Medicine and Health Sciences Commons^™

Cognitive And Neuroscientific Perspectives Of Healthy Ageing, Jon B. Prince, Helen L. Davis, Jane Tan, Katrina Muller-Townsend, Shaun Markovic, David M. G. Lewis, Brianne Hastie, Matthew B. Thompson, Peter D. Drummond, Hakuei Fujiyama, Hamid R. Sohrabi

Research outputs 2022 to 2026

With dementia incidence projected to escalate significantly within the next 25 years, the United Nations declared 2021–2030 the Decade of Healthy Ageing, emphasising cognition as a crucial element. As a leading discipline in cognition and ageing research, psychology is well-equipped to offer insights for translational research, clinical practice, and policy-making. In this comprehensive review, we discuss the current state of knowledge on age-related changes in cognition and psychological health. We discuss cognitive changes during ageing, including (a) heterogeneity in the rate, trajectory, and characteristics of decline experienced by older adults, (b) the role of cognitive reserve in age-related cognitive decline, …

Augmenting Hand And Arm Function For Persons With Hemiparesis, Brooke Stein, Susan Duff, Alison Mckenzie, Bailey Advincula, Isaac An, Annie Jeon, Casey Mcwilliam, Will Potter, Virginia Ruano, Paulina Vokulich, Audrey Howell, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

Background. Hand and arm dysfunction due to neural disorders significantly influences quality of life. Activity-based training has been found to improve function. These improvements could be augmented with transcutaneous spinal cord stimulation (tSCS) due to the modulatory effect it has on spinal and supraspinal networks. Objective. The primary aim is to determine if a 4-week training program will improve hand and arm function. The secondary aim is to determine if the addition of tSCS to a second 4-week training session will further improve function. Design. This is a pre-posttest, controlled trial for persons 10-75 years of age, >6 months post …

Assessing Brain Processing Deficits Using Neuropsychological And Vision-Specific Tests For Concussion, Brent A. Harper, Rahul Soangra

Physical Therapy Faculty Articles and Research

Introduction: Since verbal memory and visual processing transpire within analogous cerebral regions, this study assessed (i) if a visual function can predict verbal memory performance. It also hypothesized whether neurocognitive (e.g., ImPACT) tests focusing on the Visual Memory and Cognitive Efficacy Index will predict Verbal Memory scores and (ii) if vision metrics and age can identify individuals with a history of concussion. Finally, it also hypothesized that King–Devick and near point of convergence scores alongside age considerations will identify candidates with a prior reported history of concussion. Materials and methods: This observational cohort assessed 25 collegiate ice hockey players prior …

Dopamine Release Neuroenergetics In Mouse Striatal Slices, Msema Msackyi, Yuanxin Chen, Wangchen Tsering, Ninghan Wang, Hui Zhang

Department of Neuroscience Faculty Papers

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Dopamine (DA) neurons in the substantia nigra pars compacta, which have axonal projections to the dorsal striatum (dSTR), degenerate in PD. In contrast, DA neurons in the ventral tegmental area, with axonal projections to the ventral striatum, including the nucleus accumbens (NAcc) shell, are largely spared. This study aims to uncover the relative contributions of glycolysis and oxidative phosphorylation (OxPhos) to DA release in the striatum. We measured evoked DA release in mouse striatal brain slices using fast-scan cyclic voltammetry applied every two minutes. Blocking OxPhos resulted in a greater …

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …

Suboptimal Self-Reported Sleep Efficiency And Duration Are Associated With Faster Accumulation Of Brain Amyloid Beta In Cognitively Unimpaired Older Adults, Louise N. Pivac, Belinda M. Brown, Kelsey R. Sewell, James D. Doecke, Victor L. Villemagne, Vincent Doré, Michael Weinborn, Hamid R. Sohrabi, Samantha L. Gardener, Romola S. Bucks, Simon M. Laws, Kevin Taddei, Paul Maruff, Colin L. Masters, Christopher Rowe, Ralph N. Martins, Stephanie R. Rainey-Smith

Research outputs 2022 to 2026

INTRODUCTION: This study investigated whether self-reported sleep quality is associated with brain amyloid beta (AB) accumulation. METHODS: Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self-reported sleep data, and positron emission tomography-determined brain AB measured over a minimum of three time points (range 33.3–72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) 4 allele status, and time, adjusting for sex and baseline age. RESULTS: Sleep duration < 6 hours, in APOE 4 carriers, and sleep efficiency < 65%, in the whole sample and APOE 4 non-carriers, is associated with faster accumulation of brain AB. DISCUSSION: These findings suggest a role for self-reported suboptimal sleep efficiency and duration in the accumulation of Alzheimer's disease (AD) neuropathology in CU individuals. Additionally, poor sleep efficiency represents a potential route via which individuals at lower genetic risk may progress to preclinical AD. Highlights: In cognitively unimpaired older adults self-report sleep is associated with brain amyloid beta (AB) accumulation. Across sleep characteristics, this relationship differs by apolipoprotein E (APOE) genotype. Sleep duration < 6 hours is associated with faster brain AB accumulation in APOE 4 carriers. Sleep efficiency < 65% is associated with faster brain AB accumulation in APOE 4 non-carriers. Personalized sleep interventions should be studied for potential to slow AB accumulation.

The Australian Multidomain Approach To Reduce Dementia Risk By Protecting Brain Health With Lifestyle Intervention Study (Au-Arrow): A Study Protocol For A Single-Blind, Multi-Site, Randomized Controlled Trial, Samantha L. Gardener, Stephanie J. Fuller, Sharon L. Naismith, Laura Baker, Miia Kivipelto, Victor L. Villemagne, Stuart M. Grieve, Paul Yates, Stephanie R. Rainey-Smith, Juliana Chen, Belinda Thompson, Nicola J. Armstrong, Malika G. Fernando, Carolina B. Castro, Silochna Meghwar, Rema Raman, Andrew Gleason, Catriona Ireland, Roger Clarnette, Kaarin J. Anstey, Kevin Taddei, Manohar Garg, Hamid R. Sohrabi, Ralph N. Martins

Research outputs 2022 to 2026

INTRODUCTION: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. METHOD: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55–79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a …

Promoting Diverse Perspectives: Addressing Health Disparities Related To Alzheimer's And All Dementias, Gladys Maestre, Carl Hill, Percy Griffin, Stephen Hall, William Hu, Jason Flatt, Ganesh Babulal

School of Medicine Publications and Presentations

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14–16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day …

Automated Seizure Detection Based On State-Space Model Identification, Zhuo Wang, Michael Sperling, Dale Wyeth, Allon Guez

Department of Neuroscience Faculty Papers

In this study, we developed a machine learning model for automated seizure detection using system identification techniques on EEG recordings. System identification builds mathematical models from a time series signal and uses a small number of parameters to represent the entirety of time domain signal epochs. Such parameters were used as features for the classifiers in our study. We analyzed 69 seizure and 55 non-seizure recordings and an additional 10 continuous recordings from Thomas Jefferson University Hospital, alongside a larger dataset from the CHB-MIT database. By dividing EEGs into epochs (1 s, 2 s, 5 s, and 10 s) and …

Neural Correlates Of Fear Extinction: Investing The Impact Of Puberty And Sex In Children And Adolescents Through Neuroimaging, Sneha Bhargava, Clara Zundel, Samantha Ely, Carmen Carpenter, Reem Tamimi, Leah Gowatch, Mackenna Shampine, Emilie-Clare O'Mara, Jovan Jande, Shravya Chanamolu, Ahmad Almaat, Hilary Marusak

Medical Student Research Symposium

Fear-based disorders, including anxiety and posttraumatic stress disorder, are more prevalent in females than males. Steroid hormones (e.g., estradiol) are involved in fear extinction learning and later recall—a process implicated in the pathophysiology of fear-based disorders. Fear-based disorders commonly emerge during the transition from childhood to adolescence, a period marked by the onset of puberty and a natural increase of steroid hormones. Here, we examined the effects of puberty, sex, and their interaction on extinction recall and underlying neural circuitry in youth. Eighty-five youth (6-17 years, 46% female) completed a two-day Pavlovian fear extinction paradigm while undergoing functional magnetic resonance …

Epithelial And Mesenchymal Olfactory Stem Cells Gathered With Minimally-Invasive Micro-Brush, Tyler Petersen

Medical Student Research Symposium

Spinal cord injury (SCI) causes devastating lifestyle and financial consequences for the patient. Treatment strategies emphasize neuroprotection, but not regeneration. In this regard, stem cells are an innovative field of study that has the potential to regenerate neural tissue, thereby increasing a person’s ability to regain function. The purpose of this project is two-fold: to attain olfactory stem cells located in the nasal canal in a minimally-invasive way and to gather neural cells from the epithelium and mesenchymal cells in the lamina propria. Cells were gathered with sterile nasal micro-brushes, stored, and grown in flasks. After cells reached confluency, they …

Abdominal Wall Endometriosis In Cesarean Scar: A Case Report, Willbroad Kyejo, Brenda Moshi, Euphraim Massanga, Gregory Ntiyakunze, Miriam Mgonja, Munawar Kaguta, Ernest Mdachi

Obstetrics and Gynaecology, East Africa

Abdominal wall endometriosis refers to the presence of endometrial tissue within surgical scars, most commonly occurring following gynecological procedures such as cesarean sections. This case report presents a rare case of abdominal wall endometriosis in a cesarean scar. The patient, a 32-year-old woman with a history of two previous cesarean sections, presented with cyclic pain and swelling in the lower abdominal region. Physical examination revealed a tender, well-defined mass within the cesarean scar. Surgical excision of the mass was performed, and histopathological examination confirmed the presence of endometrial tissue. This case highlights the importance of considering abdominal wall endometriosis in …

The Role Of Diet And Gut Microbiota In Alzheimer’S Disease, D. M.Sithara Dissanayaka, Vijay Jayasena, Stephanie R. Rainey-Smith, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (A ) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer’s disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of A , the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut–brain axis …

Sex-Specific Negative Affect-Like Behaviour And Parabrachial Nucleus Activation Induced By Bnst Stimulation In Adult Mice With Adolescent Alcohol History, Lucas Albrechet-Souza, Chelsea R. Kasten, Natalia B. Bertagna, Tiffany A. Wills

School of Medicine Faculty Publications

Adolescent alcohol use is a strong predictor for the subsequent development of alcohol use disorders later in life. Additionally, adolescence is a critical period for the onset of affective disorders, which can contribute to problematic drinking behaviours and relapse, particularly in females. Previous studies from our laboratory have shown that exposure to adolescent intermittent ethanol (AIE) vapour alters glutamatergic transmission in the bed nucleus of the stria terminalis (BNST) and, when combined with adult stress, elicits sex-specific changes in glutamatergic plasticity and negative affect-like behaviours in mice. Building on these findings, the current work investigated whether BNST stimulation could substitute …

Ephrinb2 Knockdown In Cervical Spinal Cord Preserves Diaphragm Innervation In A Mutant Sod1 Mouse Model Of Als, Mark W. Urban, Brittany A. Charsar, Nicolette M. Heinsinger, Shashirekha S. Markandaiah, Lindsay Sprimont, Wei Zhou, Eric V. Brown, Nathan T. Henderson, Samantha J. Thomas, Biswarup Ghosh, Rachel E. Cain, Davide Trotti, Piera Pasinelli, Megan C. Wright, Matthew B. Dalva, Angelo C. Lepore

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via …

Development Of A Novel Covalently Bonded Conjugate Of Caprylic Acid Tripeptide (Isoleucine–Leucine–Aspartic Acid) For Wound-Compatible And Injectable Hydrogel To Accelerate Healing, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Jibao He, Song Hong

School of Medicine Faculty Publications

Third-degree burn injuries pose a significant health threat. Safer, easier-to-use, and more effective techniques are urgently needed for their treatment. We hypothesized that covalently bonded conjugates of fatty acids and tripeptides can form wound-compatible hydrogels that can accelerate healing. We first designed conjugated structures as fatty acid–aminoacid1–amonoacid2–aspartate amphiphiles (Cn acid–AA1–AA2–D), which were potentially capable of self-assembling into hydrogels according to the structure and properties of each moiety. We then generated 14 novel conjugates based on this design by using two Fmoc/tBu solid-phase peptide synthesis techniques; we verified their structures and purities through liquid chromatography with tandem mass spectrometry and nuclear …

Alzheimer’S Disease And Microorganisms: The Non-Coding Rnas Crosstalk, Hanieh Mohammadi-Pilehdarboni, Mohammad Shenagari, Farahnaz Joukar, Hamed Naziri, Fariborz Mansour-Ghanaei

Department of Neurology Faculty Papers

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in …

Emerging Perspectives Of Synaptic Biomarkers In Als And Ftd, Karthik Krishnamurthy, Raj Kumar Pradhan

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are debilitating neurodegenerative diseases with shared pathological features like transactive response DNA-binding protein of 43 kDa (TDP-43) inclusions and genetic mutations. Both diseases involve synaptic dysfunction, contributing to their clinical features. Synaptic biomarkers, representing proteins associated with synaptic function or structure, offer insights into disease mechanisms, progression, and treatment responses. These biomarkers can detect disease early, track its progression, and evaluate therapeutic efficacy. ALS is characterized by elevated neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) and blood, correlating with disease progression. TDP-43 is another key ALS biomarker, its mislocalization linked …

Changes In Sleep Effort Mediate Insomnia Severity In Older Adults Following Online Cognitive Behavioural Therapy, Yvonne Kutzer, Lisa Whitehead, Eimear Quigley, Mandy Stanley

Research outputs 2022 to 2026

Background

To examine treatment mechanisms of digitally delivered cognitive behavioural therapy for insomnia (CBT-I), this study assessed the mediating effects of dysfunctional beliefs, hyperarousal, locus of control, self-efficacy, sleep effort, and safety behaviours on self-reported insomnia severity in older adults before and following the completion of a self-guided, online CBT-I program.

Methods

The baseline and follow-up measurements were completed by 62 older adults (55 female, 89%). This was a two-condition within-participant design. Mediation analysis using a parallel mediation model was conducted using the MEMORE macro for repeated measure designs.

Results

Out of all the included mediator variables, only a reduction …

Editorial: Neurotoxins In Alzheimer's Disease And Other Dementias, Alexandre Henriques, Philippe L. L. Poindron, Binosha Fernando, Kevin N. Hascup

Research outputs 2022 to 2026

Alzheimer's disease (AD) and other dementias are neurodegenerative disorders characterized by a progressive decline in cognition and independence from activities of daily living. Dementia is multifactorial with numerous risk factors including age, genes, molecules, lifestyle, and environmental contributions to disease onset and progression. In recent years, an emerging focus on neurotoxins has added a new layer of complexity to our understanding of dementia. This editorial aims to discuss recent updates regarding the role of neurotoxins in the pathogenesis of dementia.

Fluid Biomarkers In Cerebral Amyloid Angiopathy, Seyed M. Savar, Bin Ma, Eugene Hone, Farzana Jahan, Shaun Markovic, Steve Pedrini, Soudabeh Shemehsavar, Vandhana Easwaran, Kevin Taddei, Samantha Gardener, Jasmeer P. Chhatwal, Ellis S. Van Etten, Matthias J. P. Van Osch, Daniel Clarke, Anastazija Gnjec, Mark A. Van Buchem, Marieke J. H. Wermer, Graeme J. Hankey, Steven M. Greenberg, Ralph N. Martins, Hamid R. Sohrabi

Research outputs 2022 to 2026

Cerebral amyloid angiopathy (CAA) is a type of cerebrovascular disorder characterised by the accumulation of amyloid within the leptomeninges and small/medium-sized cerebral blood vessels. Typically, cerebral haemorrhages are one of the first clinical manifestations of CAA, posing a considerable challenge to the timely diagnosis of CAA as the bleedings only occur during the later disease stages. Fluid biomarkers may change prior to imaging biomarkers, and therefore, they could be the future of CAA diagnosis. Additionally, they can be used as primary outcome markers in prospective clinical trials. Among fluid biomarkers, blood-based biomarkers offer a distinct advantage over cerebrospinal fluid biomarkers …

Excitatory Drive To Spinal Motoneurones Is Necessary For Serotonin To Modulate Motoneurone Excitability Via 5-Ht2 Receptors In Humans, Tyler T. Henderson, Janet L. Taylor, Jacob R. Thorstensen, Justin J. Kavanagh

Research outputs 2022 to 2026

Serotonin modulates corticospinal excitability, motoneurone firing rates and contractile strength via 5-HT2 receptors. However, the effects of these receptors on cortical and motoneurone excitability during voluntary contractions have not been explored in humans. Therefore, the purpose of this study was to investigate how 5-HT2 antagonism affects corticospinal and motoneuronal excitability with and without descending drive to motoneurones. Twelve individuals (aged 24 ± 4 years) participated in a double-blind, placebo-controlled, crossover study, whereby the 5-HT2 antagonist cyproheptadine was administered. Transcranial magnetic stimulation (TMS) was delivered to the motor cortex to produce motor evoked potentials (MEPs), and electrical stimulation at the cervicomedullary …

Predicting Neurodegeneration From Sleep Related Biofluid Changes, Yue Yang, Woojin S. Kim, Johannes C. Michaelian, Simon J. G. Lewis, Craig L. Phillips, Angela L. D'Rozario, Pratishtha Chatterjee, Ralph N. Martins, Ron Grunstein, Glenda M. Halliday, Sharon L. Naismith

Research outputs 2022 to 2026

Sleep-wake disturbances are common in neurodegenerative diseases and may occur years before the clinical diagnosis, potentially either representing an early stage of the disease itself or acting as a pathophysiological driver. Therefore, discovering biomarkers that identify individuals with sleep-wake disturbances who are at risk of developing neurodegenerative diseases will allow early diagnosis and intervention. Given the association between sleep and neurodegeneration, the most frequently analyzed fluid biomarkers in people with sleep-wake disturbances to date include those directly associated with neurodegeneration itself, such as neurofilament light chain, phosphorylated tau, amyloid-beta and alpha-synuclein. Abnormalities in these biomarkers in patients with sleep-wake disturbances …

Unveiling The Link Between Systemic Inflammation Markers And Cognitive Performance Among Older Adults In The Us: A Population-Based Study Using Nhanes 2011–2014 Data, Zheng Guo, Yulu Zheng, Jian Geng, Zhiyuan Wu, Tao Wei, Guangle Shan, Yahong Zhu, Yuanyuan Zheng, Xingang Li

Research outputs 2022 to 2026

Purpose: This study aimed to evaluate the association between systemic inflammation markers and cognitive performance among older US adults. Methods: This cross-sectional study assessed 3,632 older participants from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). The main analysis included participants aged over 60 years. Systemic inflammation markers were quantified by calculating the composite inflammation indicators from the blood routine count, and cognitive performance was assessed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, Animal Fluency test (AFT), and Digit Symbol Substitution test (DSST). Results: There were 2,743 individuals enrolled in the current analysis. The overall …

Neuropsychiatric Symptoms Of Dementia In Those With And Without A Recorded History Of Psychological Trauma: A Comparative Study From An Australian Dementia Support Service, Monica Cations, Mustafa Atee, Thomas Morris, Daniel Whiting

Research outputs 2022 to 2026

Objective: To compare the number and severity of neuropsychiatric symptoms (NPS) and associated caregiver distress between those with and without a noted history of psychological trauma among those referred to a specialised national dementia NPS support service. Methods: This was a 5-year retrospective observational study of records from the Dementia Support Australia NPS support service. NPS were reported by formal or informal caregivers at service entry using the Neuropsychiatric Inventory Nursing Home version or Questionnaire version. A history of psychological trauma was recorded in the person's social or medical history and/or endorsed as a contributor to NPS by a trained …

The Association Between Plasma Igg N-Glycosylation And Neonatal Hypoxic–Ischemic Encephalopathy: A Case-Control Study, Liangao Wang, Xinxia Lu, Meng Wang, Xuezhen Zhao, Peirui Li, Haitao Zhang, Qingtang Meng, Yujing Zhang, Yingjie Wang, Wei Wang, Long Ji, Haifeng Hou, Dong Li

Research outputs 2022 to 2026

Introduction: Hypoxic-ischemic encephalopathy (HIE) is one of severe neonatal brain injuries, resulting from inflammation and the immune response after perinatal hypoxia and ischemia. IgG N-glycosylation plays a crucial role in various inflammatory diseases through mediating the balance between anti-inflammatory and pro-inflammatory responses. This study aimed to explore the effect of IgG N-glycosylation on the development of HIE. Methods: This case-control study included 53 HIE patients and 57 control neonates. An ultrahigh-performance liquid chromatography (UPLC) method was used to determine the features of the plasma IgG N-glycans, by which 24 initial glycan peaks (GPs) were quantified. Multivariate logistic regression was used …

A Systematic Review Of Dementia Research Priorities, Manonita Ghosh, Pelden Chejor, Melanie Baker, Davina Porock

Research outputs 2022 to 2026

Introduction: Patient involvement is a critical component of dementia research priority-setting exercises to ensure that research benefits are relevant and acceptable to those who need the most. This systematic review synthesises research priorities and preferences identified by people living with dementia and their caregivers. Methods: Guided by Joanna Briggs Institute methodology, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, we conducted a systematic search in five electronic databases: CINAHL, Medline, PsycINFO, Web of Science and Scopus. The reference lists of the included studies were also manually searched. We combined quantitative and qualitative data for synthesis and descriptive thematic …

In Sickness And In Health-Type I Interferon And The Brain, Wei Cao

Journal Articles

Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms …

Elovanoid-N34 Modulates Txnrd1 Key In Protection Against Oxidative Stress-Related Diseases, Jorgelina M. Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, Pranab K. Mukherjee, Yuehan Feng, Jakob Vowinckel, Tobias Treiber, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

The thioredoxin (TXN) system is an NADPH + H+/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3. This …

Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino

Farber Institute for Neuroscience Faculty Papers

Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death …