Why have there not been any cures for oligodendrocyte-related diseases?

 I had the privilege to attend a neuroscience seminar where Dr. Yanan Chen spoke about her research on Pelizaeus-Merzbacher Disease and oligodendrocyte survival. Due to my interest regarding the topic of hypomyelinated neuronal diseases, I made the decision to research and learn more about it and discuss my findings. Because there is little to be known about the direct causes of Multiple Sclerosis and, therefore, finding a cure, I find it interesting to learn about other similar diseases, such as PMD, that affect the myelination process. Dr. Chen’s research and other studies, however, are changing this by showing possible solutions or resistance therapies to these diseases. 

Before presenting her findings and research during the NEUR 300 seminar, Dr. Yanan Chen presented a study that shows how Pelizaeus-Merzbacher Disease negatively impacts the survival of oligodendrocytes and how integrated stress response inhibitors can aid in preserving the oligodendrocytes’ survival, despite the effects of PMD. They focused mainly on the male PMD mouse model Jimpy to “determine the impact of integrated stress response (ISR) on the oligodendrocyte response to mutant PLP expression” (Chen 2025). The study found that when the ISR-triggering eukaryotic initiation factor (eIF) 2α kinase was successfully inactivated, this process correlates with the survival of oligodendrocytes and myelination in the CNS. 

I became interested in this particular study because, when doing my own research, I found that I knew from previous research and courses at Loyola University Chicago that Multiple Sclerosis was a similar disease in the sense that it involves hypomyelination of axons, and therefore, I was wondering why there was not a cure yet found for either disease. I found a supplementary study by Doghish, Elazazy, Mohamed, Mansour, Ghanem et al. (2023), that describes how miRNAs could possibly play a significant role in Multiple Sclerosis "pathogenesis, diagnosis, and therapeutic resistance", and I was immediately intrigued (Doghish 2023). The study revealed that the diagnosis of Multiple Sclerosis was difficult “due to the lack of disease-specific biomarkers” and therefore, depends on ruling out numerous disabilities (Doghish 2023). Because of this, the researchers hope to further study “biological features of miRNAs in MS and explore their potential as a therapeutic target” (Doghish 2023). 

When reviewed as a whole, these investigations only provide a broad and hopeful conclusion to the problem, however, more research and findings must be done to provide a convincing conclusion overall. While Dr. Chen showed that the ISR-triggering eukaryotic initiation factor (eIF) 2α kinase was completely non-functioning, the survival of the oligodendrocytes and myelination of the CNS increased, Doghish, Elazazy, Mohamed, Mansour, Ghanem et al. (2023) showed that there is much to be revealed in the future regarding the future of miRNAs in multiple aspects of MS. These new discoveries and sciences may be used to treat not only PMD and MS, but also, provide a different approach to diagnosing and treating diseases involving the structure and functionality of the CNS. Together, these investigations reveal a bridge between neurological understandings and discussion, and therefore, provide hope for the future of curing uncurable diseases. 

 

References: 

Chen, Y., Kunjamma, R.B., Lin, K. et al. Integrated stress response inhibition prolongs the  lifespan of a Pelizaeus-Merzbacher disease mouse model by increasing  oligodendrocyte survival. Nat Commun (2025). https://doi.org/10.1038/s41467- 025-68045-0  

Doghish, Ahmed S, et al. “The Role of MiRNAs in Multiple Sclerosis Pathogenesis,  Diagnosis, and Therapeutic Resistance.” Pathology, Research and Practice, vol.  251, 1 Nov. 2023, pp. 154880–154880, https://doi.org/10.1016/j.prp.2023.154880.  Accessed 19 Apr. 2024. 

Nature and Nurture in Neurohealth

Today, people rely on their 5 senses to see the beauty of nature and life. The sense of sound is essential in listening to music, people, and the world around them to be able to make everlasting memories. Sound is, however, more than mere hearing; it is the precursor to overall health and function of the brain. What if auditory processing can be identified for neurological health in people whether genetically or man?

 Not long ago I had the opportunity to listen to Dr. She worked to determine whether concussions could be identified in children through brain responses to sound. Krizman’s research on concussions was aimed at identifying if brain responses to sound were identification of concussions in children (Krizman, 2023) by studying fundamental frequency (FO), “also known as the pitch cue”, and the frequency following response (FFR) and its effects on auditory processing following a concussion. One of the first observations was the effect of concussions on neural timing. A concussion therefore hampers the coordinated firing of neurons, which constitutes sound encoding. Brain responses are desynchronized, signals are dispersed, and arranged electrophysiological potentials of pitch have reduced efficacy. Finally, in those who have had a concussion, the auditory brainstem encoding of sound was tested by looking at FFR. There was a weakening of the F0 pitch, reduction of the response, and less accurate tracking of the sound in response to stimuli. In summary, concussions have adverse effects on the subcortical encoding of information, and this understanding can be a focal point in identifying injury or recovery.

A Neuroscience-based research study I came across, “Neural coding of formant-exaggerated speech and nonspeech in children with and without autism spectrum disorders” by Chen et al. Specifically, the TD children and children with ASD underwent testing of neurophysiological encoding of speech sounds at the neural level through a mechanism known as the frequency following response (FFR). The first conclusion was that children with ASD lacked automatic neural enhancement of exaggerating their speech compared to TD children. An exaggerated speech in TD children resulted in a better neural response, and the brainstem response was more accurate than in children with ASD whose neural response did not increase significantly and there was no brainstem response to enhancement. This reflects the influence on the cortex, which normally makes for its enhancement towards the brainstem responses to meaningful speech. In ASD children, the lack of enhancement meant speech was neurologically prioritized differently than in TD children. Finally, this can have a downside effect on the language development of children with ASD. From the neural differences, research can point towards early sensory contributions to language and differences in communication when it comes to autism.

While Dr. Krizman’s study focused on an injury and Dr. Chen’s was developmental, both studies demonstrated how the auditory system can be susceptible to disruption in the brain, leaving speech processing vulnerable. In concussed children, there was delayed neural timing in the brainstem that affected the encoding of speech, and in ASD children, their exaggerated speech was not able to lead to the neural enhancement experienced by TD children due to their altered use of the cortex. Ultimately, this shows a neurodevelopment comparison to neurotrauma and its effects in areas of the brain, leading to implications. This can then potentially be used to catch indicators of neurological health

Kraus, N., Thompson, E. C., Krizman, J., Cook, K., White-Schwoch, T., & LaBella, C. R. (2016). Auditory biological marker of concussion in children. Scientific Reports, 6(1). https://doi.org/10.1038/srep39009

Chen, F., Zhang, H., Ding, H., Wang, S., Peng, G., & Zhang, Y. (2021). Neural coding of formant‐exaggerated speech and nonspeech in children with and without autism spectrum disorders. Autism Research, 14(7), 1357–1374. https://doi.org/10.1002/aur.2509

The Hidden Impact of Concussions

A concussion is often characterized as a temporary brain injury associated with headache, dizziness and memory problems; however emerging neuroscience research has suggested that it has evident effects on the brain's ability to process sound and speech, extending beyond the anticipated symptoms. More specifically, causing difficulty in listening and communicating which possesses the question if hidden symptoms of brain injuries and often explained away by fatigue and distraction?

A few weeks ago I had the opportunity to listen to Jennifer Krizman’s presentation on the auditory biological markers of concussion in children, where she discussed how concussions impact the way the brain processes speech. She studied frequency following response, which captures how accurately the brain responds to sound. Her presentation and emergent dissolves suggest that concussion can have a more significant effect on the sensory processing system compared to traditional symptom-dependent diagnoses. 

Similar findings are studied in a recent study tilted Persistent post-concussion symptoms include neural auditory processing in young children which explained how concussions influence auditory processing after initial symptoms seem to improve. The researchers found that children with concussions have weaker neural encoding of speech sounds, specifically for pitch-related cues which are integral in unders†ådning everyday speech. These findings support Kriman’s idea that the effect of concussion can still be present in the brain after symptoms seem to improve, which indicates recovery can not be solely judged by symptom reports.

How Hands Help and Hurt

 When we think about learning, we usually focus on what is said. We assume that words carry the meaning and that gestures are just extra movement. But research in cognitive science suggests that our hands may play a much larger role in comprehension and memory than we realize. Research in cognitive science shows your hands shape, meaning, and memory. Gesture shifts comprehension. Gesture also disrupts comprehension. Natalia Zielinski and Elizabeth Wakefield tested this in 2021. They studied Polish-English bilingual children. They asked one question. Do gestures help more when language feels harder? 

Children watched stories in English and Polish. English served as stronger language. Polish served as weaker language. The storyteller used two gesture types. Matching gestures reinforced speech. Mismatching gestures added unstated details. Researchers tracked eye movement. They measured recall after each story. The results showed patterns. Children recalled more when matching gestures paired with weaker language. They looked at their hands more during weaker language. Gestures worked as support. When speech strained processing, children shifted attention to visual input. Mismatching gestures failed to help. Some reduced accuracy. 

Nicole Dargue found similar effects. Gestures aligned with speech improved comprehension. Gestures misaligned increased cognitive load. Cognitive load drives this pattern. Working memory holds limited information. Adults store about four chunks at once. Second language processing consumes capacity. Matching gestures distribute information across visual and verbal systems. Mismatching gestures demand integration of extra content. Capacity overload reduces recall. 

Zielinski’s eye-tracking data explains the mechanism. Attention shifts are based on difficulty. Gesture helps when you allocate focus. Gesture fails when attention splits. 

When you teach or present, do your hands mirror your words? Or do they introduce new content? In bilingual classrooms, gesture choice shapes equity. Students learning in a weaker language benefit from aligned visual cues. Extra motion without alignment strains memory. 

You communicate every day. When content grows complex, where do your eyes move? 
When you speak, do your gestures support your message or compete with it? 

References

Dargue, N., & Sweller, N. (2020). Learning stories through gesture: Gesture’s effects on child and adult narrative comprehension. Educational Psychology Review, 32(1), 249–276.

https://doi.org/10.1016/j.ridd.2021.104000

Zielinski, N., & Wakefield, E. M. (2021). Language proficiency impacts the benefits of co-speech gesture for narrative understanding through a visual attention mechanism. Proceedings of the Annual Meeting of the Cognitive Science Society, 43.

(02.03.26) - Elizabeth Wakefield - OneDrive 

 

Fundamental Frequency of Sound as Unique Animal Communication

 

Human auditory perception is so complex that we have the ability to distinguish people based on the slightest differences in their voice. The differences go beyond just pitch or volume, and many people use the word "color" to describe the specific tonal specialty of an individual, whether they are singing or simply talking. This "color" is what makes us instantly turn when hearing someone we know instead of lumping all background voices together. This "color" has a technical term; fundamental frequency, or F0, and this determines the uniqueness of human voice, and also, animals 'voices' too.

The paper "Auditory biological marker of concussion in children" by Nina Kraus et. al. relates fundamental frequency and other aspects of auditory processing to how brain damages experienced after a concussion. By comparing graphs of auditory perception from an individual pre and post traumatic brain injury, it can be determined whether damage has been done from said injury and whether it is to the extent of a concussion. Since concussions have no acute diagnostic test, being able to observe damage in this way could be a very beneficial diagnostic tool. Fundamental frequency, then, is a highly complex and special feature of auditory production and processing.

Furthermore, Kraus et. al. states that "tracking the F0 facilitates pitch perception, identifying sounds and talkers, and understanding stress and prosody," (Kraus, 2016) so not only is our processing of F0 useful for identifying the owner of a sound, but also what to interpret from the sound, on a very subtle level. This could mean that outside of intentional tone used by an individual when speaking, the very F0 of their voice could dictate some level of tonal perception as well. Maybe some fundamental frequencies innately have an off-putting expression, and some are more calming and inviting. This could be an explanation for certain "vibes" people may put off when they speak, an intangible perception others receive audibly that affects how they perceive the person as a result.

Humans are not the only creatures who have a fundamental frequency of sound, but animals do as well. They communicate in their own ways and can probably distinguish members of their species similarly to how humans do. However, there is one animal who has an extra layer of uniqueness to their fundamental frequency and sound they produce, and that is the horse. Horses have long been known to have a unique sound when they whinny, but now it is understood how; in one sound, horses produce two fundamental frequencies. There is a low-pitched sound from vibrating the larynx, like when humans sing, and simultaneously there is a high-pitched whistling from the vocal cords, unusual to most large animals. In a statement to Scientific American by co-author of the paper that discusses these findings, Élodie Briefer says “In the past, we found that these two frequencies are important for horses, as they convey different messages about the horses’ own emotions,” (Briefer, 2026). I think it is interesting that horses are one animal that has evolved to have two separate mechanics of sound production. There are birds for example that can produce two separate whistle sounds simultaneously, but they come from the same system, unlike the whistling and vibration patterns of a horse's whinny.

Both the paper by Kraus et. al. and the study about horses illustrate a unique auditory concept, fundamental frequency, and show how it has great value among humans as well as other animals. of sound. The findings about horses and how their F0 is a factor in their emotional communication could provide insight into how F0 conveys emotion and tone, and this could translate into human communication as well. Fundamental frequency is an evolutionarily conserved mechanism for communication in specifying certain things, like owner and pitch, but there is something extra special about the way horses have evolved with it, allowing them to produce multiple F0s through different mechanisms. I am interested to see where these findings take scientists in the fields of neuroscience, auditory mechanisms, and human and animals processes.

 

References:

Kraus, Nina et. al. 2016. Auditory biological marker of concussion in children. Scientific Report retrieved from Nature.com

Mogensen, Jackie Flynn. “Horses Whinny by Making Sounds in a Unique Way That Is Not Seen in Other Animals.” Scientific American, Scientific American, 25 Feb. 2026, www.scientificamerican.com/article/how-horses-whinny-has-long-been-a-mystery-now-scientists-think-they-know-the/.

Potential Drug Suppresses a Key Hallmark of Alzheimers

    

Potential Drug Suppresses a Key Hallmark of Alzheimers     

The loss of synaptic connections is a key predictor of Alzheimer's disease. This irreversible neurodegenerative brain disorder destroys memory and thinking, eventually destroying the ability to perform simple everyday tasks. Amyloid-β is a peptide that is especially prone to misfolding and aggregation, which abnormally accumulates in AD patients, initiating synaptic dysfunction. Synaptic loss and the accumulation of Aβ strongly correlate with impairment in AD, yet the mechanism linking the origin of this loss and the pattern it follows remains unclear. 

Upon taking Introduction to Neuroscience, I had an assignment in which I explored recent news about Alzheimer's disease. This study targeted arginine-Aβ in mice, how it accumulates early, drives inflammation, and precedes behavioral impairment. This past semester, I was able to listen to Dr. Delgado explain his research. In the study “Pin1 binding to phosphorylated PSD-95 regulates the number of functional excitatory synapses," Dr. Delgado and colleagues suggest a molecular mechanism by which the phosphorylation of PSD- 95, a postsynaptic density protein, recruits Pin-1 and decreases the number of functional synapses. When reading his research article, I began to understand the connection that can be made to findings I had previously read about.  

The study, "Oral administration of arginine suppresses Aβ pathology in animal models of Alzheimer’s disease," follows the study of a potential drug that can reverse aggregates present in Alzheimer's cases. The team evaluated Aβ, a key hallmark of Alzheimer's, in different animals carrying different mutations. Scientists tested the peptide to see if the drug, arginine, stops the accumulation of Aβ.  Findings from Kindai University suggest that reduced Aβ aggregation leads to less kinase overactivation. The less pathological phosphorylation leads to less Pin1 recruitment, and the preserved PSD- 95 maintains excitatory synapses. Aβ aggregation likely leads to the phosphorylation events that enable Pin1- mediated synaptic loss. The results were promising as both accumulation and toxicity were mitigated, as well as behavioral performance improvement and a reduction of neuroinflammation.

These findings lend support to a theory where incorrect phosphorylation signaling triggered by Aβ aggregation destabilizes postsynaptic scaffolding through Pin1and PSD-95 interactions, resulting in synapse loss. This synaptic loss may be reversed through interventions such as the drug arginine, which has shown to suppress aggregation and indirectly protect synapses by preventing activation of this destabilizing pathway. These findings open new possibilities for developing new strategies and treatments for neurodegenerative diseases. 

Together, these studies highlight how Alzheimer’s disease progression may be driven not only by the presence of amyloid-β, but by the molecular signaling cascades it initiates at the synapse. By linking Aβ aggregation to abnormal phosphorylation events that destabilize postsynaptic scaffolding through Pin1 and PSD-95, this work helps clarify how early synaptic loss emerges and spreads before widespread disease progression. Importantly, the ability of arginine to suppress Aβ aggregation and reduce downstream pathological signaling suggests that targeting early aggregation events may preserve synaptic integrity and slow cognitive decline. Because aggregations and protein misfolding are central to a great variety of neurodegenerative diseases, these findings can have broader applications beyond just Alzheimer’s. Together, these findings emphasize the value of combining molecular, synaptic, and behavioral approaches to better understand Alzheimer’s disease and to guide the development of disease-modifying therapies aimed at protecting synaptic connections, such as arginine.  Alzheimer’s breakthroughs bring us closer to slowing and reversing memory loss. It is compelling as these advances offer hope for protecting and preserving the moments that matter most.

References 

Delgado, J. Y.; et al. Pin1 Binding to Phosphorylated PSD-95 Regulates the Number of Functional Excitatory Synapses. Neurochemistry International 2025, 186, 105835. https://doi.org/10.1016/j.neuint.2025.105835

Fujii K, Takeuchi T, Fujino Y, Tanaka N, Fujino N, Takeda A, Minakawa EN, Nagai Y. Oral administration of arginine suppresses Aβ pathology in animal models of Alzheimer's disease. Neurochem Int. 2025 Dec;191:106082. doi: 10.1016/j.neuint.2025.106082. Epub 2025 Oct 30. PMID: 41175945.