The Importance of ADHD Research for Adults and Children

 

The article “The Marketing of Stimulants for Children With A.D.H.D.” in the New York Times, by Perri Klass, M.D., discusses the ins and outs of diagnosing and treating ADHD along with the implications of this journey on children, their parents, doctors and society at large. The article highlights the growing number of those being diagnosed and the significance of what age patients are being diagnosed. One major treatment for ADHD includes the prescription of a stimulant. Klass writes “Although medication should be neither the first nor the only treatment used, some children find that the stimulants significantly change their educational experiences, and their lives, for the better”. There is a large debate on whether ADHD medication should be prescribed to children or not, one of the reasons for the ladder includes possible addiction to a substance later in life, which researchers have seen a rise of Adderall misuse/abuse. Klass’ article also encourages one to factor in how the pharmaceutical companies push medications through doctors and the difficulty for parents to know if their child is being prescribed medication for the right reasons. For both children and adult patients getting this diagnosis and knowing what the best treatment can be difficult.

 Continuation of research on ADHD is important because it will be able to give insight on understanding how one is affected by it and the best ways to treat it. In the study “Top-down attention modulates auditory-evoked neural responses in neurotypical, but not ADHD, young adults” Kwasa et al investigates the deficits held by people with ADHD in comparison to those without it. The study focused on 55 young adults, 20 being neurotypical and 25 with ADHD. Kwasa et al assessed the ability of subjects to maintain attentional focus using a sound test, the researchers used an EEG to measure event related potentials (ERPS) specifically looking at N1 and P3 responses. The results of this test showed “attentional modulation was weaker in ADHD listeners, even though their behavioral performance was no lower” (Kwasa et al). The results of the neural responses recorded show that it is more difficult for those with ADHD to keep their attention on a single subject. This applies to and gives evidence for the daily struggle that many people go through having ADHD, for many staying focused at school or work is much more difficult for someone without ADHD.

 For many adults and children their success at school/work is highly affected by their ADHD and therefore they seek treatment. For many this treatment will be the prescription of a stimulant. As mentioned before there is the potential for abuse of such stimulants and that is one reason, I think Kwasa’s study is important. With the found information doctors can have a better sense of how to diagnose future patients and make sure they are prescribing a drug safely. Kwasa et al write, “our results support the idea that behavioral assessments are less sensitive than neural measures of ADHD”. This shows that maybe there needs to be a change in how doctors diagnose. Continuing research similar to this study will improve the treatment for those with ADHD as well as potentially reduce the amount of people that get addicted to the stimulants by wrongly being prescribed. New research based evidence would hopefully also aid in stopping the pharmaceutical companies pushing their prescriptions for wrongful reasons, which increases patient safety and lowering patient’s cost for treatment.

Resources

Klass, Perri, MD. “The Marketing of Stimulants for Children With A.D.H.D.” The New York Times, 10 Feb. 2020, www.nytimes.com/2020/02/10/well/family/the-marketing-of-stimulants-for-children-with-adhd.html?searchResultPosition=1.

Kwasa, Jasmine, et al. “Top-down Attention Modulates Neural Responses in Neurotypical, but Not ADHD, Young Adults.” The Journal of the Acoustical Society of America, vol. 150, no. 4, 2021, p. A64. Crossref, https://doi.org/10.1121/10.0007633.

 

Multiple sclerosis information

 Dr Chen, discussed the neurobiology of M.s and its mechanics. She discussed that MS is the auto immune inflammatory response to the myelin antigens. And that MS, represents activity in the central nervous system (CNS) . And she also talked a little bit about how MS affects the patient, not only physically but biologically as well. As we know many MS patients it isn't something that constantly affects the patient, but similar to many autoimmune diseases there are phases of remission, and disease known as flare ups. When MS flares up the central nervous system is directly affected, the patient experiences increased fatigue of the arms and legs in some severe cases manifestations can include optic neuritis. And other manifestations can include inflammation in the colon IBD. And lupus. Unlike these other autoimmune diseases, MS causes demyelination and loss of oligodendrocytes as discussed by Dr Chen in her talk.

Relapses are fundamentally a manifestation of an inflammatory response occurring mostly in the white matter of the nervous system but also within myelin tracts in the gray matter. This results in focal demyelination with relative axonal sparing. This would account for the development of optic neuritis. Which affects the sight, this explains blurred vision and loss of vision for the patient. The best evidence for inflammation-induced relapses is confirmed through diagnostic imaging; the most reliable diagnostic we can use when dealing with MS would be MRI. which demonstrates the association of relapses with gadolinium enhancement, so a dye is injected intravenously which is disruption of the blood brain barrier. The main pathologic hallmark of MS is the demyelinated plaque, which has specific histological and immunohistological characteristics depending on the activity of the disease. This is the main indicator to diagnose MS. There have been cases of MS and inflammation causing lesions which are benign. This is most common, in the early phases of the diesease. To diagnose MS, the other diagnostic test used aside from imaging would be simple blood work. The stress induced blood marker that helps indicate MS induced stress kinases is elf2a. This is produced through a simple lab

Multiple sclerosis

 Dr Chen, discussed the neurobiology of M.s and its mechanics. She discussed that MS is the auto immune inflammatory response to the myelin antigens. And that MS, represents activity in the central nervous system (CNS) . And she also talked a little bit about how MS affects the patient, not only physically but biologically as well. As we know many MS patients it isn't something that constantly affects the patient, but similar to many autoimmune diseases there are phases of remission, and disease known as flare ups. When MS flares up the central nervous system is directly affected,  the patient experiences increased fatigue of the arms and legs in some severe cases manifestations can include optic neuritis. And other manifestations can include inflammation in the colon IBD. And lupus. Unlike these other autoimmune diseases, MS causes demyelination and loss of oligodendrocytes as discussed by Dr Chen in her talk.  Relapses are fundamentally a manifestation of an inflammatory response occurring mostly in the white matter of the nervous system but also within myelin tracts in the gray matter. This results in focal demyelination with relative axonal sparing. This would account for the development of optic neuritis. Which affects the sight, this explains blurred vision and loss of vision for the patient. The best evidence for inflammation-induced relapses is confirmed through diagnostic imaging; the most reliable diagnostic we can use when dealing with MS would be MRI. which demonstrates the association of relapses with gadolinium enhancement, so a dye is injected intravenously which is disruption of the blood brain barrier. The main pathologic hallmark of MS is the demyelinated plaque, which has specific histological and immunohistological characteristics depending on the activity of the disease. This is the main indicator to diagnose MS. There have been cases of MS and inflammation causing lesions which are benign. This is most common, in the early phases of the diesease. To diagnose MS, the other diagnostic test used aside from imaging would be simple blood work. The stress induced blood marker that helps indicate MS induced stress kinases is elf2a. This is produced through a simple lab. 

Research in Ms

Dr Chen, discussed the neurobiology of M.s and its mechanics. She discussed that MS is the auto immune inflammatory response to the myelin antigens. And that MS, represents activity in the central nervous system (CNS) . And she also talked a little bit about how MS affects the patient, not only physically but biologically as well. As we know many MS patients it isn't something that constantly affects the patient, but similar to many autoimmune diseases there are phases of remission, and disease known as flare ups. When MS flares up the central nervous system is directly affected,  the patient experiences increased fatigue of the arms and legs in some severe cases manifestations can include optic neuritis. And other manifestations can include inflammation in the colon IBD. And lupus. Unlike these other autoimmune diseases, MS causes demyelination and loss of oligodendrocytes as discussed by Dr Chen in her talk.  Relapses are fundamentally a manifestation of an inflammatory response occurring mostly in the white matter of the nervous system but also within myelin tracts in the gray matter. This results in focal demyelination with relative axonal sparing. This would account for the development of optic neuritis. Which affects the sight, this explains blurred vision and loss of vision for the patient. The best evidence for inflammation-induced relapses is confirmed through diagnostic imaging; the most reliable diagnostic we can use when dealing with MS would be MRI. which demonstrates the association of relapses with gadolinium enhancement, so a dye is injected intravenously which is disruption of the blood brain barrier. The main pathologic hallmark of MS is the demyelinated plaque, which has specific histological and immunohistological characteristics depending on the activity of the disease. This is the main indicator to diagnose MS. There have been cases of MS and inflammation causing lesions which are benign. This is most common, in the early phases of the diesease. To diagnose MS, the other diagnostic test used aside from imaging would be simple blood work. The stress induced blood marker that helps indicate MS induced stress kinases is elf2a. This is produced through a simple lab.

What if one day, you couldn’t remember anymore?

What if one day, you couldn’t remember anymore? Memories of family, life, love, identity, and education- all becoming more and more unfamiliar. The abilities to learn and remember are aspects of life that are utilized every single day, but are often taken for granted. In the United States, 1 in 9 people age 65 and older has Alzheimer’s dementia1. Alzheimer’s disease is a form of dementia that is characterized by neurodegeneration of the hippocampus, resulting in decline of memory, thinking, and reasoning skills. 

In order to determine what mechanisms are responsible for synapse degradation in the hippocampus, identification of the neural components that strengthen a synapse are crucial to proposing a treatment method. Long term potentiation is a form of synaptic plasticity that results in the strengthening of a synapse by an increase of postsynaptic density 95 (PSD95), which stabilizes synaptic changes in long term potentiation by increasing NMDA/AMPA receptors of excitatory synapses. Increases in PSD95 also result in dendritic spine growth, thus strengthening the excitatory synapse. In an individual with Alzheimer’s, hippocampal excitatory neurons undergo long term depression (LTD) by excessively decreasing PSD95, thus resulting in a weakened synapse. 

In the article, “Pin1 Binding to Phosphorylated PSD-95 Regulates the Number of Functional Excitatory Synapses”, Delgado et. al investigate the mechanisms responsible for the regulation of PSD-95 at synapses, and what implications such mechanisms may have on potential treatments for neurodegenerative diseases. Pin1 is an enzyme that is known for its involvement in diseases such as Alzheimer’s, leading to investigation of its involvement with PSD-95. Delgado et. al exhibit that phosphorylation of PSD95 allows Pin1 to bind and cause long term depression by decreasing dendritic PSD95 and number of functional excitatory synapses. Additionally, knocking out Pin1 showed an increase in size and number of post synaptic spines, which could imply a potential treatment for degenerative diseases such as Alzheimer’s.

It is important to note that Pin1 plays a role in multiple aspects of cellular functioning- particularly cell cycle regulation and survival. In “Inverse Correlation between Alzheimer’s Disease and Cancer”, Zablocka explains that Pin1 KO mice showed a resistance to cancer, however they displayed neurodegenerative Alzheimer's-like symptoms. This finding suggests that Pin1 has a crucial regulatory mechanism. Zablocka details that Pin1 is responsible for maintaining a trans-conformation of tau and APP neuronal proteins, which promote functional neuron activity. A cis-conformation of APP results in an increase of B-Amyloid, which is characteristic of Alzheimer’s dementia. Inducing overexpression of Pin1 in the KO mice resulted in a decreased level of B-Amyloid; thus concluding that Pin1 plays a significant role in neuronal regulatory mechanisms- despite its influence on PSD. The increase in number of synaptic spines as a result of Pin1 inhibition could be a result of lack of regulatory mechanisms within the neuron- not necessarily beneficial to the strengthening of synapses. 

Pin1’s role in LTD and LTP can be considered for treatment and regulation of neurodegeneration, given its implications on conformational changes which influence B-Amyloid; however, more detailed signaling cascades such as Pin1’s influence on Wnt signaling and beta-catenins can be further investigated to further target the mechanisms of neurodegeneration and LTP.

References:

https://link.springer.com/article/10.1007/s12035-021-02544-1

https://www.frontiersin.org/articles/10.3389/fnmol.2020.00010/full 

The Future of Spinal Cord Injury Rehabilitation

 The approach to researching spinal cord injuries and their treatments are way different than treatments in other tissues where cells have the ability to repair. After a spinal cord injury, axons of neurons become severed/demyelinated. There is little to no recovery of nervous tissue function and tissue degeneration is progressive. It is not that the neuron is incapable of neuroplasticity, rather it is prevented by its environment because the immune system initiates scar tissue formation around the contusion as a barrier to contain the injury. This makes it hard for axons to regenerate and communicate with each other. Li et al. used a nanofiber-hydrogel composite (NHC) to modulate inflammation after spinal cord injury in rodents. The article “‘Dancing Molecules’ Successfully Repair Severe Spinal Cord Injuries” by Northwestern discusses recent research conducted by Alvarez et al. These researchers have engineered an injectable therapy using nanofibers in rodent models similar to Li et al. It is a supramolecular peptide fibril scaffold that includes two peptide sequences: one sequence focuses on inflammation and scarring whereas the other sequence promotes blood vessel formation. This therapy mimics the natural environment around the spinal cord where the molecules within the nanofibers move or “dance” out of the supramolecular polymers to engage with cell receptors. Morris states “This is the first study in which researchers controlled the collective motion of molecules through changes in chemical structure to increase a therapeutic’s efficacy” (Northwestern). Alvarez et al. hypothesized that if the molecules are dancing around, the probability that the molecules will meet up with the receptors is increased. They found that the more the molecules moved, the more successful the therapy was in recovering function in the mouse whose lower body was paralyzed. After a single injection into the rodent spinal cord, the animal was able to walk after four weeks. Many implications can be inferred from this research. The life expectancy and quality of life of spinal cord injury patients would be increased. However, the most important implication is that the supramolecular motion studied by Alvarez et al. can not only be applied to spinal cord injury therapy, but also other therapies as well.

Works Cited

Morris, Amanda | By Amanda Morris. 'Dancing Molecules' Successfully Repair Severe Spinal Cord Injuries, 11 Nov. 2021, https://news.northwestern.edu/stories/2021/11/dancing-molecules-successfully-repair-severe-spinal-cord-injuries/. 

A Baby’s Circadian Rhythm

             All humans have very similar circadian rhythms, and we can adjust it based on our everyday lives. Most everyone’s circadian rhythms are to wake up in the daytime and sleep at night. Some sleep later than others and some earlier. If you work at night your circadian rhythm is different as you sleep in the daytime and is awake at night. Adolescences and teenagers have similar circadian rhythms as they got to wake up early to go to school for 8 hours and then study and then back to bed to wake up early again. But what about babies? Babies are unpredictable as they can sleep all day and cry all night or vice versa on a good day. But one’s thing for sure is that babies need plenty of rest. But how do they know that they need it?

            The fruit fly or the Drosophila melanogaster is one species that is studied the most when it comes to circadian rhythms due to their many different behavior outputs. The molecular clocks in the brain and fat body of control flies gradually grow out of phase with one another under free-running conditions (Fulgham et al., 2021). This can be seen in humans as well as babies grow out of their unique molecular clocks and start to mold their new clocks into what society has created for humans growing up.

            Sleep and development go hand in hand when it comes to babies and them growing. In fruit flies, the period of feeding rhythms tracks with molecular oscillations in central brain clocks cells, consistent with a primary role of the brain clock in dictating the time of feeding behavior (Fulgham et al., 2021).  This is the same with babies in which they have responsive feeding, which means responding to a baby’s hunger cues, rather than feeding on a set schedule (Ruggeri, 2022). 

 

References

Fulgham, C. V., Dreyer, A. P., Nasseri, A., Miller, A. N., Love, J., Martin, M. M., Jabr, D. A.,     Saurabh, S., & Cavanaugh, D. J. (2021). Central and Peripheral Clock Control of         Circadian Feeding Rhythms. Journal of Biological Rhythms, 36(6), 548-566.             https://doi:10.1177/07487304211045835

Ruggeri, A. (2022, February 8). The Science of Healthy Baby Sleep. BBC Future. Retrieved        March 4, 2022, from 

            https://www.bbc.com/future/article/20220131-the-science-of-safe-and-healthy-baby-sleep