12 noon Keynote
1:15-1:55 Student talks (virtual)
1:55-2:45 Student talks (in-person)
2:50-3:55 Poster Session
4:00-4:30 Grad Panel
4:30 NRP induction (Dr. Neuwirth and Dr. Phan)
Scientific Abstracts
Virtual Oral Presentation #1
[1:15pm-1:25pm]
Main Presenter: Kiyeon Chae
Department of Psychology, Rutgers University
Title: Corticotropin-releasing factor-expressing neurons in the bed nucleus of the stria terminalis reduces effort-related choice behaviors in mice
Abstract
The Bed Nucleus of the Stria Terminalis (BNST) is known to play a crucial role in stimulating hypothalamus-pituitary-adrenal (HPA) axis through corticotropin-releasing factor (CRF), which is released during body’s response to perceived stress. Prolonged CRF is related to the etiology of stress-related mental illnesses that show disruptions in the limbic system, a brain area that is known to modulate behaviors related to reward processing and learning. The BNST is predicted to have a complex valence surveillance role, where it regulates both positive and negative behaviors like reward-approaching and avoidance.
Virtual Oral Presentation #2
[1:25pm-1:35pm]
Main Presenter: Pehal Singh
Department of Psychology and SUNY Neuroscience Research Institute, SUNY Old Westbury
Title: The Effects of Neurodevelopmental Lead Exposure on the NeuwirthTM Holeboard Test
Abstract
Rodent models are the primary species for pre-clinical study and experimentation for biomedical translational research. However, subsequent testing on a variety of behavioral tests as a "battery" can often result in an extraneous variable of confounding carryover effects if not carefully considered. For example, if a more stressful test is used prior to a less stressful test, inflated and artifactual increases in the latter test may be considered real. Thus, care behavioral test sequences are critical to avoid these pre-clinical testing errors that may forestall promising drug candidates for clinical phase trials. In the present study, we examined the NeuwirthTM Holeboard test, which is designed to overcome these testing sequence confounds, by using the same testing apparatus over 2 days. In day 1, a 10 minute exploration trial is used to assess fear/escape behaviors. Then, 24 hrs later, 4 Petri Dishes with 4 different odors are placed below the apparatus to increase the rat's cognitive/exploratory behaviors and overcome both the prior day's anxiety-like behaviors and habituation over 2 days. We explored this testing procedure to evaluate the effects of neurodevelopmental lead exposure and how it may be a useful tool in parsing very subtle brain deficits through such a simple testing procedure. This is a pilot study that currently shows that the test can be used to determine both sex-dependent and developmental time-period differences in the rats behaviors. This testing procedure may have greater advantages for pre-clinical study that may further accelerate drug advancement to clinical phase trials.
Virtual Oral Presentation #3
[1:35pm-1:45pm]
Main Presenter: Benjamin Dursile
Department of Biology and SUNY Neuroscience Research Institute, SUNY Old Westbury
Title: An Assessment of Strain- And Visual Pigmentation-related Differences in Neurocognitive And Neurobehavioral Outcomes in the Transgenic Cohen’s Alzheimer’s Disease Rat Model
Abstract
The rates of Alzheimer’s Disease (AD) globally is expected to double by the year 2050, yet effective pre-clinical treatments for forestalling, recovering, and preventing AD symptoms are lagging. Pre-clinical research is critical for both early and later clinical phase trials, but drugs may be improperly moved forward as false positives when behavioral experimental controls or comparisons are either overlooked or lacking. Thus, these missteps can substantially delay advancement of drug candidates. The Cohen's Alzheimer's Disease (AD) rat pre-clinical model employs a Fischer 344 (F344) genetic background, but it unfortunately, is an albino rat, visually non-pigmented, and has poor visual acuity when compared to its pigmented counter-parts. Concerns arise when visually non-pigmented rat models are used for pre-clinical study, as they may have an artificially truncated or reduced cognitive capacity making them a less informative model for neurocognitive and neurobehavioral evaluations. To address this issue, the F344 AD rat model was crossed with a Long Evans (LE) visually pigmented rat model to produce a LE AD rat model. The rats’ behavioral performances were assessed on the Open Field (locomotor activity), the Elevated Plus Maze (anxiety-like behaviors), and the NeuwirthTM-Holeboard Test (fear/escape vs. cognitive/exploratory behaviors over 2 days). The data revealed that across all tests, female rats regardless of strain had increase locomotor activity, anxiety-like behaviors, and fear/escape and cognitive/exploratory behaviors. Across all tests the F344 AD rats had a lower bandwidth/range for the capacity of their behavioral deficits to be observed when compared to the LE AD rats. The findings show that if a cognitive enhancing drug and/or anxiety-like drug were to be used to treat AD through these rats in the pre-clinical testing phase that the LE AD rats would provide a more sensitive model for therapeutic assessment and showing a greater range of cognitive deficits and recovery.
Virtual Oral Presentation #4
[1:45pm-1:55pm]
Main Presenter: Geanelle R. Sam
Department of Biology and SUNY Neuroscience Research Institute, SUNY Old Westbury
Title: An Assessment of Taurine as a Nootropic in Aged Male Rats in The Attention Set-Shift Test
Abstract
The global population is continuing to age more than ever before, while at the same time increasing the rates of age-related cognitive dementias and associated neurodegenerative disorders. This situation has directed researchers to examine the potential for cognitive enhancing drugs to ameliorate or forestall the naturally occurring age-dependent decline in cognitive functions that accompanying aging. The present study examined in aged male rats (i.e., 1-year of age) that were randomly assigned to either a Control water of 0.05% Taurine water (i.e., for 1-month) prior to being subjected to the Neuwirth-BrownTM Attention Set-Shift Test (ASST; a very sensitive test for cognitive functions of the frontal lobes’ flexibility and evaluation of perseverative behaviors) and were compared to a group of young male rats (i.e., 3-4 months old). The Old Control rats unfortunately due to age-related cognitive impairments could either not complete simple discrimination training (66.67%) or the simple discrimination during test day 1 (33%). Interestingly, the age-matched Old Control+Taurine rats were able to complete the ASST training (i.e., faster latency) and testing (i.e., similar amount of trials to completion) at rates comparable to the Young Control rats. The data suggest that taurine (i.e., a GABA receptor agonist) serves as a nootropic (i.e., cognitive enhancing drug) in an aging rodent model through recovery of fronto-executive functional behaviors in the ASST with brain imaging evidence showing taurine-dependent increases in dopamine fluorescent tagged neurons in the olfactory bulbs and prefrontal cortical areas that regulate fronto-executive functions. It is thought that since aging reduces the level of GABA (i.e., the main inhibitory neurotransmitter in the brain) and less inhibition can result in impulsive decision making, that taurine may serve to compensate and replenish GABA levels in the aging brain, which in part, could explain the cognitive improvements in this animal model of aging. This work shows that taurine may prove to be an effective nootropic to be prescribed in aging populations to forestall cognitive dysfunctions in the elderly by increasing GABAergic tone and Dopaminergic signals underlying more regulated inhibition and motivation.
In-Person Oral Presentation #1
[1:55pm-2:05pm]
Main Presenter: Zoe Reich
Department of Molecular Biology and Biochemistry, Rutgers University
Title: Dissecting Fundamental Biology of Neuronal Aggregate Transfer in a Simple Alzheimer’s Disease Model
Abstract
One of the greatest challenges in medicine today is Alzheimer’s disease (AD), predicted to affect over 25 million Americans by 2050. A major recent finding in human neurodegenerative disease is that aggregated proteins like Amyloid Beta (Aβ₁₋₄₂) can spread among neurons and their support cells to promote pathology. My work models the transfer of neuronal aggregates and organelles via large membrane-bound vesicles called exophers in C. elegans, a novel model of neuronal trash management in which toxic material is handed off to neighboring cells for degradation. I hypothesize that knocking down homologs of AD associated risk genes in C. elegans may modulate exophergenesis and alter pathogenesis in the C. elegans AD model. By comparing AD risk genes identified by Genome Wide Association Studies of AD, I identified the C. elegans homologous genes of these AD risk factor genes. I am using RNAi approaches to knockdown the expression of these risk factor genes and testing for impact on C. elegans exophergenesis. I will present my data from this study and discuss implications for these loci in aggregate transfer biology.
In-Person Oral Presentation #2
[2:05pm-2:15pm]
Main Presenter: Shaili Soni
Department of Cell Biology and Neuroscience, Rutgers University
Title: The Molecular and Cellular Basis of Neurodegeneration in MARK2 Knockout Mice
Abstract
Alzheimer’s disease (AD) is a severe cause of disability in the older population, with cognitive and behavioral deficits contributing to a deterioration in quality of life. Characterized by amyloid beta (Ab) plaques and tau protein neurofibrillary tangles (NFTs), AD has several molecular indications intertwined to form a complex pathogenesis. Some of these additional molecular symptoms include transcriptional dysregulation, irregular autophagy, and anatomical neurodegeneration in hippocampal and cortical structures. The tau NFTs are a downstream result of tau hyperphosphorylation, which is known to be induced by the Par1/MARK family of proteins. Specifically, MARK2 is found to selectively phosphorylate the tau protein at Serine262/356, thereby initiating the hyperphosphorylation. Surprisingly, studies show that MARK2 expression is severely depleted in human AD brains, and MARK2-/- exhibit significant synaptic and behavioral deficits. This suggests that MARK2 plays a tau-independent role in contributing to AD-related neurodegeneration; however, the molecular mechanisms remain unclear. MARK2 is known to regulate other pathways, such as transcriptional regulation and autophagy. We hypothesize that loss of MARK2 contributes to neurodegeneration through regulation of pathways such as gene expression or autophagy.
In-Person Oral Presentation #3
[2:15pm-2:25pm]
Main Presenter: Praneet Paruchuri
Department of Cell Biology and Neuroscience, Rutgers University
Title: Nonnative States of Mutant Huntingtin Promote Inclusion Body Aggregation in a Huntington’s Disease Cell Model
Abstract
Age-dependent formation of insoluble protein aggregates is a key attribute among neurodegenerative diseases. We study the role of mutant huntingtin (mHtt) aggregation in Huntington’s Disease (HD), one that is characterized by intrinsically disordered proteins (IDP) and regions (IDR) in the poly-Q tract that manifest as chorea, cognitive, behavioral, and psychological deficits, and eventually death. However, it remains unclear the properties that drive the aggregation of mHtt out of the soluble form. Here, we induce a transient Cold Shock (CS) at 4°C with an immediate recovery temperature period of 37°C to show a significantly higher IB formation than the control and CS with no recovery. We find that the CS-induced IB formation is independent of Microtubule integrity and de-novo synthesis. The findings of this study indicate that the low temperature of cellular stress restricts the ability of the intrinsically disordered mHtt to adopt different conformations, leading to the formation of intermediate structures that are easily susceptible to de-solvation and hydrophobic interaction for the creation of inclusion bodies (IBs) at higher temperatures during recovery. These observations, coupled with our previous discoveries of how heat shock protein chaperones and osmolytes can stimulate mHtt IB formation, emphasize the importance of mHtt structural organization and rigidification, which plays a vital role in hydrogen bond-mediated cross-linking and a two-stage mechanism of mHtt IB formation in living cells.
In-Person Oral Presentation #4
[2:25pm-2:35pm]
Main Presenter: Mysore Sachin
Department of Life Sciences, Rutgers University
Title: Using Polyethylene Glycol to understand the fundamentals of Huntington's disease
Abstract
Huntington’s Disease is an inherited neurodegenerative disease which affects movement and cognition. A CAG trinucleotide repeat within the Huntingtin gene in chromosome 4 causes a pathological gain of function mutation of the Huntingtin protein (mHtt), that drives cell death, and bolsters propensity for aggregation from free form diffuse into solid precipitates called inclusion bodies. It has been postulated that free form diffuse mHtt is more culpable as the primary driver of cell death while the aggregated form acts more as a cellular coping mechanism, however, the roles of diffuse and aggregate mHtt in HD progression are not clear. We seek to understand what kind of cellular environment can push inclusion body formation so as to better comprehend the role of diffuse and aggregated mHtt in eventual neurodegeneration. From our previous research, we postulated that the structuring of mHtt can drive its aggregation within the cell. We hypothesize that cellular crowding via hyperosmotic stress can structure mHtt and drive aggregation. Using an inducible cell model, we found that Polyethylene Glycol can drive IB formation robustly in a concentration dependent manner. In addition, we tested various polymer lengths of PEG ranging from 600-3000 and found that PEG can drive aggregation to a greater extent with larger polymer lengths. We also found that inhibition of de-novo protein synthesis did not significantly affect IB/diffuse ratio, suggesting PEG does not indirectly influence aggregation via stress response pathways. These results, with the context of our previous research, support our hypothesis that Polyethylene glycol can structure and subsequently drive IB formation via cellular crowding. Further exploring this avenue can provide a more fundamental understanding of how mHtt behaves within the cell and how its propensity to aggregate can change with changes in the cellular environment.
In-Person Oral Presentation #5
[2:35pm-2:45pm]
Main Presenter: Syed Sarwar
Department of Cognitive Sciences, Rutgers University
Title: Development and perpetuation of biased beliefs concerning drug-related events among treatment-engaged individuals with Opioid Use Disorder
Abstract
Despite growing psychoeducational efforts and public messaging, people with opioid use disorder (OUD) often underestimate the risk for harm related to their drug use. Optimism bias, or the belief that good outcomes are more likely than bad ones, is a pervasive cognitive bias that influences how people process valenced information to inform their estimates of future outcomes. However, whether people hold a domain-specific optimism bias about drug use, and the factors that maintain this bias over time, remain unknown. To address these questions, we enrolled treatment-engaged individuals with OUD and matched healthy community controls in a 4-week smartphone-based ecological-momentary assessment study. Participants completed an initial optimism bias task in-person during which they estimated their risk of negative drug-related and nondrug-related outcomes (e.g., overdose, infection, injury), before and after receiving information about the actual base rates of these outcomes for someone in their demographic. Following the in-person session, participants completed self-report surveys probing affective states and a version of the optimism task on their own smartphones. During the initial session, we found that participants demonstrated an optimism bias, revising their estimates of future risk more after receiving desirable vs. undesirable information. Patients were more optimistic for drug-related outcomes compared to healthy controls. During the ecological-momentary assessment portion, we found that our sample overall was optimistic over time, with patients tending to become more optimistic for drug-related outcomes the longer they were enrolled in the study. Individuals with OUD hold biased beliefs about their drug use which are maintained and even strengthened as they engage in their natural environments. These findings highlight opportunities for improving psychoeducational interventions for substance use by considering the cognitive science of optimism.
In-Person Poster Presentation # 1
[2:50pm-2:57pm]
Main Presenter: Dhruvi Desai
Department of Psychology, Rutgers University
Title: Whole Brain Mapping of Pre-optic Area Inputs
Abstract
Substance use disorders lead to homeostatic dysregulation, which can alter pain processing and cause comorbidity with other mental health disorders. The lateral preoptic area has been shown to be involved in homeostasis, pain, and reward-seeking behaviors, however the nature of this involvement is unclear due to poor understanding of its connectivity. The goal of the present study was, therefore to investigate whole-brain afferent connections (i.e., inputs) to the lateral preoptic area using the anatomical tracer Fluorogold. Whole brain mapping of retrogradely labeled inputs was accomplished using the open-source SharcQ tool to create an unbiased, accurate cell-to-brain registration. From cases where Fluorogold injections were restricted to the preoptic area, we observed a high density of cells in specific cell groups of the hypothalamus, midbrain, amygdala, and thalamus. Among non-hypothalamic, long-range afferents to the preoptic area, we observed strong inputs from the periaqueductal gray, medial and central amygdalar nuclei, subparafascicular area, and tuberal nucleus. Overall, our data suggest the involvement of several brain regions in the lateral preoptic afferent circuity. Moreover, these data provide key insights into the functional connectivity of the lateral preoptic area, and will help us to better understand both the sources of types of information that support the various roles of the preoptic area in motivated behavior.
In-Person Poster Presentation #2
[2:58pm-3:05pm]
Main Presenter: Nicholas Panzera
Department of Cell Biology and Neuroscience, Rutgers University
Title: RIPK3 Modulates NMDAR-dependent Neuronal Death During Zika Virus i=Infection
Abstract
Receptor Interacting Protein Kinase-3 (RIPK3) is an enzyme commonly associated with the induction of necroptosis, a form of programmed cell death, in virally infected cells, that is vital to the innate immune response. In cells infected with Zika Virus (ZIKV), RIPK3 has been shown to coordinate the expression of key antiviral and immunological transcripts, in the absence of cell death. However, whether engagement of RIPK3 activation by ZIKV infection influences neurologic gene expression and neuronal function remains unexplored. In our previous work, transcriptomic profiling of primary cortical neurons infected with ZIKV and in vivo intracranial ZIKV infection of mice revealed that several key neurobiological pathways, including genes associated with the internalization and transport of glutamate neurotransmitter receptors, were regulated by RIPK3 in infected neurons. However, this dysregulation observed in infected Ripk3-/- neurons was not observed in uninfected Ripk3-/- neurons. These findings indicate that innate immune signaling via RIPK3 may play a previously unknown role in the regulation of neurotransmitter receptor internalization and transport. Recent evidence suggests that excitotoxic cell death is a major mechanism of neuropathogenesis during ZIKV infection, characterized by increased levels of extracellular glutamate and NMDAR-dependent increases to intracellular calcium levels. We suspect that the regulation of neurotransmitter receptor internalization and transport processes via RIPK3 is a contributing factor to the phenomenon of excitotoxic death experienced during a ZIKV infection. We observed that both neurons and mice lacking expression of RIPK3 are more prone to NMDAR-dependent excitotoxicity as well as increased extracellular glutamate present in infected neurons. We also have demonstrated that mice lacking the expression of RIPK3 are more susceptible to succumb pharmacologically induced seizure, providing further evidence of RIPK3’s role in the modulation of excitatory neurotransmission. Together, our results introduce a new possible route of RIPK3 signaling in the mediation of synaptic sensitivity during infection.
In-Person Poster Presentation #3
[3:06pm-3:13pm]
Main Presenter: Vincent Sotirov
Department of Psychology, Rutgers University
Title: Investigating The NOPR System via an Operant Conditioning Paradigm in Mice
Abstract
The nociceptin/orphanin FQ (NOP) receptor and its associated neuropeptide ligand are part of the opioid receptor family, though they exhibit different properties from classical opioid receptors. While the exact functions of the nociceptin opioid peptide receptor (NOPR) system are still being investigated, current literature suggests it plays a role in nociception (detection of painful stimuli), food intake, motor coordination, learning and memory, modulating immune function, and reward-seeking behavior.
In-Person Poster Presentation #4
[3:14pm-3:21pm]
Main Presenter: Maryam Khalid
Child Health Institute of New Jersey at Robert Wood Johnson Medical School, Rutgers University
Title: Phosphoproteome Validation of CC2D1A-deficient Hippocampal Cells in Mouse Model of Autism Spectrum Disorder
Abstract
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that widely affects communication, learning, and behavior. ASD is considered a spectrum due to the wide variety of the type & severity of symptoms. ASD & Intellectual Disability (ID) display a comorbidity that ranges between 30-50%, suggesting that there may be common genetic influence. CC2D1A (coiled-coil and C2 domain containing 1A) is a protein-coding gene that is one of hundreds of autosomal recessive genes found in ID. The protein CC2D1A has been found to be a positive regulator in the cAMP-PKA pathway in mouse hippocampus and cortex, achieved by repression of phosphodiesterase 4D (PDE4D). PDE4D regulates levels of cAMP, a secondary messenger that activates protein kinase A (PKA), allowing it to enter the nucleus and phosphorylate CREB at the Serine-133 location, leading to target gene transcription required for learning and memory. A new mouse model has been developed by creating a floxed CC2D1A allele for postnatal conditional removal of CC2D1A in the brain (excitatory neurons of cortex and hippocampus) using calcium/calmodulin-dependent protein kinase II-alpha (CamKIIa) promoter-driven Cre recombinase. This allows for viable & fertile mice with normal brain anatomy that demonstrate features of both cognitive & social impairment caused by the homozygous loss-of-function CC2D1A mutation seen in human ASD patients. This project aims to analyze mass spectrometry results of 8-week-old floxed-CC2D1A conditional knockout mice to produce a comprehensive analysis of protein and phosphorylation changes. Potential areas of interest include assessing sex differences in signaling & identifying which proteins can be impacted. After lysate preparation and Western blot analysis to validate genetic expression, liquid-chromatography-mass spectrometry (LC-MS/MS) was conducted on hippocampi retrieved from 8-week-old mice.
In-Person Poster Presentation #5
[3:22pm-3:29pm]
Main Presenter: Miaofan Chen
Department of Psychology and Cognitive Science, Rutgers University
Title: Building A Computational Model for Predicting 2-to 4-year-old Children's Cardinal Principal Knower Level Online
Abstract
Understanding the numerical acquisition process of children is crucial to comprehend their numerical reasoning abilities and future academic achievements. Under Covid-19 Pandemic, Dr. Alex Silver and her colleagues first ran the Point-to-X task on Lookit instead of only processing the Give-N Task to assess children’s knower-level – i.e., their understanding of the cardinal meanings of number words. However, the Point-to-X task does not assess the knower-level directly per se. Here we propose to make critical first steps in bridging this gap and reliably assessing knower-level online by building the Generative theory-based model and utilizing Silver’s dataset to validate our predicting model. The current predicting model can explain 19% of the variance in the Give-N task based on the performance in the Point-to-X task and suggests that 0-knowers have some number sense. We will hone the model by adding the noises in the future to find a better way of accessing the knower-level online.
In-Person Poster Presentation #6
[3:30pm-3:37pm]
Main Presenter: Annabel Guo
Department of Psychology, Rutgers University
Title: Effect of HDAC Inhibitors on Perineuronal Nets Formation in the Avian Auditory Cortex Following Song Exposure
Abstract
Epigenetic mechanisms and perineuronal nets (PNNs) have been shown to be involved in learning and memory. An important component of epigenetic regulation are histone deacetylases (HDACs), which are enzymes that remove histone acetyl groups and thus decrease transcription. HDAC inhibitors (HDACi), including RGFP966, block the HDACs from completing their function. PNNs are aggregations of chondroitin sulfate proteoglycans that dissolve in an activity- and/or experience-dependent manner and play a role in neural plasticity. The purpose of this study is to investigate whether epigenetic mechanisms, particularly HDACs, are involved in regulating genes that play an essential role in the formation and degradation of PNNs to control the amounts of auditory learning and memory formation in Zebra finch. Another objective involves investigating whether there is lateralization of function for encoding auditory memories due to PNN regulation. These objectives were studied by completing gene expression studies, in particular quantitative real-time polymerase chain reactions (qPCR), to quantify and compare levels of PNN-related gene expression. The results displayed that there were treatment differences in PNN-related gene expression with lower and higher gene expression of specific PNN formation-related genes and PNN degradation-related genes, respectively, in HDAC3i treated Zebra finches. The results also showed that rather than a leftward bias, there was a rightward bias in HDAC3i treated Zebra finches. This research is significant because it can be used to better understand whether HDAC3 can be a candidate molecular target in developing treatments to assist in auditory memory formation by affecting PNN regulation.
In-Person Poster Presentation #7
[3:38pm-3:45pm]
Main Presenter: Meghana Nampally
Department of Cell Biology & Neuroscience, Rutgers University
Title: Using the Retina as a New Chemogenetic Target to Treat Behavioral and Cognitive Symptoms of Alzheimer’s Disease
Abstract
Understanding the physiological pathways to memory and motivation is significant in treating and alleviating cognitive and behavioral symptoms caused by neurodegenerative disorders such as Alzheimer’s Disease (AD). Notably, during the early stages of Alzheimer’s Disease, the LC undergoes degeneration and is one of the first indicators of AD pathologies. Clinical evidence has also shown that the Locus Coeruleus (LC) plays an important role in arousal and memory; however, it remains unclear the exact neurophysiological mechanisms fundamental to these regulating these aspects of behavior and cognition.
In-Person Poster Presentation #8
[3:46pm-3:53pm]
Main Presenter: Myera Mian
Department of Cell Biology & Neuroscience, Rutgers University
Title: Effects of Cellular Milieu Aging on Protein Aggregation in Huntington's Disease
Abstract
Huntington’s Disease (HD), the most common autosomal dominant age-dependent neurodegenerative disorder (ND), is caused by an elongated CAG (glutamine) repeat within Exon 1 of the Huntingtin (Htt) gene. A ubiquitous feature of NDs is the aggregation of intrinsically disordered proteins, such as the formation of Inclusion Bodies (IBs) from the Htt protein in HD. It is suggested that IBs may occur due to the toxicity of soluble mutant Htt (mHtt). Considering that most NDs are age-dependent, this raises the question of how age can drive the aggregation of soluble intrinsically disordered proteins (IDPs). This literature review, in combination with our experimental data, serves to highlight what age dependent changes occur within the cellular environment and how they impact the aggregation of intrinsically disordered proteins. Additionally, we hypothesize that osmotic agents, which induce dehydration within the cell, result in molecular crowding, thereby increasing structuring of diffuse mHtt into IBs. Our current work illustrates that molecular crowding agents, such as polyethylene glycol (PEG), are able to significantly increase IB formation. These findings highlight that IB formation is dependent not only on the weight of the crowding agent used, but also upon its concentration. Moreover, the hydration state of the cell plays a vital role in promoting or hindering mHtt structuring, with a dehydration state favoring IB formation. Furthermore, in conjunction with other changes to the cell, such as ribosomal pausing, oxidative stress, and degradation of the ubiquitin-proteasome system and autophagy-lysosome pathway, it stands to reason that there are a multifaceted set of factors that contribute to the structuring of IDPs. These findings emphasize that understanding the impact of aging on protein structuring can elucidate potential therapeutics for not only HD, but many other age-dependent NDs.