Wednesday, May 2, 2018

Alzheimer's and Iceland

Alzheimer’s and Iceland

            Just try to picture this: You call up one of your parents to ask them how their day went, just a simple act, but for some reason they have no idea who you are and begin to get agitated. This person who raised you and watched you grow, who knew you better than you knew yourself, suddenly treats you like a distant stranger. Alzheimer’s disease is characterized by an accumulation of insoluble deposits of Amyloid βin the brain. Alzheimer’s is a terrible disease that not only affects the patient, but tremendously impacts their loved ones as well. And we still know very little about this destructive disease.
            Dr. Subhojit Roy from the Wisconsin Alzheimer’s Center at Wisconsin University Madison discussed his research with a unique technique known as the CRISPR/Cas9 method which interferes with the production of beta-amyloids by altering specific proteins involved in the process. His research focuses on limiting the cleavage of amyloid precursor protein which might contribute to a lower risk of Alzheimer’s. In his research article, Dr. Roy mentions the Icelandic population and their inherent genetic advantage to a lower risk of Alzheimer’s.
            A lot of studies have been done concerning Iceland’s genome and all studies return a wide range of information regarding their unique advantage for escaping disease. In one particular study, a small percentage of the population was found to have a mutation with a protective variant against Alzheimer’s. 

To read more about this study click here: 


How Sleep Is Essential to the Brain

Many can relate to how, as a full time college student, it is sometimes difficult to find sleep. There always seems to be an excuse for not sleeping. Whether it be getting home late from work, wanting to stay up and socialize with friends, cramming for a huge exam, or starting a 10 page research paper that’s due the following day there always seems to be a reason for me to neglect my body of sleep. The sad reality is that I’m not the only college student that struggles to find time to sleep. According to “23 Sleep Deprivation Statistics in College Students” only 11% of college students report getting enough sleep. Lucky them. 7 out of 10 college students report getting less than the recommended amount of sleep, 35% stay up past 3am at least once a week, and 20% of students will pull at least 1 all-nighter every month. There is so much happening in college, and so much information for us to absorb. But depriving myself of sleep is certainly not making it any easier for me to remember the steps of glycolysis. Sleep is so important to the formation of memories, and with so much to learn from college classes, sleep becomes all that more important. Your brain needs that time to process the information that it has received throughout the day and organize the important information from irrelevant details. Sleep is essential in the formation of memory, and enhances our brains ability to recall memories and make room for new information.
            The article “Sleep Shrink’s the Brains Synapses to Make Room for New Learning” by Bahar Gholipour presents research showing that sleeping creates more room in our brain to learn new information. This happens through a process called synaptic resetting. During the day, as information is being processed by the brain, everything that we experience is being held by the junctions connecting two brain cells: neuronal synapses. The brain is tremendous in that it can somehow store everything that we perceive, but is it necessary to store all of it? While we sleep, the brain processes the information held in the synapses and determine which synapses store valuable information, such as what you learned earlier that day in Cellular Biology, and which synapses hold irrelevant details, like the hair color of the cashier you saw at target. The synapses with valuable information will be larger as the information is recalled numerous times throughout the day, while the smaller synapses store afterthoughts and very unimportant details that aren’t necessary to recall. During sleep the brain targets these smaller synapses and “resets’ them, shrinking them to make way for new information. Researchers observed the brains of sleeping mice and compared them to their brains during consciousness by using electron microscopy and found that 80% of neurons shrink by about 18%. The 20% that did not shrink were notably the largest synapses that held details that were likely important to the rat. In doing this, the brain creates a place for new information to be stored, while allowing synapses with important information to get stronger and larger. Without sleep, the brain could not undergo synaptic resetting, and the brain will have less space for new information to be held, and less space for important information to be better committed to memory.
            Sleep is used by our brain to strengthen synaptic connections for better memory of important information. Research done by Ken A. Pallar of Northwestern University’s Department of Psychology also suggests that while we are sleeping, we can activate important memories during slow wave sleep (SWS) and promote learning of those memories during wakefulness. This is called Target Memory Activation (TMR). Researchers began with a conscious subject. The subject performs a series of memory tasks, some that have an auditory component to them, and others that do not. The subject then goes to sleep. While the subject sleeps, their brain is observed under EEG for SWS. During SWS the sounds associated with the memory tasks from earlier are quietly played. By playing the sounds associated with the memory tasks, brain networks associated with the sound are activated. After waking up, the subject is once again subjected to the same memory tasks as before sleeping, and the accuracy of the sound-associated memories and the non-sound-associated memories are compared. Memory tasks that were associated to sounds were more accurate than those that were not. This shows how crucial a role sleep plays in memory. Memory tasks are made to have information that is difficult for us to associate to memory. By associating this unimportant information with a sound and playing that sound during SWS, the brain networks for the information are stimulated and thus become stronger and more “important.” The article referenced earlier would suggest that the synapses that held the information that was not associated with a sound were synaptically reset, while the synapses stimulated through TMR were spared from shrinkage and allowed to grow. Important information is memorized through rehearsal and reactivation of brain networks holding that information. TMR reactivates those brain networks in our sleep while the brain is organizing important information, preventing them from being shrunk and allowing better recall in consciousness.
The two articles show the incredible things that our brains can do while we sleep. They reduce the memory of unimportant details while enhancing the memory of things that we feel are important. When we deprive ourselves of sleep, we are robbing our brains of the ability to effectively create memories. Learning requires rehearsal and sleep. Students who deprive themselves of proper rest are hurting themselves academically, because new information we learn from class, or that we try to force into our brains at 4am the night before an exam, has no room to grow in our brain. The human brain can do amazing things, but to get the most out of what we learn and experience, we must give ourselves time to sleep and process.  







Citations:



3.     https://brandongaille.com/21-sleep-deprivation-statistics-in-college-students/


Rushing to the Cure for Alzheimer's: A Discussion of Pharmaceutical Methods vs. Gene Therapy

Rushing to the Cure for Alzheimer's: A Discussion of Pharmaceutical Methods vs. Gene Therapy

Alzheimer’s disease is reported as the 6th leading cause of death in the U.S. with currently 5.7 million of affected Americans. This number is expected to rise to 14 million by the year 2050, according to the Alzheimer's Association. With the numbers quickly increasing, research interest has also increased due to the unmet need for a cure. However, a fundamental question remains. What will be the “best” treatment for the disease?
The article, Despite Setbacks, Drugmakers Have Plans to Fight Alzheimer’s, published in The Wall Street Journal, described the plans of several research groups in the pharmaceutical industry. With growing concern, funding for Alzheimer’s disease has nearly tripled since 2013; however, many scientists do not guarantee any ground-breaking progress in the short term. For several years, the pharmaceutical industry has focused on the aspect of dementia in Alzheimer’s, but reversing brain damage is very difficult.
Many researchers in this field believe that beta-amyloid/amyloid plaque leads to the development of Alzheimer’s disease. The heavy focus on the late effects of Alzheimer’s prompted scientists to target amyloid plaque with drugs (solanezumab) but resulted in nonsignificant effects on cognition. Nevertheless, scientists shifted toward catching the disease at earlier stages. Even then, medications like verubecestat which is a BACE inhibitor that prevents enzyme production of amyloid failed to show any benefits. Other drugs like aducanumab, can clear beta-amyloid plaque, but also produce adverse effects. As more pharmaceutical methods are tested, one central conflict persists. The struggle remains in catching the disease early enough for these drugs to work. How early can patients be diagnosed even before prodromal stages?
Dr. Roy (MD. Ph.D.), a neuropathologist and researcher, plans to defeat Alzheimer’s differently. He argues that it may be a product along the pathway of amyloid plaque formation that leads to the disease, rather than the plaque itself.  By using CRISPR/Cas9 methods with gene-therapy, Dr. Roy explained how the Cas9 nucleus cuts specific DNA strands with the help of gRNA (guiding RNA). Essentially, gRNA is a sequence of RNA that is complementary to another sequence in the DNA strand. gRNA forms a complex with the Cas9 nucleus to perform its function. By combining these two components, researchers can direct the enzyme toward a particular point in the DNA and produce functionality analogous to a highly specific designer restriction enzyme. With this in mind, the CRISPR/Cas9 method can alter proteins produced in the genome and truncate the pathway for amyloid plaque production. Therefore, Alzheimer's disease may be prevented due to the inhibition of amyloid plaque production entirely-- all with one injection.
   Whether researchers focus on gene therapy or pharmaceutical methods to treat Alzheimer’s, both concentrations are dealt similar issues. For one, both designs require subjects at earlier stages of the disease, a complex condition to diagnose. Additionally, researchers need more time to test their hypotheses on animal models before even moving into clinical trials. Scientists are setting long-term projects that may take years to complete. Lastly, the cost of these drugs or injections has not been considered yet. Healthcare in America has been a severe societal issue the past few years. If the rate of Alzheimer’s disease cases continues to escalate as projected, government policies should consider regulating the cost of these future treatments. It may be many years until the “best” cure for Alzheimer’s is conceived; however, higher awareness and support from society may expedite the process.

Works Cited

Hernandez, Daniela, et al. “Despite Setbacks, Drugmakers Have Plans to Fight Alzheimer's.” The Wall Street Journal, Dow Jones & Company, 9 Jan. 2018, www.wsj.com/articles/drug-industry-isnt-giving-up-on-alzheimers-1515457652.
Sun, Jichao, and Subhojit Roy. “The Physical Approximation of APP and BACE-1: A Key Event in Alzheimers Disease Pathogenesis.” Developmental Neurobiology, vol. 78, no. 3, 2017, pp. 340–347., doi:10.1002/dneu.22556.

The advantages of fMRI in understanding child development

Talking with--Not Just to--Kids Powers How They Learn Language

In “Talking With-Not Just to-Kids Powers How They Learn Language”, Claudia Wallis from the Scientific American explores the anatomical mechanisms of language development in children, and how a divide in learning development exists across different socioeconomic strata in our society. Wallis cites a 1995 finding by Betty Hart and Todd Risley to explain that, by age four, children raised in poverty have heard 30 million fewer words than their wealthier peers. This gap in language development has been found to be a predictor for weaker academic performance among children from lower socioeconomic backgrounds. Wallis qualifies this finding with the fact that it is not just the sheer number of words, but also the act of having back-and-forth conversations (often called conversational turns or contingent talk among researchers) with children that improves their language skills.
Wallis cites a paper recently published in Psychological Science, in which researcher John Gabrieli employed fMRI (functional Magnetic Resonance Imaging) to find the anatomical bases of language development in 36 children aged four to six. The study found that parents from higher socioeconomic backgrounds engaged in more verbal exchanges with their children, and this translated to higher verbal ability scores when compared to children from lower-income families. fMRI scans showed that the Broca’s Area (associated with language and speech production) was more active when children with higher verbal ability scores listened to short recordings of stories. Wallis explains that these findings are important because we are living in an era where both children and adults are spending less time using face-to-face communication and more time with their devices. Wallis qualifies this concern by citing a 2017 finding by K. Hirsh-Pasek, in which it is established that when a cell-phone call interrupts a parent-child teaching interaction, the child’s learning is lost.
The studies Wallis cites substantially mirror Elizabeth Wakefield’s lecture on the importance of self-generated actions in novel verb-learning tasks in children. She discusses how fMRI technology has been employed to find that children who are given the opportunity to actively explore objects while learning novel verbs have improved connectivity in their sensorimotor systems, allowing for more concrete learning (James & Swain, 2010). The researchers found that the sensory and motor systems significantly interact during perception, and therefore greater activation of a child’s motor system improves their ability to learn action-verbs. This is due to the fact that the motor system experiences greater BOLD (Blood-oxygenation level-dependent) signaling when a child imagines physically manipulating an object in order to recall the action-verb they previously performed.

As we can see, both researchers employed fMRI technology to find that allowing children to perform self-generated actions improved their neuronal connectivity and learning development. Wakefield explored the importance of the sensorimotor pathway in helping children learn novel action words through active engagement with objects. Similarly, Gabrieli’s study examined the function of the Broca’s Area in children’s language development. It can be seen that encouraging children to physically or verbally engage rather than demonstrating these actions or words improves their overall learning development. The fMRI scans performed for both Wakefield and Gabrieli’s research have demonstrated this finding in separate brain networks. While Wakefield’s research found that the motor system is activated when children imagine previously performing certain actions, Gabrieli found that the Broca’s Area is activated when children imagine verbally responding to the words they are hearing. This shows that active engagement during working memory tasks and long-term memory encoding is important in multiple facets of a child’s cognitive development. These findings can even be translated to the learning process in adults, showing that learning by doing is more effective than learning by listening.


All it takes is 66 Seconds


Every 66 seconds someone across the globe is phased with Alzheimer's. Unfortunately this neurodegenerative disease succeeds in destroying memory and other essential mental components needed for function and everyday processing. With the drastic spread of this worldwide disease in the elderly population (typically ages 65 and older) the race to find the cure continues.

Among the many research studies that have been conducted, Dr. Roberto Fernandez excels in explaining the root of Alzheimer's and its progressive pathology developed within the brain. The brain is a deeply integrated and complex system, and to indulge in such subject, Dr Fernandez  approaches it by studying particular areas of the brain that are more prone to Alzheimer's. Specifically the hippocampus, which is a huge component for memory formation, and tends to be damaged the most. Dr. Fernandez investigates on a more microscopic scale and concludes that there seems to be the presence of abnormal deposits of protein known as Beta Amyloid. Ultimately these proteins tend to malfunction and accumulate in a great degree of plaque formation, which skews brain function. To put this research into context Dr Fernandez experimented with individuals who had Alzheimer's and their response to driving simulations. Three groups with distinct characteristics were formulated, the first group consisted of young normal control subjects (YNC), the second was older normal subjects (ONC) and the last group was individuals with onset of early Alzheimer's (EAD). Various stimulus were introduced, in which event related potentials were used (N200) to measure the change in environmental stimulus. Dr Fernandez discovered that individuals were able to respond significantly well to the variable of increments in motion. However there was a distinct change in acceleration. It was noted that patients with early stages of alzheimer's had a much lower response to acceleration.

Driving simulation is just one of the everyday examples among many that illustrate Alzheimer's disease and its overtaking and limiting control on the human brain. Over the past few years there has been much research on learning how to speak a second language can delay Alzheimer's and further boost brain power. According to Ellen Bialystok, a psychologist at York University in Toronto, “Being bilingual has certain cognitive benefits and boosts the performance of the brain, especially one of the most important areas known as the executive control system.” Although bilingualism may not directly stop Alzheimer's, it can still play a significant impact on counteracting the presence of it. In other words, performance is higher and individuals are able to cope with the disease for a longer period of time. In Bialystok’s recent research she observed 211 people with a possibility of Alzheimer's disease. 102 of whom were bilingual and 109 monolingual, and noted the age at which the patient's' cognitive impairment had started. Her results showed that bilingual patients had been diagnosed 4.3 years later, on average, and had reported onset of symptoms 5.1 years later than monolingual patients. However on the other end of the spectrum there has been much research that disproves the idea of bilingualism being beneficial towards Alzheimer's disease. Rather it seems to be a conflict and can hinder cognitive development.  

Regardless of the new research and techniques that are being tested or administered, it is evident that Alzheimer's disease continues to expand and be a topic of discussion. Tying both of the research from the articles cannot lead to a simple explanation of the “ideal” cure. However it is important to take into account of Dr. Fernandez and Psychologist Ellen Bialystok’s approach on studying specific elements of the human brain and correlating it to the fundamental characters of neurodegenerative diseases such as Alzheimer's.

Article:


The Memory Implant


                 There are many suggestions on how to improve your memory. From exercise to stimulate the brain with caffeine and all sorts of memory tricks and suggestions on how to remember all the organic compounds and important historical dates. Beyond these ‘classic’ methods of improving memory, exciting new research on the benefits of a brain implant could bring about a concrete process for improving memory. There could be a life-saving machine for patients with Alzheimer’s disease, dementia, and other neurodegenerative diseases affecting memory!

Dr. Joel Voss’s research on associative memory and the hippocampus sparked the idea that significant memory improvement was possible through non-invasive magnetic stimulation.  His study focused on the memory hub of the hippocampus and surrounding areas of the brain in older adults. To determine association areas, fMRI scans were used to track which areas had similar activity patterns to the hippocampus over time. The fMRI scans showed that the lateral parietal cortex had functional connectivity to the hippocampus. After transcranial magnetic stimulation (TMS) there was an increase in the correlation between the hippocampus and association areas. The parietal cortex was stimulated, and its connection to the hippocampus determined improvement in memory post-simulation. After repetitive TMS, participants showed an increase in ability to retain and learn new information. Theta frequency-specific stimulation induced memory enhancement and increased associative memory performance. The study found that the amount of effect on the hippocampus predicted the effect and maintenance of the memory long term. There was a strong positive correlation between the intensity of stimulation and effect on memory. Greater intensity caused a larger effect on the hippocampus and on memory. The participants in the study had a 30% increase in memory of the stimuli in the study. However, there is no indication of whether or not this memory improvement would be permanent or if it would improve memory making outside the study condition.

As the amount of scientific research on the brain grows, the process of memory is beginning to be better understood. And this understanding is leading to breakthroughs and the possibility to manipulate and improve memory processing and storage. Scientists at the University of Pennsylvania and Thomas Jefferson University have developed an implant to monitor electrical activity, with electrodes that can supply stimulating pulses to the brain as it works to store information. The implant would fire electrical impulses when the brain is low-functioning but remain dormant when the brain is functioning normally. The device has shown 15% improvements in memory storage and is further being tested for memory retrieval. Once the implant can assist the brain in memory retrieval, a much higher level of improvement could be achieved. Yet, a study at Washington University in St. Louis showed that memory improvements in remembering long lists of words by associating them with familiar places could occur without an implant. No surgery was required, but the memory improvement did not transfer to storing new information normally. Therefore, before this implant can be commercialized, the extent of its effects on memory outside testing conditions and in normal life should be determined. Though it is an invasive process, it has the potential to enhance memory and combat neurodegeneration.

Reference:
Carey, B. (2018, February 12). The First Step Toward a Personal Memory Maker? https://www.nytimes.com/2018/02/12/health/memory-dementia-brain-implants.html

Looks like Seasonal Affective Disorder has a whole new meaning



         Seasonal Affective Disorder is characterized as short term depression during the months of winter where the nights are long and days are short. Circadian Rhythms are the body's inner biological clock that helps indicate when to sleep, eat, and wake, essentially helping us keep track of time. With certain environmental cues, our bodies work accordingly. For instance, melatonin, a sleep inducing hormone in our body, is released when the our retina receives feedback that it is nighttime. During the long-enduring months of winter, many people fall ill of depression since the body undergoes a state of hibernation and chronic fatigue. Typically one cure for S.A.D. requires light therapy which entails the victim to expose oneself to safe measure of UV rays with artificial lighting. 
There are a myriad of other ways that can affect our circadian rhythm's sleep cycle such as eating too late in the night (and other irregular feeding behaviors), sleeping under too cold or too hot conditions, as well as being genetically predispositioned to an irregular biological clock that fails to code for downstream regulations. Irregular circadian rhythms have a high correlation with many human diseases such as heart disease, diabetes, and cancer.  
However, recent news, has added another factor into our list: road salt. High salinity is affecting microorganisms called Daphnia which are important for algae consumption and are also a huge source of nutrition for fish. Such as how light intensity drives our clock, the mechanics of "dial vertigo migration" works the same for this species and is disrupted by road salt pollution. This term refers to the daily biomass movement in lakes (e.g. tides). By polluting this habit, the ecosystem leading up to our feeding grounds are disrupted as well. Future studies are now looking at other environmental pollutants that may be endangering species such as our own. A midst all this calamity, one can truly imagine how fragile life's balance can be and above all, the importance of diet and sleep.



References:

Hurley, J. M. (2018, January 04). Can Road Salt and Other Pollutants Disrupt Our Circadian 
        Rhythms? Retrieved from https://www.scientificamerican.com/article/can-road-salt-and-other-   
       pollutants-disrupt-our-circadian-rhythms/

King, A. N., Barber, A. F., Smith, A. E., Dreyer, A. P., Sitaraman, D., Nitabach, M. N., . . . Sehgal, A. 
        (2017). A Peptidergic Circuit Links the Circadian Clock to Locomotor Activity. Current     
        Biology,27(13). doi:10.1016/j.cub.2017.05.089