Neurosciences Commons^™

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 …

Multi-Domain Interventions For Dementia Prevention–A Systematic Review, C. B. Castro, L. M. Costa, C. Max B. Dias, J. Chen, H. Hillebrandt, Samantha L. Gardener, B. M. Brown, R. L. Loo, M. L. Garg, Stephanie R. Rainey-Smith, Ralph N. Martins, Hamid R. Sohrabi

Research outputs 2022 to 2026

Objectives: There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may individually or collectively be undertaken to increase one’s odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia. Design, Setting and Participants: This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or …

Lbnp Reduces Cerebral Perfusion But Does Not Impact Executive Function, James Van Riesen

Electronic Thesis and Dissertation Repository

A growing body of literature has demonstrated that a single bout of aerobic exercise and/or hypercapnic manipulations increase cerebral blood flow (CBF) and are linked to a transient (i.e.,min) post-intervention executive function (EF) benefit. However, there are no direct studies examining whether a transient decrease in CBF elicits a post-intervention EF decrement. Accordingly, my thesis employed 10-min single bout manipulations of -30 mmHg and -50 mmHg lower-body negative pressure (LBNP) to determine whether a transient reduction in CBF impacts EF. LBNP was applied as it renders sub-atmospheric pressure to the lower limbs and redistributes blood from the upper to lower …

A Two-Sample Mendelian Randomization Study Of Atherosclerosis And Dementia, Qiaoyun Zhang, Guangheng Wu, Xiaoyu Zhang, Sheng Wang, Youxin Wang

Research outputs 2022 to 2026

The causality between atherosclerosis and dementia remains unclear. This study aimed to explore the causal effect of atherosclerosis related indicators on dementia risk based on two-sample Mendelian randomization (MR) using summary statistics of genome-wide association studies (GWASs). The inverse variance weighted (IVW) method was performed as the main analysis, supplemented by different sensitivity analyses. Suggestive evidence indicated that peripheral arterial disease (PAD) (odds ratio (OR): 0.864, 95% confidence interval (CI): 0.797–0.937), coronary atherosclerosis (CoAS) (OR: 0.927, 95% CI: 0.860–0.998) and atherosclerosis, excluding cerebral, coronary, and PAD (ATHSCLE) (OR: 0.812, 95% CI: 0.725–0.909) were inversely associated with the risk of AD. …

Effects Of Jaw Clenching And Mental Stress On Persistent Inward Currents Estimated By Two Different Methods, Ricardo N. O. Mesquita, Janet L. Taylor, Gabriel S. Trajano, Aleš Holobar, Basílio A. M. Gonçalves, Anthony J. Blazevich

Research outputs 2022 to 2026

Spinal motoneuron firing depends greatly on persistent inward currents (PICs), which in turn are facilitated by the neuromodulators serotonin and noradrenaline. The aim of this study was to determine whether jaw clenching (JC) and mental stress (MS), which may increase neuromodulator release, facilitate PICs in human motoneurons. The paired motor unit (MU) technique was used to estimate PIC contribution to motoneuron firing. Surface electromyograms were collected using a 32-channel matrix on gastrocnemius medialis (GM) during voluntary, ramp, plantar flexor contractions. MU discharges were identified, and delta frequency ( F), a measure of recruitment–derecruitment hysteresis, was calculated. Additionally, another technique was …

Prevalent Distribution Of Conscious Processes On Either Side Of The Brain, Sohail Adnan, Mubasher Shah, Muhammad Fateen Rashed, Sadaf Nawab

Journal of Mind and Medical Sciences

Objectives. The brain has an intrinsic tendency for the lateralization of its functions. For instance, the left hemisphere assists in the comprehension and motor expression of language. What remains uncertain is whether conscious processes are also more prevalent in one hemisphere of the brain than the other. The epistemic goal of this research was to address this particular issue. Materials and Methods. We observed the rare pathological event of proximal occlusion of the middle cerebral artery (MCA), which halts blood flow to the central two-thirds of a hemisphere, and examined its effects on consciousness. We aggregated individual scores for eyes-opening …

Maxsim: Multi-Angle-Crossing Structured Illumination Microscopy With Height-Controlled Mirror For 3d Topological Mapping Of Live Cells, Pedro Felipe Gardeazabal Rodriguez, Yigal Lilach, Abhijit Ambegaonkar, Teresa Vitali, Haani Jafri, Hae Won Sohn, Matthew B. Dalva, Susan Pierce, Inhee Chung

Department of Neuroscience Faculty Papers

Mapping 3D plasma membrane topology in live cells can bring unprecedented insights into cell biology. Widefield-based super-resolution methods such as 3D-structured illumination microscopy (3D-SIM) can achieve twice the axial ( ~ 300 nm) and lateral ( ~ 100 nm) resolution of widefield microscopy in real time in live cells. However, twice-resolution enhancement cannot sufficiently visualize nanoscale fine structures of the plasma membrane. Axial interferometry methods including fluorescence light interference contrast microscopy and its derivatives (e.g., scanning angle interference microscopy) can determine nanoscale axial locations of proteins on and near the plasma membrane. Thus, by combining super-resolution lateral imaging of 2D-SIM …

A Preliminary Timeline Of The Midbrain Development In The Monodelphis Domestica Animal Model, Ismael Perez, John L. Vandeberg, Mario Gil

Research Colloquium

Introduction: The Brazilian short-tailed opossum (Monodelphis Domestica) is an understudied animal model compared to the Mus musculus that has been identified as a perfect candidate to study neurodevelopment (Baggott, L. & Moore, H., 1990). What makes the Monodelphis Domestica a perfect specimen for neurodevelopment is that the embryo develops outside the pouch of the mother providing easy noninvasive access to track changes across different developmental stages (Mate et al., 1994).

Objective: The objective of the study is to compare the area and volume in the development of the Monodelphis’s midbrain across three different developmental stages. Our research is beneficial because …

Eeg Functional Connectivity In Infants At Elevated Familial Likelihood For Autism Spectrum Disorder, Christian O'Reilly, Scott Huberty, Stefon Van Noordt, James Desjardins, Nicky Wright, Julie Scorah, Sara Jane Webb, Mayada Elsabbagh, Basis Team

Publications

Background

Many studies have reported that autism spectrum disorder (ASD) is associated with atypical structural and functional connectivity. However, we know relatively little about the development of these differences in infancy.

Methods

We used a high-density electroencephalogram (EEG) dataset pooled from two independent infant sibling cohorts, to characterize such neurodevelopmental deviations during the first years of life. EEG was recorded at 6 and 12 months of age in infants at typical (N = 92) or elevated likelihood for ASD (N = 90), determined by the presence of an older sibling with ASD. We computed the functional connectivity between …

Dissecting The Daily Feeding Pattern: Peripheral Clock/Cycle Generate The Feeding/Fasting Episodes And Neuronal Molecular Clocks Synchronize Them, Akiko Maruko, Koichi M Iijima, Kanae Ando

Department of Neuroscience Faculty Papers

A 24-h rhythm of feeding behavior, or synchronized feeding/fasting episodes during the day, is crucial for survival. Internal clocks and light input regulate rhythmic behaviors, but how they generate feeding rhythms is not fully understood. Here we aimed to dissect the molecular pathways that generate daily feeding patterns. By measuring the semidiurnal amount of food ingested by single flies, we demonstrate that the generation of feeding rhythms under light:dark conditions requires quasimodo (qsm) but not molecular clocks. Under constant darkness, rhythmic feeding patterns consist of two components: CLOCK (CLK) in digestive/metabolic tissues generating feeding/fasting episodes, and the …

The Influence Of Baseline Sleep On Exercise-Induced Cognitive Change In Cognitively Unimpaired Older Adults: A Randomised Clinical Trial, Kelsey R. Sewell, Stephanie R. Rainey-Smith, Jeremiah Peiffer, Hamid R. Sohrabi, James Doecke, Natalie J. Frost, Shaun J. Markovic, Kirk Erickson, Belinda M. Brown

Research outputs 2022 to 2026

Objectives: Observational studies consistently demonstrate that physical activity is associated with elevated cognitive function, however, there remains significant heterogeneity in cognitive outcomes from randomized exercise interventions. Individual variation in sleep behaviours may be a source of variability in the effectiveness of exercise-induced cognitive change, however this has not yet been investigated. The current study aimed to (1) investigate the influence of a 6-month exercise intervention on sleep, assessed pre- and post-intervention and, (2) investigate whether baseline sleep measures moderate exercise-induced cognitive changes. Methods: We utilised data from the Intense Physical Activity and Cognition (IPAC) study (n = 89), a 6-month …

Chromosomal Aberrations In Pediatric Patients With Moderate/Severe Developmental Delay/Intellectual Disability With Abundant Phenotypic Heterogeneities: A Single-Center Study, Dan Wu, Yi Wu, Yulong Lan, Shaocong Lan, Zhiwei Zhong, Duo Li, Zexin Zheng, Hongwu Wang, Lian Ma

Research outputs 2022 to 2026

Background: This study aimed to examine the clinical usefulness of chromosome microarray (CMA) for selective implementation in patients with unexplained moderate or severe developmental delay/intellectual disability (DD/ID) and/or combined with different dysphonic features in the Han Chinese population. Methods: We retrospectively analyzed data on 122 pediatric patients with unexplained isolated moderate/severe DD/ID with or without autism spectrum disorders, epilepsy, dystonia, and congenital abnormalities from a single-center neurorehabilitation clinic in southern China. Results: A total of 46 probands (37.7%) had abnormal CMA results among the 122 study patients. With the exclusion of aneuploidies, uniparental disomies, and multiple homozygotes, 37 patients harbored …

The Role Of Zinc In Psd-95 Palmitoyl Modification, Luis F. Acosta, Lili Guerra, Safiya Syed, Ivonn Ruvalcaba, Yonghong Zhang, Xiaoqian Fang

Research Symposium

Postsynaptic density-95 (PSD-95) is a membrane-associated guanylate kinase that mediates localization of receptors in the excitatory postsynaptic density. It has been reported that PSD-95 mediates postsynaptic localization of NMDA receptors and anchors postsynaptic AMPAR receptors mainly through its postsynaptic membrane targeting by its N-terminal palmitoylation. Recent studies have shown that Ca2+/calmodulin blocks palmitoylation of PSD-95 by binding at the N-terminus of PSD-95, which promotes dissociation of PSD-95 from the postsynaptic membrane and causes loss of surface AMPARs in cultured neurons. Another metal ion zinc is found in various areas of the brain. As an endogenous neuromodulator, zinc plays a role …

Fornix Volumetric Increase During Aging Associates To Microglia Activation Leading To Defective Cognitive Performance, Marcela Cárdenas Tueme, Luis Ángel Trujillo-Villarreal, Victor Ramírez-Amaya, Eduardo Garza-Villarreal, Alberto Camacho-Morales, Diana Reséndez-Pérez

Research Symposium

Background: Ageing displays a low-grade pro-inflammatory profile in blood and brain. It has been documented proinflammatory cytokines accumulation leading to neuroinflammation during aging. Aged brains integrate pro inflammatory cytokines accumulation, active microglia and volumetric changes which correlates with defective cognitive performance and neurodegeneration.

Methods: Mice from 2-,12- and 20-months-old of age were submitted to different memory tests: Y-maze, Barnes maze, object location test and object location test. Afterwards, we performed structural MRI to evaluate macrostructural changes related to memory and learning regions. Following this, we also evaluated in peripheral blood and in brain tissue the presence of pro-inflammatory cytokines …

Years Of Education And Total Intracranial Volume: A Longitudinal Study, Okechukwu C. Erinne

Research Symposium

Background: Education is one of the factors that contribute to a higher brain reserve. Based on the brain reserve hypothesis, the greater the brain reserve, the less likely it is to develop a neurocognitive disorder, such as dementia.

Methods: Data for this study were obtained from the Open Access Series of Imaging Studies (OASIS) longitudinal magnetic resonance imaging (MRI) data in nondemented and demented adults. There was a total of 150 right-handed participants and 373 imaging sessions, with an average duration of 719 days between visits. The primary outcome was estimated total intracranial volume (eTIV). Multivariable longitudinal regression was used …

Alzheimer’S Disease Studies In The Tex-Mex Border: Dissecting A Complex Multifactorial Problem, Ney Alliey-Rodriguez, Rosa V. Pirela, Alvaro Diaz-Badillo, Karla Lopez Lorenzo, Noe Garza, Frank Gilliam, Eron G. Manusov, Gladys E. Maestre

Research Symposium

Purpose: Alzheimer’s Disease (ALZ) is the leading cause of dementia in the aging population, and Latinos have >3 times higher risk to develop dementia than the overall US population. Although several studies have examined for possible causes of this increased risk, lack of comprehensive information plus a reduced number of Latino samples available in each study have hindered the answers.

Description: The University of Texas Rio Grande Valley has joined two large studies looking for multiple biomarkers associated with ALZ: The South Texas Alzheimer’s Center Clinical Data Repository and Biobank (STAC) and the Texas Alzheimer’s Research and Care Consortium (TARCC). …

Understanding The Resources, Barriers, Facilitators And Interests About Aging And Dementia Research Of Community Members From The Rio Grande Valley, Karla Daniela Lopez Lorenzo, Rosa V. Pirela Mavarez, Gabriela Osuna, Kendra Stine, Nahalie Chacon De Alvarez, Noe Garza, Gladys E. Maestre

Research Symposium

Background: One of ten people aged 65 develops Alzheimer’s Disease and it is one of the sixth-leading cause of death in the United States. The Rio Grande Valley (RGV) is mostly constituted by Hispanic/Latinos (93%), a population that has a 1.5X increased risk of AD onset. Nevertheless, there are not enough resources to support people living with dementia and their care partners. This study will leverage research efforts deployed by the RGV Alzheimer’s Disease Resource Center for Minority Aging Research to understand the social representations about the resources, barriers, facilitators, and interests of the RGV community about dementia and Alzheimer’s …

Comparing Stroke Symptom Recognition And Intervention Times In The Rio Grande Valley, Joshua M. Ninan, Kelsey Baker

Research Symposium

This is a retrospective study that aims to evaluate the duration from onset of stroke-like symptoms to presentation to medical facilities for aid in the Rio Grande Valley. The main goal of the study is to understand the extent of pre-hospital delays with regards to the treatment of stroke in the RGV.

Pro- And Anti-Inflammatory Biomarkers As Predictors Of Response To Valproate In Patients With Comorbid Alcohol Use And Bipolar Disorder-Preliminary Findings, Ilya Blokhin, Lisa Harlow, Eleonore Beurel, Feng Miao, Dana Ascherman, Claes Wahlestedt, Ihsan Salloum

Research Symposium

Objective/Hypothesis: Bipolar disorder (BD) has the highest association with alcohol and other substance use disorders compared to other major psychiatric disorders. This patient population is particularly challenging to treat. We have previously shown that some patients with co-occurring alcohol use and bipolar disorders respond to the GABAergic agonist valproate (VPA), which is known to modulates the dopaminergic system, and also as an epigenetic modifier. Predictors of therapeutic response to VPA in patients with AUD/BD are not known, and the subgroup which would benefit from VPA is still to be identified. Recent evidence suggests that AUD promotes a pro-inflammatory state while …

Can Alternative Medical Methods Evoke Neuro-Functional Somatosensory Responses? A Case Study Suggesting Functional Improvement, Alhasn Otaif, Mashan E. Alshammari, Christine G. Gerin

Research Symposium

Somatosensory pathways act as the avenue in transferring information concerning the body and its interaction with the external environment to the brain. We aim to demonstrate that through studying somatosensory, motor cortical and subcortical networks, we can explain functional recovery after stimulations applied as an alternative medical treatment. Those stimulations might have evidenced neural pathways and networks important in recovery of function. Materials and methods: The de-identified medical reports of nine patients with initial presentations of cerebral trauma or stroke inducing paralysis were studied.These included the alternative treatments they received and other available materials such as videos and photographs. Patients …