motivation and culture during the learning phase, which can lead to aesthetic individuality. This was shown through a study that determined that risk takers appeared to like higher levels of complexity in their paints versus risk avoiders which preferred balance. The second major conclusions in this paper is that people can learn aesthetic values. This was tested by having participants play a game where they learned to predict reward based on the images they got, participants did not know which had the highest reward. Initially the participants were favoring the images with the highest number of dots were associated with the bigger reward. However, over time they noticed a specific image with a specific number of dots was tied to the highest reward. This made them change their previous favored images. Lastly their final study concluded that aesthetic values can change over time. This was shown by asking participants which was their favorite shirt, and then asking three days later. Most people changed their answer.

Overall it seems that every person may have the same areas of the brain that activate when they see something they consider beautiful such as the anterior insula and the orbitalfrontal cortex but everyone has different criteria that define beauty. It appears that the perception of beauty is both subject and objective, since it is influenced by culture but also triggered by aesthetic values. Neuroaesthetics is not a limiting field and is constantly evolving, discovering and understanding a human's complex mind. 

Citations: 

·      Aleem, H., Pombo, M., Correa-Herran, I., & Grzywacz, N. M. (2019). Is Beauty in the Eye of the Beholder or an Objective Truth? A Neuroscientific Answer. Springer Series on Bio- and Neurosystems Mobile Brain-Body Imaging and the Neuroscience of Art, Innovation and Creativity, 101-110. doi:10.1007/978-3-030-24326-5_11

·      Masri, Y. (2019, June 06). Neuroaesthetics: Understanding Our Perception of Beauty. Retrieved October 16, 2020, from https://medium.com/swlh/neuroaesthetics-understanding-our-perception-of-beauty-eabf06fc65a3

The Obesity Crisis

    Obesity involves excessive body fat which increases the risk of many other diseases. This can cause a variety of complications in an individual’s life regardless of age. It is a very common disorder that affects many individuals throughout the world. In the United States, there are more than 3 million cases per year (“Obesity”).As Dr. Beschel mentioned in her presentation, the obesity crisis has twice as many projected deaths than Covid-19. She also mentioned that zero countries have succeeded in decreasing obesity in the past 33 years. These increasing numbers inspire many researchers to look into the environmental and genetic factors that contribute to obesity. 

    Dr. Jennifer Beschel spoke about how obesity can be caused by both environmental and genetic factors. In the article, “A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila”, the researchers studied weight gain in common fruit flies. They looked at the upd1 gene which has a similar function to leptin. First, they addressed if modifications in the brain differed in weight gain from the flies that were not modified. They found that the flies with modifications had more weight gain which demonstrates that obesity can be caused by genetic factors. Next, they experimented with the environments that the flies were placed into. The knockout flies had high sugar and high-fat diets in the obesogenic environment. The flies with the normal environment did not show as much weight gain as the flies in the obesogenic environment which showed a drastic increase in weight. This relates to the human population because individuals that have a healthy diet are less likely to be obese than individuals with high-sugar and high-fat diets. 

    In the research article, “Family food environment factors associated with obesity outcomes in early childhood”, the researchers studied the environmental factor of family food by looking at the eating behaviors of Australian children. Behaviors such as enjoyment of food and approaching food are positively linked to obesity and the opposite behaviors such as avoiding food and eating slowly are negatively linked to obesity. They found that children with non-responsive feeding practices had a strong relationship to childhood obesity. The article does consider that there may be other reasons such as family climate which can contribute to non-responsive behavior. However, they were able to conclude that the family food environment influences the risk of obesity and obesogenic behaviors. This article correlates to Dr. Beschel’s research because they both present how unhealthy foods influence obesity risk. 

    Although both Dr. Beschel and the other article acknowledged that there are many factors related to obesity, they both presented compelling data about unhealthy foods and how they are positively associated with obesity. The flies gained weight when they were put into the obesogenic environment with high fat and high sugar diets. Similarly, the children showed responsive behavior for unhealthy foods. Both of these lead to an increased chance of developing obesity. Thus, research needs to be conducted on obesity and individuals need to be informed of the results. This allows them to learn about the dangers of obesity so they can control their diets accordingly. 

                                                                

                                                                 Works Cited 

Beshel, Jennifer, et al. “A Leptin Analog Locally Produced in the Brain Acts via a 

Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in 

Drosophila.” Cell Metabolism, vol. 25, no. 1, 10 Jan. 2017, pp. 208–

217., doi:10.1016/j.cmet.2016.12.013.

Boswell, N., Byrne, R. & Davies, P.S.W. Family food environment factors associated with 

            obesity outcomes in early childhood. BMC Obes 6, 17 (2019). 

“Obesity.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 

            15 Feb. 2020, 

            www.mayoclinic.org/diseases-conditions/obesity/symptoms-causes/syc-20375742. 

The Modern Conception of Beauty

     Beauty is something people come across every day. People find beauty in different colors, shapes, objects, sounds and so much more. Many artists over time have tried to construe their perception of beauty through different forms of the arts (painting, music, etc). The interesting fact is that not everyone perceives beauty in the same way and that could be a construct that is molded over time. Being able to observe beauty in different perspectives and forms allows a person to dive deeper into that particular section.
    In the article, "The Brain and the Experience of Beauty"  (2019) by Dr. Noberto Grzywacz and colleagues find ways to understand the beauty of something and how people perceive the aspects of beauty. They found that over time, much art has shown that there is no major symmetry in certain portraits, sculptures and more. Dr. Gryzwacz and team worked with the ideas of a objectivist view and a subjectivist view to understand if the beauty lies in the object itself or if the person themselves comes up with the quality of that object. There was much research to combat both sides of the story and it only makes a person wonder about it more. How does a person know what beauty is? Does it come from the quality of the object? Or does it come from some subconscious that we develop over time? Understanding beauty is not something one person can look at and say "that is beauty" because another could come and disagree. Then how does the world know who is right?
    Another article, "Cognitive-Developmental Education Based on Stages of Understanding Experiences of Beauty" (Rhett Diessner et al, 2016) studied the notion of beauty and how cognitive development changes with experiences related to beauty. Diessner et al. (2016), also discuss how other researchers have drawn up stages of cognitive development and how beauty is intertwined with or influential to people. This is an important study because at some point, everyone may experience beauty but depending on age and development that observation may be seen differently between two or more people. 
    Bringing in the two articles in important for not only distinguishing what beauty may be and how the brain experiences it, but also for understanding how the perception of beauty evolves with age. Perception of beauty can be observed and conceptualized but this is something that occurs without a person being truly aware of the cognitive changes occurring. Beauty from the Renaissance can be argued to be very different to beauty today. That make come from differences in the times, but also come from the constant development of minds in new ages and how things are never staying the same. 

References:
Aleem H., Pombo M., Correa-Herran I., Grzywacz N.M. (2019) Is Beauty in the Eye of the Beholder or an Objective Truth? A Neuroscientific Answer. In: Contreras-Vidal J., Robleto D., Cruz-Garza J., Azorín J., Nam C. (eds) Mobile Brain-Body Imaging and the Neuroscience of Art, Innovation and Creativity. Springer Series on Bio- and Neurosystems, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-030-24326-5_11

Rhett Diessner, Lana Schuerman, Amy Smith, Kelsey Marker, Alex Wilson, & Katherine Wilson. (2016). Cognitive-Developmental Education Based on Stages of Understanding Experiences of Beauty. The Journal of Aesthetic Education, 50(3), 27-52. doi:10.5406/jaesteduc.50.3.0027