Medical Neurobiology Commons^™

The Brainstem As A Conserved System For Consciousness: Integrating Phylogeny, Neurology, And Psychology, Shadia Kawkabani, Kevin P. Kaut

Journal of Neuropsychology and Behavioral Processes

Historically, scientists and physicians have taken a corticocentric view of consciousness, emphasizing the need for a cortex in producing the conscious experience. The preserved consciousness observed in hydranencephalic children and decorticated rats suggests that some form of consciousness may be produced by a subcortical network. The brainstem, a phylogenetically conserved brain system, could serve as the major integrative network to produce this form of consciousness—referred to as ‘affective consciousness’, the evolutionary antecedent to the reflective consciousness allowing humans to reflect on experiences. The functional integration of the brainstem with the amygdala, motor network, and other subcortical structures provides the architecture …

Pediatric Neurotropic Infection Alters Synaptic Development In The Developing Brain, Anuoluwapo Grace Fadare, Yashika S. Kamte, Manish N. Chandwani, Lauren A. O'Donnell

Rowan-Virtua Research Day

Many neurotropic viruses cause more significant pathology in younger hosts as their brains are still developing. This experiment asked how central nervous system (CNS) viral-infections affect the development of synapses in the pediatric brain during infection and post-infection. Synaptogenesis is at its peak in pediatric mice (10 days old) and we hypothesized that a neurotropic infection could disrupt synaptic proteins. We used a transgenic mouse model where measles virus (MV) infects only mature neurons, leading us to question whether synapses were impacted. We examined synaptic markers in the cerebellum and hippocampus in MV-infected and uninfected mice 9 days and 90 …

Interaction Of High-Fat Diet And Brain Trauma Alters Adipose Tissue Macrophages And Brain Microglia Associated With Exacerbated Cognitive Dysfunction, Rebecca J Henry, James P Barrett, Maria Vaida, Niaz Z Khan, Oleg Makarevich, Rodney M Ritzel, Alan I Faden, Bogdan A Stoica

Faculty, Staff and Student Publications

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular …

Identifying Covariate-Related Subnetworks For Whole-Brain Connectome Analysis, Shuo Chen, Yuan Zhang, Qiong Wu, Chuan Bi, Peter Kochunov, L Elliot Hong

Faculty, Staff and Student Publications

Whole-brain connectome data characterize the connections among distributed neural populations as a set of edges in a large network, and neuroscience research aims to systematically investigate associations between brain connectome and clinical or experimental conditions as covariates. A covariate is often related to a number of edges connecting multiple brain areas in an organized structure. However, in practice, neither the covariate-related edges nor the structure is known. Therefore, the understanding of underlying neural mechanisms relies on statistical methods that are capable of simultaneously identifying covariate-related connections and recognizing their network topological structures. The task can be challenging because of false-positive …

Sarin-Induced Neuroinflammation In Mouse Brain Is Attenuated By The Caspase Inhibitor Q-Vd-Oph, Ekta J. Shah, William C. Grunwald Jr., Teresa L. Garrett, Thomas L. Brown, David R. Cool

Neuroscience, Cell Biology & Physiology Faculty Publications

Organophosphates cause hyperstimulation of the central nervous system, leading to extended seizures, convulsions, and brain damage. Sarin is a highly toxic organophosphate nerve agent that has been employed in several terrorist attacks. The prolonged toxicity of sarin may be enhanced by the neuroinflammatory response initiated by the inflammasome, caspase involvement, and generation/release of proinflammatory cytokines. Since neurodegeneration and neuroinflammation are prevalent in sarin-exposed animals, we were interested in evaluating the capacity of quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone (Q-VD-OPh), a pan caspase inhibitor to attenuate neuroinflammation following sarin exposure. To test this hypothesis, sarin-exposed C57BL/6 mice were treated with Q-VD-OPh or negative control quinolyl-valyl-O-methylglutamyl-[-2,6-difluorophenoxy]-methyl …

Anesthetized Animal Experiments For Neuroscience Research, Shin Nagayama, Sanae Hasegawa-Ishii, Shu Kikuta

Faculty, Staff and Student Publications

Brain research has progressed with anesthetized animal experiments for a long time. Recent progress in research techniques allows us to measure neuronal activity in awake animals combined with behavioral tasks. The trends became more prominent in the last decade. This new research style triggers the paradigm shift in the research of brain science, and new insights into brain function have been revealed. It is reasonable to consider that awake animal experiments are more ideal for understanding naturalistic brain function than anesthetized ones. However, the anesthetized animal experiment still has advantages in some experiments. To take advantage of the anesthetized animal …

Drivers Of Chronic Pathology Following Ischemic Stroke: A Descriptive Review, Grant W Goodman, Trang H Do, Chunfeng Tan, Rodney M Ritzel

Faculty, Staff and Student Publications

Stroke is the third leading cause of death and long-term disability in the world. Considered largely a disease of aging, its global economic and healthcare burden is expected to rise as more people survive into advanced age. With recent advances in acute stroke management, including the expansion of time windows for treatment with intravenous thrombolysis and mechanical thrombectomy, we are likely to see an increase in survival rates. It is therefore critically important to understand the complete pathophysiology of ischemic stroke, both in the acute and subacute stages and during the chronic phase in the months and years following an …

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 …

Cortex-Wide Neural Dynamics Predict Behavioral States And Provide A Neural Basis For Resting-State Dynamic Functional Connectivity, Somayeh Shahsavarani, David N Thibodeaux, Weihao Xu, Sharon H Kim, Fatema Lodgher, Chinwendu Nwokeabia, Morgan Cambareri, Alexis J Yagielski, Hanzhi T Zhao, Daniel A Handwerker, Javier Gonzalez-Castillo, Peter A Bandettini, Elizabeth M C Hillman

Faculty, Staff and Student Publications

Although resting-state functional magnetic resonance imaging (fMRI) studies have observed dynamically changing brain-wide networks of correlated activity, fMRI's dependence on hemodynamic signals makes results challenging to interpret. Meanwhile, emerging techniques for real-time recording of large populations of neurons have revealed compelling fluctuations in neuronal activity across the brain that are obscured by traditional trial averaging. To reconcile these observations, we use wide-field optical mapping to simultaneously record pan-cortical neuronal and hemodynamic activity in awake, spontaneously behaving mice. Some components of observed neuronal activity clearly represent sensory and motor function. However, particularly during quiet rest, strongly fluctuating patterns of activity across …

Tubers Affecting The Fusiform Face Area Are Associated With Autism Diagnosis, Alexander L Cohen, Mallory R Kroeck, Juliana Wall, Peter Mcmanus, Arina Ovchinnikova, Mustafa Sahin, Darcy A Krueger, E Martina Bebin, Hope Northrup, Joyce Y Wu, Simon K Warfield, Jurriaan M Peters, Michael D Fox, Acern Study Group

Faculty, Staff and Student Publications

OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms.

METHODS: We delineated tuber locations for 115 TSC participants with ASD (n = 31) and without ASD (n = 84) from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network. We tested for associations between ASD diagnosis and tuber burden within the whole brain, specific lobes, and at 8 regions of interest derived from the ASD neuroimaging literature, including the anterior …

Markers Of Neuroinflammatory And Degenerative Processes In Professional Athletes With Traumatic Encephalopathy Syndrome, Brooke Conway Kleven

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: The clinical criteria for Traumatic encephalopathy syndrome (ccTES) were developed to improve the diagnosis of Chronic traumatic encephalopathy (CTE). This study aimed to determine whether there was an association between a clinical diagnosis of Traumatic encephalopathy syndrome (TES) and changes in serum biomarkers, balance, neuroimaging, and cognition among athletes in the Professional Athletes Brain Health Study (PABHS).Methods: Of the cohort, 130 professional fighters met age or retirement criteria and went to a consensus conference, with 52 fighters (40%) meeting the criteria for TES. A generalized linear model with generalized estimating equations was utilized to assess the odds of disease …

Comparison Of Brain Nicotine Uptake From Electronic Cigarettes And Combustible Cigarettes, Yantao Zuo, Alexey G Mukhin, Hannah Berg, Janiece D Morgan, Akiva Mintz, Jed E Rose, Kiran Kumar Solingapuram Sai

Faculty, Staff and Student Publications

Brain accumulation rate and magnitude are critical for the acute reinforcing effects of nicotine. Despite electronic cigarettes’ (E-cigs) appeal as substitutes for traditional combustible cigarettes (C-cigs), brain nicotine accumulation (BNA) from E-cigs has not been compared with that from C-cigs using a within-subjects design. BNA was directly assessed with 16 adult dual users (10 females) of E-cigs (e-liquid pH 9.4) and C-cigs, using 11C-nicotine and positron emission tomography (PET). Participants went through two 15-min head scanning sessions during which they inhaled a single puff of E-cig vapor or C-cig smoke containing 11C-nicotine in a randomized order. A full-body scan was …

Ciliogenesis Mechanisms Mediated By Pak2-Arl13b Signaling In Brain Endothelial Cells Is Responsible For Vascular Stability, Karthikeyan Thirugnanam, Shubhangi Prabhudesai, Emma Van Why, Amy Pan, Ankan Gupta, Koji Foreman, Rahima Zennadi, Kevin R. Rarick, Surya M. Nauli, Sean P. Palacek, Ramani Ramchandran

Pharmacy Faculty Articles and Research

In the developing vasculature, cilia, microtubule-based organelles that project from the apical surface of endothelial cells (ECs), have been identified to function cell autonomously to promote vascular integrity and prevent hemorrhage. To date, the underlying mechanisms of endothelial cilia formation (ciliogenesis) are not fully understood. Understanding these mechanisms is likely to open new avenues for targeting EC-cilia to promote vascular stability. Here, we hypothesized that brain ECs ciliogenesis and the underlying mechanisms that control this process are critical for brain vascular stability. To investigate this hypothesis, we utilized multiple approaches including developmental zebrafish model system and primary cell culture systems. …

Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar

Journal of Wellness

The essential question of the relationship between consciousness and matter is ignored in medical school curricula, leading to a machine-like view of the human being that contributes to physician burnout and intellectual dissatisfaction. The evidence suggesting that the brain may not be the seat of consciousness is generally ignored to preserve the worldview of the primacy of matter. By investigating new frameworks detailing the nature of consciousness at different levels of hierarchy, we can bring intellectual rigor to a once opaque subject that supports a fundamental reality about our experience: We are human beings, not only human bodies.

Neurophysiology Of Space Medicine: A Literature Review, Jose R. Velasquez

MEDI 9331 Scholarly Activities Clinical Years

Space medicine is becoming an essential and expanding clinical discipline. Acquiring a deeper and complete picture understanding of the multi-systemic response due to space on human health and function is essential to ensure the success of future space exploration. A comprehensive review of the literature was performed using PubMed and focused on the current neurophysiologic findings of the central nervous system’s response to space. Ground-based analogues, which mimic the effects of microgravity, and actual spaceflight studies have been used to analyze these physiologic adaptations to space. Overall, cerebellar, sensorimotor and vestibular brain regions seem to be affected the most. Through …

Open Neuroscience Initiative, Austin Lim

College of Science and Health Full Text Publications

The Open Neuroscience Initiative is a free-to-use textbook

This project began as a means to overcoming the financial burden that face undergraduate neuroscience students when buying textbooks. By compiling and writing a completely free-to-access textbook that covers the foundations of a typical college introduction to neuroscience course, students would have one less obstacle to overcome in their educational career, allowing them to focus their valuable time and attention on learning rather than finances. To make this project a reality, I began with a humble tweet in May 2019 that managed to gain a tiny bit of traction among the neuroscience …

Amidated Dopamine Neuron Stimulating Peptides For Cns Dopaminergic Upregulation, Luke H. Bradley, Don M. Gash, Greg A. Gerhardt

Neuroscience Faculty Patents

The present invention relates to novel proteins, referred to herein as amidated glial cell line-derived neurotrophic factor (GDNF) peptides (or "Amidated Dopamine Neuron Stimulating peptides (ADNS peptides)"), that are useful for treating brain diseases and injuries that result in dopaminergic deficiencies.

An Examination Into The Relationship Between Iron Deficiency And Postpartum Depression, Sara A. Burroughs

Senior Honors Theses

Postpartum depression is recognized as the most common complication of childbearing; however, its etiology remains fairly undetermined. Many different influences have been hypothesized as to what may cause postpartum depression, including changes in levels of various hormones (such as estrogen and progesterone), a decrease in serotonin, low levels of vitamin D, social factors, and iron deficiency. The lack of strong evidence for one specific cause makes it fairly clear that there are many factors that play a role in the development of postpartum depression. Iron deficiency is one issue that is thought to contribute to the development of postpartum depression …

The Relationship Between Lexical Performance And Regional Gray Matter Volumes: A Longitudinal Study Of Cognitively Healthy Elderly, Jungmoon Hyun

Dissertations, Theses, and Capstone Projects

This study investigated the longitudinal relationship among aging, performance on lexical tasks, and regional gray matter volumes over 2-7 years. A total of 137 older participants who remained cognitively normal were administered four lexical tasks at each time point: the Boston Naming Test (BNT), Vocabulary Test, Semantic- and Phonemic-Fluency task. In addition, they underwent repeated magnetic resonance imaging (MRI) scanning acquired within two months of the lexical tasks. The average interval between time points was 2.36 years (range 1.50-7.64) and the average number of time points was 2.65 times (range 2-5).

Results indicated that age differentially affects lexical task performance …

Exposure To Kynurenic Acid During Adolescence Increases Sign-Tracking And Impairs Long-Term Potentiation In Adulthood, Nicole E. Deangeli, Travis P. Todd, Stephen E. Chang, Hermes H. Yeh, Pamela W. Yeh, David J. Bucci

Dartmouth Scholarship

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and …

Retinal Vascular Biomarkers For Early Detection And Monitoring Of Alzheimer's Disease, Shawn Frost, Yogi Kanagasingam, Hamid Sohrabi, J Vignarajan, P Bourgeat, Olivier Salvado, Victor Villemagne, Christopher Rowe, S Lance Macaulay, Cassandra Szoeke, Kathryn A. Ellis, David Ames, Colin L. Masters, Stephanie Rainey-Smith, Ralph N. Martins

Research outputs 2013

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes …

White Matter Diffusion Alterations In Normal Women At Risk Of Alzheimer's Disease, Charles D. Smith, Himachandra Chebrolu, Anders H. Andersen, David A. Powell, Mark A. Lovell, Shuling Xiong, Brian T. Gold

Neurology Faculty Publications

Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal …

Acat1 Gene Ablation Increases 24(S)-Hydroxycholesterol Content In The Brain And Ameliorates Amyloid Pathology In Mice With Ad, Elena Y. Bryleva, Maximillian A. Rogers, Catherine C. Y. Chang, Floyd Buen

Dartmouth Scholarship

Cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative diseases, including the abnormal accumulation of amyloid-beta, one of the pathological hallmarks of Alzheimer disease (AD). Acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) are two enzymes that convert free cholesterol to cholesteryl esters. ACAT inhibitors have recently emerged as promising drug candidates for AD therapy. However, how ACAT inhibitors act in the brain has so far remained unclear. Here we show that ACAT1 is the major functional isoenzyme in the mouse brain. ACAT1 gene ablation (A1-) in triple transgenic (i.e., 3XTg-AD) mice leads to more than 60% reduction in full-length human …

Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima

Department of Biochemistry and Molecular Biology Faculty Papers

The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …

Abeta42 Mutants With Different Aggregation Profiles Induce Distinct Pathologies In Drosophila., Koichi Iijima, Hsueh-Cheng Chiang, Stephen A Hearn, Inessa Hakker, Anthony Gatt, Christopher Shenton, Linda Granger, Amy Leung, Kanae Iijima-Ando, Yi Zhong

Department of Biochemistry and Molecular Biology Faculty Papers

Aggregation of the amyloid-beta-42 (Abeta42) peptide in the brain parenchyma is a pathological hallmark of Alzheimer's disease (AD), and the prevention of Abeta aggregation has been proposed as a therapeutic intervention in AD. However, recent reports indicate that Abeta can form several different prefibrillar and fibrillar aggregates and that each aggregate may confer different pathogenic effects, suggesting that manipulation of Abeta42 aggregation may not only quantitatively but also qualitatively modify brain pathology. Here, we compare the pathogenicity of human Abeta42 mutants with differing tendencies to aggregate. We examined the aggregation-prone, EOFAD-related Arctic mutation (Abeta42Arc) and an artificial mutation (Abeta42art) that …

Role For Akt3/Protein Kinase Bγ In Attainment Of Normal Brain Size, Rachel M. Easton, Han Cho, Kristin Roovers, Diana W. Shineman

Dartmouth Scholarship

Studies of Drosophila and mammals have revealed the importance of insulin signaling through phosphatidylinositol 3-kinase and the serine/threonine kinase Akt/protein kinase B for the regulation of cell, organ, and organismal growth. In mammals, three highly conserved proteins, Akt1, Akt2, and Akt3, comprise the Akt family, of which the first two are required for normal growth and metabolism, respectively. Here we address the function of Akt3. Like Akt1, Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. However, in contrast to Akt1^−/− mice, which display a …

Global Cns Gene Transfer For A Childhood Neurogenetic Enzyme Deficiency: Canavan Disease., Paola Leone, Christopher G Janson, Scott J Mcphee, Matthew J During

Department of Neurosurgery Faculty Papers

The neurogenetic prototypic disease on which we chose to test our gene therapy strategy is Canavan disease (CD). CD is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. At present the disease is uniformly fatal in affected probands. CD is characterized by mutations in the aspartoacylase (ASPA) gene, resulting in loss of enzyme activity. In this review, recent evidence is summarized on the etiology and possible treatments for CD. In particular, we discuss two gene delivery systems representing recent advances in both viral and liposome technology: a novel cationic liposome-polymer-DNA (LPD) complex, DCChol/DOPE-protamine, as well as recombinant …